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Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

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Casey, Kenneth L.

1999-07-01

Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.
Modeling Parkinson’s Disease Falls Associated With Brainstem Cholinergic Systems Decline

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Kucinski, Aaron; Sarter, Martin

2015-01-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson’s disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from t...
A probabilistic atlas of human brainstem pathways based on connectome imaging data.

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Tang, Yuchun; Sun, Wei; Toga, Arthur W; Ringman, John M; Shi, Yonggang

2018-04-01

The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles
The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention.

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Forte, Antonio Elia; Etard, Octave; Reichenbach, Tobias

2017-10-10

Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention.
Characterising Ageing in the Human Brainstem Using Quantitative Multimodal MRI Analysis

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Christian eLambert

2013-08-01

Full Text Available Ageing is ubiquitous to the human condition. The MRI correlates of healthy ageing have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI and DTI. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analysing this region. By utilising a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of ageing within the human brainstem in vivo. Using quantitative MRI (qMRI, tensor based morphometry (TBM and voxel based quantification (VBQ, the volumetric and quantitative changes across healthy adults between 19-75 years were characterised. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetric loss of the brachium conjunctivum, with a corresponding decrease in magnetisation transfer (MT and increase in proton density (PD, accounting for the previously described midbrain shrinkage. Additionally, we found increases in R1 and PD in several pontine and medullary structures. We consider these changes in the context of well-characterised, functional age-related changes, and propose potential biophysical mechanisms. This study provides detailed quantitative analysis of the internal architecture of the brainstem and provides a baseline for further studies of neurodegenerative diseases that are characterised by early, pre-clinical involvement of the brainstem, such as Parkinson’s and Alzheimer’s diseases.
Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

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de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

2017-11-15

The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1 H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.
[Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

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Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

2012-04-01

To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.
Arterial territories of human brain: brainstem and cerebellum

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Tatu, L.; Moulin, T.; Bogousslavsky, J.; Duvernoy, H.

1997-01-01

The development of neuroimaging has allowed clinicians to improve clinico-anatomic correlations in patients with strokes. Brainstem and cerebellum structures are well delineated on MRI, but there is a lack of standardization in their arterial supply. We present a system of 12 brainstem and cerebellum axial sections, depicting the dominant arterial territories and the most important anatomic structures. These sections may be used as a practical tool to determine arterial territories on MRI, and may help establish consistent clinico-anatomic correlations in patients with brainstem and cerebellar ischemic strokes. (authors)
Dissociating basal forebrain and medial temporal amnesic syndromes: insights from classical conditioning.

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Myer, Catherine E; Bryant, Deborah; DeLuca, John; Gluck, Mark A

2002-01-01

In humans, anterograde amnesia can result from damage to the medial temporal (MT) lobes (including hippocampus), as well as to other brain areas such as basal forebrain. Results from animal classical conditioning studies suggest that there may be qualitative differences in the memory impairment following MT vs. basal forebrain damage. Specifically, delay eyeblink conditioning is spared after MT damage in animals and humans, but impaired in animals with basal forebrain damage. Recently, we have likewise shown delay eyeblink conditioning impairment in humans with amnesia following anterior communicating artery (ACoA) aneurysm rupture, which damages the basal forebrain. Another associative learning task, a computer-based concurrent visual discrimination, also appears to be spared in MT amnesia while ACoA amnesics are slower to learn the discriminations. Conversely, animal and computational models suggest that, even though MT amnesics may learn quickly, they may learn qualitatively differently from controls, and these differences may result in impaired transfer when familiar information is presented in novel combinations. Our initial data suggests such a two-phase learning and transfer task may provide a double dissociation between MT amnesics (spared initial learning but impaired transfer) and ACoA amnesics (slow initial learning but spared transfer). Together, these emerging data suggest that there are subtle but dissociable differences in the amnesic syndrome following damage to the MT lobes vs. basal forebrain, and that these differences may be most visible in non-declarative tasks such as eyeblink classical conditioning and simple associative learning.
Directed differentiation of basal forebrain cholinergic neurons from human pluripotent stem cells.

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Hu, Yao; Qu, Zhuang-Yin; Cao, Shi-Ying; Li, Qi; Ma, Lixiang; Krencik, Robert; Xu, Min; Liu, Yan

2016-06-15

Basal forebrain cholinergic neurons (BFCNs) play critical roles in learning, memory and cognition. Dysfunction or degeneration of BFCNs may connect to neuropathology, such as Alzheimer's disease, Down's syndrome and dementia. Generation of functional BFCNs may contribute to the studies of cell-based therapy and pathogenesis that is related to learning and memory deficits. Here we describe a detail method for robust generation of BFCNs from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). In this method, BFCN progenitors are patterned from hESC or hiPSC-derived primitive neuroepithelial cells, with the treatment of sonic hedgehog (SHH) or combination with its agonist Purmorphamine, and by co-culturing with human astrocytes. At day 20, ∼90% hPSC-derived progenitors expressed NKX2.1, which is a transcriptional marker for MGE. Moreover, around 40% of NKX2.1+ cells co-expressed OLIG2 and ∼15% of NKX2.1+ cells co-expressed ISLET1, which are ventral markers. At day 35, ∼40% neurons robustly express ChAT, most of which are co-labeled with NKX2.1, ISLET1 and FOXG1, indicating the basal forebrain-like identity. At day 45, these neurons express mature neuronal markers MAP2, Synapsin, and VAChT. In this method, undefined conditions including genetic modification or cell-sorting are avoided. As a choice, feeder free conditions are used to avoid ingredients of animal origin. Moreover, Purmorphamine can be substituted for SHH to induce ventral progenitors effectively and economically. We provide an efficient method to generate BFCNs from multiple hPSC lines, which offers the potential application for disease modeling and pharmacological studies. Copyright © 2016 Elsevier B.V. All rights reserved.
Challenge-driven attention: interacting frontal and brainstem systems

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Rajeev D S Raizada

2008-03-01

Full Text Available The world is an unpredictable place, presenting challenges that fl uctuate from moment to moment. However, the neural systems for responding to such challenges are far from fully understood. Using fMRI, we studied an audiovisual task in which the trials' diffi culty and onset times varied unpredictably. Two regions were found to increase their activation for challenging trials, with their activities strongly correlated: right frontal cortex and the brainstem. The frontal area matched regions found in previous human studies of cognitive control, and activated in a graded manner with increasing task diffi culty. The brainstem responded only to the most diffi cult trials, showing a phasic activity pattern paralleling locus coeruleus recordings in monkeys. These results reveal a bridge between animal and human studies, and suggest interacting roles for the brainstem and right frontal cortex: the brainstem may signal that an attentional challenge is occurring, while right frontal cortex allocates cognitive resources in response.
Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

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Dimitri Ryczko

2017-05-01

Full Text Available In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease.
Disconnection of the Ascending Arousal System in Traumatic Coma

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Edlow, Brian L.; Haynes, Robin L.; Takahashi, Emi; Klein, Joshua P.; Cummings, Peter; Benner, Thomas; Greer, David M.; Greenberg, Steven M.; Wu, Ona; Kinney, Hannah C.; Folkerth, Rebecca D.

2013-01-01

Traumatic coma is associated with disruption of axonal pathways throughout the brain but the specific pathways involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging (HARDI) to map the connectivity of axonal pathways that mediate the 2 critical components of consciousness – arousal and awareness – in the postmortem brain of a 62-year-old woman with acute traumatic coma and in 2 control brains. HARDI tractography guided tissue sampling in the neuropathological analysis. HARDI tractography demonstrated complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei. In contrast, hemispheric arousal pathways connecting the thalamus and basal forebrain to the cerebral cortex were only partially disrupted, as were the cortical “awareness pathways.” Neuropathologic examination, which utilized β-amyloid precursor protein and fractin immunomarkers, revealed axonal injury in the white matter of the brainstem and cerebral hemispheres that corresponded to sites of HARDI tract disruption. Axonal injury was also present within the grey matter of the hypothalamus, thalamus, basal forebrain, and cerebral cortex. We propose that traumatic coma may be a subcortical disconnection syndrome related to the disconnection of specific brainstem arousal nuclei from the thalamus and basal forebrain. PMID:23656993
Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

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Hakuba Nobuhiro

2010-09-01

Full Text Available Abstract Background Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia. Results Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia, 1 d, 3 d and 7 d (n = 4 in each group. Sham-operated animals (n = 4 were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2. Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1-positive cells were detected in the same areas in all animals. Conclusion These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.
Catecholamine function, brain state dynamics, and human cognition

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Van den Brink R.L.,

2017-01-01

The locus coeruleus (LC) is a nucleus in the brainstem, and projects widely to the forebrain where it releases norepinephrine (NE). Catecholamines such as NE do not have a unitary effect on their target neurons, but instead influence the function of other neurotransmitters, a process that is known
Of mice, birds, and men: the mouse ultrasonic song system has some features similar to humans and song-learning birds.

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Gustavo Arriaga

Full Text Available Humans and song-learning birds communicate acoustically using learned vocalizations. The characteristic features of this social communication behavior include vocal control by forebrain motor areas, a direct cortical projection to brainstem vocal motor neurons, and dependence on auditory feedback to develop and maintain learned vocalizations. These features have so far not been found in closely related primate and avian species that do not learn vocalizations. Male mice produce courtship ultrasonic vocalizations with acoustic features similar to songs of song-learning birds. However, it is assumed that mice lack a forebrain system for vocal modification and that their ultrasonic vocalizations are innate. Here we investigated the mouse song system and discovered that it includes a motor cortex region active during singing, that projects directly to brainstem vocal motor neurons and is necessary for keeping song more stereotyped and on pitch. We also discovered that male mice depend on auditory feedback to maintain some ultrasonic song features, and that sub-strains with differences in their songs can match each other's pitch when cross-housed under competitive social conditions. We conclude that male mice have some limited vocal modification abilities with at least some neuroanatomical features thought to be unique to humans and song-learning birds. To explain our findings, we propose a continuum hypothesis of vocal learning.
Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: a case study at 11.7 T.

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Aggarwal, Manisha; Zhang, Jiangyang; Pletnikova, Olga; Crain, Barbara; Troncoso, Juan; Mori, Susumu

2013-07-01

A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125-255 μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7 T. The DTI data revealed microscopic neuroanatomical details, allowing three-dimensional visualization and reconstruction of fiber pathways including the decussation of the pyramidal tract fibers, and interdigitating fascicles of the corticospinal and transverse pontine fibers. Additionally, strong gray-white matter contrasts in the apparent diffusion coefficient (ADC) maps enabled precise delineation of gray matter nuclei in the brainstem, including the cranial nerve and the inferior olivary nuclei. Comparison with myelin-stained histology shows that at the level of resolution achieved in this study, the structural details resolved with DTI contrasts in the brainstem were comparable to anatomical delineation obtained with histological sectioning. Major neural structures delineated from DTI contrasts in the brainstem are segmented and three-dimensionally reconstructed. Further, the ex vivo DTI data are nonlinearly mapped to a widely-used in vivo human brain atlas, to construct a high-resolution atlas of the brainstem in the Montreal Neurological Institute (MNI) stereotaxic coordinate space. The results demonstrate the feasibility of developing a 3D DTI based atlas for detailed characterization of brainstem neuroanatomy with high resolution and contrasts, which will be a useful resource for research and clinical applications. Copyright © 2013 Elsevier Inc. All rights reserved.
The human premotor oculomotor brainstem system - can it help to understand oculomotor symptoms in Huntington's disease?

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Rueb, U.; Heinsen, H.; Brunt, E. R.; Landwehrmeyer, B.; Den Dunnen, W. F. A.; Gierga, K.; Deller, T.

Recent progress in oculomotor research has enabled new insights into the functional neuroanatomy of the human premotor oculomotor brainstem network. In the present review, we provide an overview of its functional neuroanatomy and summarize the broad range of oculomotor dysfunctions that may occur in
Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

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Alexandre Lehmann

Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.
Somatotopic Arrangement and Location of the Corticospinal Tract in the Brainstem of the Human Brain

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Jang, Sung Ho

2011-01-01

The corticospinal tract (CST) is the most important motor pathway in the human brain. Detailed knowledge of CST somatotopy is important in terms of rehabilitative management and invasive procedures for patients with brain injuries. In this study, I conducted a review of nine previous studies of the somatotopical location and arrangement at the brainstem in the human brain. The results of this review indicated that the hand and leg somatotopies of the CST are arranged medio-laterally in the mi...

Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

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Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

2014-09-01

Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.
In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

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Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

2016-06-01

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.
Giant tubercular brainstem abscess: A case report

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Pragati Chigurupati

2014-01-01

Full Text Available Tubercular brain abscesses are uncommon and tubercular brainstem abscesses are rarely reported. Most of these cases occur in immunocompromised patients. We report a case of giant brainstem abscess in a 5-year-old human immunodeficiency virus-seronegative female child who presented with complaints of headache, diplopia and unsteadiness of gait since 6 months. Diagnosis was made by a magnetic resonance imaging scan of brain. The patient demonstrated a remarkable clinical recovery after microsurgery combined with a course of antituberculous therapy. Microbiological and histological findings confirmed the diagnosis of a tuberculous abscess.
MR findings of brainstem injury

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Park, Man Soo; Hwang, Woo Cheol; Park, Choong Ki [Hallym University College of Medicine, Seoul (Korea, Republic of); Suh, Dae Chul [University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang Joon [Dankook University of College of Medicine, Cheonan (Korea, Republic of)

1995-02-15

To analyze the characteristics of traumatic brainstem injury by CT and MR. CT and MR studies of 10 patients with traumatic brainstem lesion in MR were retrospectively reviewed, particularly attended to location, signal intensity and associated lesions. CT failed to depict 8 of 10 brainstem lesions. All lesions were detected in MR images with T2-weighted images showing higher detection rate (n = 10) (100%) than T1-weighted images (n = 3) (30%) or CT (n = 2) (20%). The brainstem lesions located in the dorsolateral aspects of the rostral brainstem (mid brain and upper pons) in 7 (70%) cases, in ventral aspects of rostral brain in 2 (20%) cases and in median portion of pons in 1 (10%) case. Corpus callosal (n = 5), lobar white matter (n = 5) diffuse axonal injury, and 2 hemorrhagic lesions in basal ganglia were the associated findings. MR imaging is more helpful than CT in the detection of brainstem injury, especially T2 weighted images. Primary brainstem lesions were typically located in the dorsolateral aspect of rostral brainstem (midbrain and upper pons). Corpus callosum and white matter lesions were frequently associated.
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File list: His.Neu.50.AllAg.Forebrain [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.50.AllAg.Forebrain mm9 Histone Neural Forebrain SRX093315,SRX377672,SRX3776...70,SRX377678,SRX377676,SRX093314,SRX377674 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Forebrain.bed ...
File list: His.Neu.10.AllAg.Forebrain [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.10.AllAg.Forebrain mm9 Histone Neural Forebrain SRX093315,SRX377672,SRX3776...70,SRX377678,SRX377676,SRX093314,SRX377674 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Forebrain.bed ...
File list: His.Neu.05.AllAg.Forebrain [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.05.AllAg.Forebrain mm9 Histone Neural Forebrain SRX093315,SRX377678,SRX3776...72,SRX377670,SRX377676,SRX377674,SRX093314 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Forebrain.bed ...
A brainstem anosognosia of hemiparesis

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Kazuo Abe

2009-10-01

Full Text Available A woman had anosognosia for hemiplegia as a manifestation of brainstem infarction. She had no mental or neuropsychological disturbances, and had involvement of the brainstem in the frontal/parietal-subcortical circuits to the right cerebral hemisphere. Brainstem lesions that disrupt frontal/parietal-subcortical areas may affect anosognosia for hemiplegia.
Brainstem evoked potentials in infantile spasms

International Nuclear Information System (INIS)

Miyazaki, Masahito; Hashimoto, Toshiaki; Murakawa, Kazuyoshi; Tayama, Masanobu; Kuroda, Yasuhiro

1992-01-01

In ten patients with infantile spasms, brainstem evoked potentials and MRI examinations were performed to evaluate the brainstem involvement. The result of short latency somatosensory evoked potentials (SSEP) following the right median nerve stimulation revealed abnormal findings including the absence or low amplitudes of the waves below wave P3 and delayed central conduction time in 7 of the ten patients. The result of auditory brainstem responses (ABR) revealed abnormal findings including low amplitudes of wave V, prolonged interpeak latency of waves I-V and absence of the waves below wave IV in 5 of the ten patients. The result of the MRI examinations revealed various degrees of the brainstem atrophy in 6 of the ten patients, all of whom showed abnormal brainstem evoked potentials. The result of this study demonstrates that patients with infantile spasms are frequently associated with brainstem dysfunction and raises the possibility that brainstem atrophy might be a cause of infantile spasms. (author)
Large-scale synchronized activity in the embryonic brainstem and spinal cord

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Yoko eMomose-Sato

2013-04-01

Full Text Available In the developing central nervous system, spontaneous activity appears well before the brain responds to external sensory inputs. One of the earliest activities is observed in the hindbrain and spinal cord, which is detected as rhythmic electrical discharges of cranial and spinal motoneurons or oscillations of Ca2+- and voltage-related optical signals. Shortly after the initial expression, the spontaneous activity appearing in the hindbrain and spinal cord exhibits a large-scale correlated wave that propagates over a wide region of the central nervous system, maximally extending to the lumbosacral cord and to the forebrain. In this review, we describe several aspects of this synchronized activity by focusing on the basic properties, development, origin, propagation pattern, pharmacological characteristics, and possible mechanisms underlying the generation of the activity. These profiles differ from those of the respiratory and locomotion pattern generators observed in the mature brainstem and spinal cord, suggesting that the wave is primordial activity that appears during a specific period of embryonic development and plays some important roles in the development of the central nervous system.
ESC-Derived Basal Forebrain Cholinergic Neurons Ameliorate the Cognitive Symptoms Associated with Alzheimer’s Disease in Mouse Models

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Wei Yue

2015-11-01

Full Text Available Degeneration of basal forebrain cholinergic neurons (BFCNs is associated with cognitive impairments of Alzheimer’s disease (AD, implying that BFCNs hold potentials in exploring stem cell-based replacement therapy for AD. However, studies on derivation of BFCNs from embryonic stem cells (ESCs are limited, and the application of ESC-derived BFCNs remains to be determined. Here, we report on differentiation approaches for directing both mouse and human ESCs into mature BFCNs. These ESC-derived BFCNs exhibit features similar to those of their in vivo counterparts and acquire appropriate functional properties. After transplantation into the basal forebrain of AD model mice, ESC-derived BFCN progenitors predominantly differentiate into mature cholinergic neurons that functionally integrate into the endogenous basal forebrain cholinergic projection system. The AD mice grafted with mouse or human BFCNs exhibit improvements in learning and memory performances. Our findings suggest a promising perspective of ESC-derived BFCNs in the development of stem cell-based therapies for treatment of AD.
A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

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Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

2015-04-29

Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.
Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

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Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

2017-11-17

The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
File list: InP.Neu.20.AllAg.Forebrain [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: InP.Neu.10.AllAg.Forebrain [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Neu.10.AllAg.Forebrain mm9 Input control Neural Forebrain SRX377679,SRX669236,S...RX377677,SRX377675,SRX377673,SRX377671 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.10.AllAg.Forebrain.bed ...

File list: InP.Neu.50.AllAg.Forebrain [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Neu.50.AllAg.Forebrain mm9 Input control Neural Forebrain SRX377679,SRX377675,S...RX377677,SRX377673,SRX669236,SRX377671 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.50.AllAg.Forebrain.bed ...
Microglia Modulate Wiring of the Embryonic Forebrain

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Paola Squarzoni

2014-09-01

Full Text Available Dysfunction of microglia, the tissue macrophages of the brain, has been associated with the etiology of several neuropsychiatric disorders. Consistently, microglia have been shown to regulate neurogenesis and synaptic maturation at perinatal and postnatal stages. However, microglia invade the brain during mid-embryogenesis and thus could play an earlier prenatal role. Here, we show that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits. Using multiple mouse models, including cell-depletion approaches and cx3cr1−/−, CR3−/−, and DAP12−/− mutants, we find that perturbing microglial activity affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons. Since defects in both dopamine innervation and cortical networks have been linked to neuropsychiatric diseases, our study provides insights into how microglial dysfunction can impact forebrain connectivity and reveals roles for immune cells during normal assembly of brain circuits.
Forebrain neurogenesis: From embryo to adult.

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Dennis, Daniel; Picketts, David; Slack, Ruth S; Schuurmans, Carol

2016-01-01

A satellite symposium to the Canadian Developmental Biology Conference 2016 was held on March 16-17, 2016 in Banff, Alberta, Canada, entitled Forebrain Neurogenesis : From embryo to adult . The Forebrain Neurogenesis symposium was a focused, high-intensity meeting, bringing together the top Canadian and international researchers in the field. This symposium reported the latest breaking news, along with 'state of the art' techniques to answer fundamental questions in developmental neurobiology. Topics covered ranged from stem cell regulation to neurocircuitry development, culminating with a session focused on neuropsychiatric disorders. Understanding the underlying causes of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) is of great interest as diagnoses of these conditions are climbing at alarming rates. For instance, in 2012, the Centers for Disease Control reported that the prevalence rate of ASD in the U.S. was 1 in 88; while more recent data indicate that the number is as high as 1 in 68 (Centers for Disease Control and Prevention MMWR Surveillance Summaries. Vol. 63. No. 2). Similarly, the incidence of ASD is on the rise in Canada, increasing from 1 in 150 in 2000 to 1 in 63 in 2012 in southeastern Ontario (Centers for Disease Control and Prevention). Currently very little is known regarding the deficits underlying these neurodevelopmental conditions. Moreover, the development of effective therapies is further limited by major gaps in our understanding of the fundamental processes that regulate forebrain development and adult neurogenesis. The Forebrain Neurogenesis satellite symposium was thus timely, and it played a key role in advancing research in this important field, while also fostering collaborations between international leaders, and inspiring young researchers.
Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

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Anne J Blood

Full Text Available There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.
Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons

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Phillips, H.S.; Hains, J.M.; Laramee, G.R.; Rosenthal, A.; Winslow, J.W. (Genentech, San Francisco, CA (USA))

1990-10-12

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) are homologs of the well-known neurotrophic factor nerve growth factor. The three members of this family display distinct patterns of target specificity. To examine the distribution in brain of messenger RNA for these molecules, in situ hybridization was performed. Cells hybridizing intensely to antisense BDNF probe were located throughout the major targets of the rat basal forebrain cholinergic system, that is, the hippocampus, amygdala, and neocortex. Strongly hybridizing cells were also observed in structures associated with the olfactory system. The distribution of NT3 mRNA in forebrain was much more limited. Within the hippocampus, labeled cells were restricted to CA2, the most medial portion of CA1, and the dentate gyrus. In human hippocampus, cells expressing BDNF and mRNA are distributed in a fashion similar to that observed in the rat. These findings point to both basal forebrain cholinergic cells and olfactory pathways as potential central targets for BDNF.
Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons

International Nuclear Information System (INIS)

Phillips, H.S.; Hains, J.M.; Laramee, G.R.; Rosenthal, A.; Winslow, J.W.

1990-01-01

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) are homologs of the well-known neurotrophic factor nerve growth factor. The three members of this family display distinct patterns of target specificity. To examine the distribution in brain of messenger RNA for these molecules, in situ hybridization was performed. Cells hybridizing intensely to antisense BDNF probe were located throughout the major targets of the rat basal forebrain cholinergic system, that is, the hippocampus, amygdala, and neocortex. Strongly hybridizing cells were also observed in structures associated with the olfactory system. The distribution of NT3 mRNA in forebrain was much more limited. Within the hippocampus, labeled cells were restricted to CA2, the most medial portion of CA1, and the dentate gyrus. In human hippocampus, cells expressing BDNF and mRNA are distributed in a fashion similar to that observed in the rat. These findings point to both basal forebrain cholinergic cells and olfactory pathways as potential central targets for BDNF
Air pollution is associated with brainstem auditory nuclei pathology and delayed brainstem auditory evoked potentials.

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Calderón-Garcidueñas, Lilian; D'Angiulli, Amedeo; Kulesza, Randy J; Torres-Jardón, Ricardo; Osnaya, Norma; Romero, Lina; Keefe, Sheyla; Herritt, Lou; Brooks, Diane M; Avila-Ramirez, Jose; Delgado-Chávez, Ricardo; Medina-Cortina, Humberto; González-González, Luis Oscar

2011-06-01

We assessed brainstem inflammation in children exposed to air pollutants by comparing brainstem auditory evoked potentials (BAEPs) and blood inflammatory markers in children age 96.3±8.5 months from highly polluted (n=34) versus a low polluted city (n=17). The brainstems of nine children with accidental deaths were also examined. Children from the highly polluted environment had significant delays in wave III (t(50)=17.038; p7.501; p<0.0001), consisting with delayed central conduction time of brainstem neural transmission. Highly exposed children showed significant evidence of inflammatory markers and their auditory and vestibular nuclei accumulated α synuclein and/or β amyloid(1-42). Medial superior olive neurons, critically involved in BAEPs, displayed significant pathology. Children's exposure to urban air pollution increases their risk for auditory and vestibular impairment. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.
Surgical management of spontaneous hypertensive brainstem hemorrhage

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Bal Krishna Shrestha

2015-09-01

Full Text Available Spontaneous hypertensive brainstem hemorrhage is the spontaneous brainstem hemorrhage associated with long term hypertension but not having definite focal or objective lesion. It is a catastrophic event which has a poor prognosis and usually managed conservatively. It is not uncommon, especially in eastern Asian populations, accounting approximately for 10% of the intracerebral hemorrhage. Before the advent of computed tomography, the diagnosis of brainstem hemorrhage was usually based on the clinical picture or by autopsy and believed to be untreatable via surgery. The introduction of computed tomography permitted to categorize the subtypes of brainstem hemorrhage with more predicted outcome. Continuous ongoing developments in the stereotactic surgery and microsurgery have added more specific surgical management in these patients. However, whether to manage conservatively or promptly with surgical evacuation of hematoma is still a controversy. Studies have shown that an accurate prognostic assessment based on clinical and radiological features on admission is critical for establishing a reasonable therapeutic approach. Some authors have advocate conservative management, whereas others have suggested the efficacy of surgical treatment in brainstem hemorrhage. With the widening knowledge in microsurgical techniques as well as neuroimaging technology, there seems to have more optimistic hope of surgical management of spontaneous hypertensive brainstem hemorrhage for better prognosis. Here we present five cases of severe spontaneous hypertensive brainstem hemorrhage patients who had undergone surgery; and explore the possibilities of surgical management in patients with the spontaneous hypertensive brainstem hemorrhage.
A brainstem variant of reversible posterior leukoencephalopathy syndrome

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Kitaguchi, H.; Tomimoto, H.; Terada, K. [Kyoto University, Department of Neurology, Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Miki, Y.; Yamamoto, A. [Kyoto University, Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Satoi, H.; Kanda, M. [Ijinkai Takeda General Hospital, Department of Neurology, Fushimi-ku, Kyoto (Japan); Fukuyama, H. [Kyoto University, Human Brain Research Center, Graduate School of Medicine, Sakyo-ku, Kyoto (Japan)

2005-09-01

Reversible posterior leukoencephalopathy syndrome (RPLS) is caused by various heterogeneous factors, the commonest being hypertension, followed by nonhypertensive causes such as eclampsia, renal diseases and immunosuppressive therapy. Patients with RPLS exhibit bilateral white and gray matter abnormalities in the posterior aspects of the cerebral hemispheres. However, this syndrome may affect the brainstem predominantly, and these cases are designated as hypertensive brainstem encephalopathy. We present here two patients with reversible brainstem encephalopathy: one with hypertension and the other without hypertension. These patients presented with swelling and diffuse hyperintensities of the brainstem in fluid-attenuated inversion-recovery (FLAIR) and T2-weighted MRI, but with relatively mild clinical symptoms. They recovered without major neurological deficits, but had residual lacunar lesions in the pons. Reversible brainstem encephalopathy with characteristic MRI features was found in both hypertensive and nonhypertensive patients. These patients were diagnosed with a brainstem variant of RPLS, which is potentially fully reversible after an adequate treatment, and therefore should be carefully differentiated from other brainstem disease conditions. (orig.)
A brainstem variant of reversible posterior leukoencephalopathy syndrome

International Nuclear Information System (INIS)

Kitaguchi, H.; Tomimoto, H.; Terada, K.; Miki, Y.; Yamamoto, A.; Satoi, H.; Kanda, M.; Fukuyama, H.

2005-01-01

Reversible posterior leukoencephalopathy syndrome (RPLS) is caused by various heterogeneous factors, the commonest being hypertension, followed by nonhypertensive causes such as eclampsia, renal diseases and immunosuppressive therapy. Patients with RPLS exhibit bilateral white and gray matter abnormalities in the posterior aspects of the cerebral hemispheres. However, this syndrome may affect the brainstem predominantly, and these cases are designated as hypertensive brainstem encephalopathy. We present here two patients with reversible brainstem encephalopathy: one with hypertension and the other without hypertension. These patients presented with swelling and diffuse hyperintensities of the brainstem in fluid-attenuated inversion-recovery (FLAIR) and T2-weighted MRI, but with relatively mild clinical symptoms. They recovered without major neurological deficits, but had residual lacunar lesions in the pons. Reversible brainstem encephalopathy with characteristic MRI features was found in both hypertensive and nonhypertensive patients. These patients were diagnosed with a brainstem variant of RPLS, which is potentially fully reversible after an adequate treatment, and therefore should be carefully differentiated from other brainstem disease conditions. (orig.)
Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline.

Science.gov (United States)

Kucinski, Aaron; Sarter, Martin

2015-04-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging.

Science.gov (United States)

Zhang, Bei; Seifert, Alan C; Kim, Joo-Won; Borrello, Joseph; Xu, Junqian

2017-10-01

Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
Defects in GPI biosynthesis perturb Cripto signaling during forebrain development in two new mouse models of holoprosencephaly

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David M. McKean

2012-07-01

Holoprosencephaly is the most common forebrain defect in humans. We describe two novel mouse mutants that display a holoprosencephaly-like phenotype. Both mutations disrupt genes in the glycerophosphatidyl inositol (GPI biosynthesis pathway: gonzo disrupts Pign and beaker disrupts Pgap1. GPI anchors normally target and anchor a diverse group of proteins to lipid raft domains. Mechanistically we show that GPI anchored proteins are mislocalized in GPI biosynthesis mutants. Disruption of the GPI-anchored protein Cripto (mouse and TDGF1 (human ortholog have been shown to result in holoprosencephaly, leading to our hypothesis that Cripto is the key GPI anchored protein whose altered function results in an HPE-like phenotype. Cripto is an obligate Nodal co-factor involved in TGFβ signaling, and we show that TGFβ signaling is reduced both in vitro and in vivo. This work demonstrates the importance of the GPI anchor in normal forebrain development and suggests that GPI biosynthesis genes should be screened for association with human holoprosencephaly.
MRI findings of multiple sclerosis involving the brainstem

International Nuclear Information System (INIS)

Park, Jeong Hoon; Jeong, Hae Woong; Kim, Hyun Jin; Cho, Jae Kwoeng; Kim, Chang Soo

2001-01-01

To describe MRI findings of multiple sclerosis involving the brainstem. Among 35 cases of clinically definite multiple sclerosis, the authors retrospectively analysed 20 in which the brainstem was involved. MR images were analysed with regard to involvement sites in the brainstem or other locations, signal intensity, multiplicity, shape, enhancement pattern, and contiguity of brainstem lesions with cisternal or ventricular CSF space. The brainstem was the only site of involvement in five cases (25%), while simultaneous involvement of the brainstem and other sites was observed in 15 cases (75%). No case involved only the midbrain or medulla oblongata, and simultaneous involvement of the midbrain, pons and medulla oblongata was noted in 12 cases (60%). The most frequently involved region of the brainstem was the medulla oblongata (n=13; 90%), followed by the pons (n=17; 85%) and the midbrain (n=16; 80%). Compared with normal white matter, brainstem lesions showed low signal intensity on T1 weighted images, and high signal intensity on T2 weighted, proton density weighted, and FLAIR images. In 17 cases (85%), multiple intensity was observed, and the shape of lesions varied: oval, round, elliptical, patchy, crescentic, confluent or amorphous were seen on axial MR images, and in 14 cases (82%), coronal or sagittal scanning showed that lesions were long and tubular. Contiguity between brainstem lesions and cisternal or ventricular CSF space was seen in all cases (100%) involving midbrain (16/16) and medulla oblongata (18/18) and in 15 of 17 (88%) involving the pons. Contrast enhancement was apparent in 7 of 12 cases (58%). In the brainstem, MRI demonstrated partial or total contiguity between lesions and cisternal or ventricular CSF space, and coronal or sagittal images showed that lesions were long and tubuler
Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

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Adam S Hamlin

Full Text Available Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic or uncued (idiothetic recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze, and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.
Forebrain CRF1 Modulates Early-Life Stress-Programmed Cognitive Deficits

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Wang, Xiao-Dong; Rammes, Gerhard; Kraev, Igor; Wolf, Miriam; Liebl, Claudia; Scharf, Sebastian H.; Rice, Courtney J.; Wurst, Wolfgang; Holsboer, Florian; Deussing, Jan M.; Baram, Tallie Z.; Stewart, Michael G.; Müller, Marianne B.; Schmidt, Mathias V.

2012-01-01

Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF1), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF1 knock-out (CRF1-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF1 in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF1 deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF1-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF1 signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity. PMID:21940453
Magnetic resonance imaging in the evaluation of the brainstem

International Nuclear Information System (INIS)

Han, J.S.; Bonstelle, C.T.; Kaufman, B.; Benson, J.E.; Alfidi, R.J.; Clampitt, M.; Van Dyke, C.; Huss, R.G.

1984-01-01

Magnetic resonance (MR) images of the brainstem region from 100 normal or asymptomatic individuals were reviewed in addition to those of 17 patients with intra-axial brainstem lesions and 15 patients with extra-axial masses around the brainstem. MR was able to demonstrate consistently the normal anatomy of the brainstem and adjacent cisterns, though the distinction between gray and white matter was seldom possible with the present technology. Masses in and around the brainstem were all accurately identified on MR and its sensitivity was superior to that of x-ray computed tomography (CT). These study results show that despite its technical limitations, MR is presently the examination of choice for the evaluation of brainstem abnormalities and eventually it will undoubtedly replace metrizamide CT cisternography
Gamma Knife Treatment of Brainstem Metastases

Science.gov (United States)

Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; MacKay, Alexander R.; Lamoreaux, Wayne T.; Call, Jason A.; Carlson, Jonathan D.; Ling, Benjamin C.; Demakas, John J.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

2014-01-01

The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control. PMID:24886816
Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate.

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Lelkes, Zoltán; Abdurakhmanova, Shamsiiat; Porkka-Heiskanen, Tarja

2017-09-18

The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N-methyl-D-aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G-saporin. In eight Han-Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG-saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep-wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non-REM and REM sleep were decreased significantly during the 3-h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake-enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate. © 2017 European Sleep Research Society.
Brainstem tolerance to conformal radiotherapy of skull base tumors

International Nuclear Information System (INIS)

Debus, J.; Hug, E.B.; Liebsch, N.J.; O'Farrel, D.; Finkelstein, D.; Efird, J.; Munzenrider, J.E.

1997-01-01

Purpose: The aim of this study was to analyze the long-term incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. Methods and Materials: Between 1974 and 1995, 367 patients with chordomas (n = 195) and chondrosarcomas (n = 172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. Following 3D treatment planning with delineation of target volumes and critical nontarget structures dose distributions and dose-volume histograms were calculated. Radiotherapy was given an 1.8 Gy or CGE (=Cobalt Gray Equivalent) dose per fraction, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to ≤64 CGE and to the brainstem center to ≤53 CGE. Results: Follow-up time ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem toxicity was observed in 17 of 367 patients attributable to treatment, resulting in death of three patients. Actuarial rates of 5 and 10-year high-grade toxicity-free survival were 94 and 88%, respectively. Increased risk of brainstem toxicity was significantly associated with maximum dose to brainstem, volume of brainstem receiving ≥50 CGE, ≥55 CGE, and ≥60 CGE, number of surgical procedures, and prevalence of diabetes or high blood pressure. Multivariate analysis identified three independent factors as important prognosticators: number of surgical procedures (p < 0.001), volume of the brainstem receiving 60 CGE (p < 0.001), and prevalence of diabetes (p < 0.01). Conclusions: Tolerance of brainstem to fractionated radiotherapy appears to be a steep function of tissue volume included in high dose regions rather than the maximum dose of brainstem alone. In addition, presence of predisposing factors as well as extent of surgical manipulation can significantly lower brainstem tolerance in the individual patient

Effects of myelin or cell body brainstem lesions on 3-channel Lissajous' trajectories of feline auditory brainstem evoked potentials

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Pratt, H; Zaaroor, M; Bleich, N; Starr, A

1991-01-01

Auditory brainstem evoked potentials (ABEP) were recorded from 16 awake cats to obtain 3-Channel Lissajous' Trajectories (3CLTs) using three orthogonal differential electrode configurations (nasion - midline nuchal ridge, left - right mastoids, vertex - midline under the mandible). Potentials, evoked by monaural 80 dBnHL (re. human threshold) clicks, were studied before, and up to 7 weeks after inducing neuronal lesions localized to the cochlear nucleus (CN) or the superior olivary complex (S...
Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

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Aleman, M; Williams, D C; Guedes, A; Madigan, J E

2015-01-01

An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. Fifteen horses requiring euthanasia. Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Brainstem Auditory Evoked Potential in HIV-Positive Adults.

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Matas, Carla Gentile; Samelli, Alessandra Giannella; Angrisani, Rosanna Giaffredo; Magliaro, Fernanda Cristina Leite; Segurado, Aluísio C

2015-10-20

To characterize the findings of brainstem auditory evoked potential in HIV-positive individuals exposed and not exposed to antiretroviral treatment. This research was a cross-sectional, observational, and descriptive study. Forty-five HIV-positive individuals (18 not exposed and 27 exposed to the antiretroviral treatment - research groups I and II, respectively - and 30 control group individuals) were assessed through brainstem auditory evoked potential. There were no significant between-group differences regarding wave latencies. A higher percentage of altered brainstem auditory evoked potential was observed in the HIV-positive groups when compared to the control group. The most common alteration was in the low brainstem. HIV-positive individuals have a higher percentage of altered brainstem auditory evoked potential that suggests central auditory pathway impairment when compared to HIV-negative individuals. There was no significant difference between individuals exposed and not exposed to antiretroviral treatment.
Midbrain and forebrain patterning delivers immunocytochemically and functionally similar populations of neuropeptide Y containing GABAergic neurons.

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Khaira, S K; Nefzger, C M; Beh, S J; Pouton, C W; Haynes, J M

2011-09-01

Neurons differentiated in vitro from embryonic stem cells (ESCs) have the potential to serve both as models of disease states and in drug discovery programs. In this study, we use sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF-8) to enrich for forebrain and midbrain phenotypes from mouse ESCs. We then investigate, using Ca(2+) imaging and [(3)H]-GABA release studies, whether the GABAergic neurons produced exhibit distinct functional phenotypes. At day 24 of differentiation, reverse transcriptase-PCR showed the presence of both forebrain (Bf-1, Hesx1, Pgc-1α, Six3) and midbrain (GATA2, GATA3) selective mRNA markers in developing forebrain-enriched cultures. All markers were present in midbrain cultures except for Bf-1 and Pgc-1α. Irrespective of culture conditions all GABA immunoreactive neurons were also immunoreactive to neuropeptide Y (NPY) antibodies. Forebrain and midbrain GABAergic neurons responded to ATP (1 mM), L-glutamate (30 μM), noradrenaline (30 μM), acetylcholine (30 μM) and dopamine (30 μM), with similar elevations of intracellular Ca(2+)([Ca(2+)](i)). The presence of GABA(A) and GABA(B) antagonists, bicuculline (30 μM) and CGP55845 (1 μM), increased the elevation of [Ca(2+)](i) in response to dopamine (30 μM) in midbrain, but not forebrain GABAergic neurons. All agonists, except dopamine, elicited similar [(3)H]-GABA release from forebrain and midbrain cultures. Dopamine (30 μM) did not stimulate significant [(3)H]-GABA release in midbrain cultures, although it was effective in forebrain cultures. This study shows that differentiating neurons toward a midbrain fate restricts the expression of forebrain markers. Forebrain differentiation results in the expression of forebrain and midbrain markers. All GABA(+) neurons contain NPY, and show similar agonist-induced elevations of [Ca(2+)](i) and [(3)H]-GABA release. This study indicates that the pharmacological phenotype of these particular neurons may be independent of the addition of
Somatotopic arrangement and location of the corticospinal tract in the brainstem of the human brain.

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Jang, Sung Ho

2011-07-01

The corticospinal tract (CST) is the most important motor pathway in the human brain. Detailed knowledge of CST somatotopy is important in terms of rehabilitative management and invasive procedures for patients with brain injuries. In this study, I conducted a review of nine previous studies of the somatotopical location and arrangement at the brainstem in the human brain. The results of this review indicated that the hand and leg somatotopies of the CST are arranged medio-laterally in the mid to lateral portion of the cerebral peduncle, ventromedial-dorsolaterally in the pontine basis, and medio-laterally in the medullary pyramid. However, few diffusion tensor imaging (DTI) studies have been conducted on this topic, and only nine have been reported: midbrain (2 studies), pons (4 studies), and medulla (1 study). Therefore, further DTI studies should be conducted in order to expand the literature on this topic. In particular, research on midbrain and medulla should be encouraged.
Impairments in musical abilities reflected in the auditory brainstem: evidence from congenital amusia.

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Lehmann, Alexandre; Skoe, Erika; Moreau, Patricia; Peretz, Isabelle; Kraus, Nina

2015-07-01

Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine-grained automatic processing of sounds is impoverished in amusia. Compared with matched non-musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
The anatomy of the human medial forebrain bundle: Ventral tegmental area connections to reward-associated subcortical and frontal lobe regions

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Volker Arnd Coenen

Full Text Available Introduction: Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human medial forebrain bundle (MFB and the connectivity of the ventral tegmental area (VTA. A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the superolateral branch of the MFB (slMFB - is however mandatory to enable an interpretation of distinct therapeutic effects from different interventional treatment modalities in neuropsychiatric disorders (DBS, TMS etc.. This work aims at a normative description of the human MFB (and more detailed the slMFB anatomy with respect to distant prefrontal connections and microstructural features. Methods and material: Healthy subjects (n = 55; mean age ± SD, 40 ± 10 years; 32 females underwent high resolution anatomical magnetic resonance imaging including diffusion tensor imaging. Connectivity of the VTA and the resulting slMFB were investigated on the group level using a global tractography approach. The Desikan/Killiany parceling (8 segments of the prefrontal cortex was used to describe sub-segments of the MFB. A qualitative overlap with Brodmann areas was additionally described. Additionally, a pure visual analysis was performed comparing local and global tracking approaches for their ability to fully visualize the slMFB. Results: The MFB could be robustly described both in the present sample as well as in additional control analyses in data from the human connectome project. Most VTA- connections reached the superior frontal gyrus, the middel frontal gyrus and the lateral orbitofrontal region corresponding to Brodmann areas 10, 9, 8, 11, and 11m. The projections to these regions comprised 97% (right and 98% (left of the total relative fiber counts of the slMFB. Discussion: The anatomical description of the human MFB shows far reaching connectivity of VTA to reward-related subcortical and
Clinical Approach to Supranuclear Brainstem Saccadic Gaze Palsies

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Alexandra Lloyd-Smith Sequeira

2017-08-01

Full Text Available Failure of brainstem supranuclear centers for saccadic eye movements results in the clinical presence of a brainstem-mediated supranuclear saccadic gaze palsy (SGP, which is manifested as slowing of saccades with or without range of motion limitation of eye movements and as loss of quick phases of optokinetic nystagmus. Limitation in the range of motion of eye movements is typically worse with saccades than with smooth pursuit and is overcome with vestibular–ocular reflexive eye movements. The differential diagnosis of SGPs is broad, although acute-onset SGP is most often from brainstem infarction and chronic vertical SGP is most commonly caused by the neurodegenerative condition progressive supranuclear palsy. In this review, we discuss the brainstem anatomy and physiology of the brainstem saccade-generating network; we discuss the clinical features of SGPs, with an emphasis on insights from quantitative ocular motor recordings; and we consider the broad differential diagnosis of SGPs.
Immunohistochemical Mapping of TRK-Fused Gene Products in the Rat Brainstem

International Nuclear Information System (INIS)

Takeuchi, Shigeko; Masuda, Chiaki; Maebayashi, Hisae; Tooyama, Ikuo

2012-01-01

The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It was since reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. As shown in the accompanying paper, we produced an antibody to rat TFG and used it to localize TFG to selected neurons in specific regions. In the present study, we mapped the TFG-positive neurons in the brainstem, cerebellum, and spinal cord of rats. In the brainstem, neurons intensely positive for TFG were distributed in the raphe nuclei, the gigantocellular reticular nucleus, the reticulotegmental nucleus of the pons, and some cranial nerve nuclei such as the trigeminal nuclei, the vestibulocochlear nuclei, and the dorsal motor nucleus of the vagus. Purkinje cells in the cerebellum and motor neurons in the spinal anterior horn were also positive for TFG. These results provide fundamental data for studying the functions of TFG in the brain
Brainstem tolerance to conformal radiotherapy of skull base tumors

International Nuclear Information System (INIS)

Debus, J.; Hug, E.B.; Munzenrider, J.E.; Liebsch, N.J.; O'Farrell, D.; Efird, J.; Daly, W.; Suit, H.D.

1996-01-01

Purpose/Objective: Brainstem tolerance to inhomogenous radiation doses applied by modern conformal radiotherapy has not yet been examined. The aim of this study was to analyse the incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. Materials and Methods: Between 1974 and 1995, 367 patients with chordomas (n=195) and chondrosarcomas (n=172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. All patients had previously undergone biopsy, subtotal or total tumor removal. 104 patients had two or more surgical procedures before radiotherapy. Following 3D treatment planning with delineation of target volumes and critical non-target structures, dose distributions and dose volume histograms were calculated [at the time of treatment delivery]. Radiotherapy was given once a day, 1.8 Gy or CGE (Cobalt Gy Equivalent: Proton Gy X 1.1) per fraction, 5 fractions per week, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to ≤64 CGE and to the brainstem center to ≤53 CGE. Dose distributions were developed to limit dose to brainstem surface and center; current plans limit dose to surface and center to ≤64 CGE and ≤53 CGE, respectively. Brainstem toxicity was scored according to the RTOG grading system. Results: Follow-up ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem symptoms, attributable to the treatment, developed in 17 of 282 patients with local tumor control (6.0%), resulting in death of three patients. The mean time to onset of symptoms was 17 months (range: 4.5 to 177 months). These symptoms appeared in 89.5% within 3 years. Grading of the brainstem toxicity is listed in table 1. Actuarial rates of 5 and 10 year toxicity free survival were 87% and 82% respectively. Increased risk of brainstem toxicity was significantly associated with maximum brainstem dose
Transcriptional maturation of the mouse auditory forebrain.

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Hackett, Troy A; Guo, Yan; Clause, Amanda; Hackett, Nicholas J; Garbett, Krassimira; Zhang, Pan; Polley, Daniel B; Mirnics, Karoly

2015-08-14

The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next-generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (~P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. The main findings were: (1) Global gene expression
A forebrain atlas of the lizard Gekko gecko.

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Smeets, W J; Hoogland, P V; Lohman, A H

1986-12-01

An atlas of the forebrain of the lizard Gekko gecko has been provided, which will serve as the basis for subsequent experimental tracing and immunohistochemical studies. Apart from a strongly developed medial cortex and septal area, the Tokay gecko shows all the main features of the forebrain of the lacertid-type lizards. When its convenience as an experimental animal is also taken into account, this species seems to be very suitable for studying the limbic system in reptiles. The atlas comprises topographical reconstructions of the telencephalon and diencephalon and a series of transverse sections of which the levels have been indicated in the reconstructions. The results obtained in the Gekko are briefly compared with those found in other lizards studied.
Craniofacial Pain: Brainstem Mechanisms

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Barry J Sessle

1996-01-01

Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of
Adult forebrain NMDA receptors gate social motivation and social memory.

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Jacobs, Stephanie; Tsien, Joe Z

2017-02-01

Motivation to engage in social interaction is critical to ensure normal social behaviors, whereas dysregulation in social motivation can contribute to psychiatric diseases such as schizophrenia, autism, social anxiety disorders and post-traumatic stress disorder (PTSD). While dopamine is well known to regulate motivation, its downstream targets are poorly understood. Given the fact that the dopamine 1 (D1) receptors are often physically coupled with the NMDA receptors, we hypothesize that the NMDA receptor activity in the adult forebrain principal neurons are crucial not only for learning and memory, but also for the proper gating of social motivation. Here, we tested this hypothesis by examining sociability and social memory in inducible forebrain-specific NR1 knockout mice. These mice are ideal for exploring the role of the NR1 subunit in social behavior because the NR1 subunit can be selectively knocked out after the critical developmental period, in which NR1 is required for normal development. We found that the inducible deletion of the NMDA receptors prior to behavioral assays impaired, not only object and social recognition memory tests, but also resulted in profound deficits in social motivation. Mice with ablated NR1 subunits in the forebrain demonstrated significant decreases in sociability compared to their wild type counterparts. These results suggest that in addition to its crucial role in learning and memory, the NMDA receptors in the adult forebrain principal neurons gate social motivation, independent of neuronal development. Copyright © 2016 Elsevier Inc. All rights reserved.
Song exposure regulates known and novel microRNAs in the zebra finch auditory forebrain

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Kim Jong H

2011-05-01

Full Text Available Abstract Background In an important model for neuroscience, songbirds learn to discriminate songs they hear during tape-recorded playbacks, as demonstrated by song-specific habituation of both behavioral and neurogenomic responses in the auditory forebrain. We hypothesized that microRNAs (miRNAs or miRs may participate in the changing pattern of gene expression induced by song exposure. To test this, we used massively parallel Illumina sequencing to analyse small RNAs from auditory forebrain of adult zebra finches exposed to tape-recorded birdsong or silence. Results In the auditory forebrain, we identified 121 known miRNAs conserved in other vertebrates. We also identified 34 novel miRNAs that do not align to human or chicken genomes. Five conserved miRNAs showed significant and consistent changes in copy number after song exposure across three biological replications of the song-silence comparison, with two increasing (tgu-miR-25, tgu-miR-192 and three decreasing (tgu-miR-92, tgu-miR-124, tgu-miR-129-5p. We also detected a locus on the Z sex chromosome that produces three different novel miRNAs, with supporting evidence from Northern blot and TaqMan qPCR assays for differential expression in males and females and in response to song playbacks. One of these, tgu-miR-2954-3p, is predicted (by TargetScan to regulate eight song-responsive mRNAs that all have functions in cellular proliferation and neuronal differentiation. Conclusions The experience of hearing another bird singing alters the profile of miRNAs in the auditory forebrain of zebra finches. The response involves both known conserved miRNAs and novel miRNAs described so far only in the zebra finch, including a novel sex-linked, song-responsive miRNA. These results indicate that miRNAs are likely to contribute to the unique behavioural biology of learned song communication in songbirds.
Effects of heavy ions on rabbit tissues: damage to the forebrain

International Nuclear Information System (INIS)

Cox, A.B.; Keng, P.C.; Lee, A.C.; Lett, J.T.

1982-01-01

As part of a study of progressive radiation effects in normal tissues, the forebrains of New Zealand white rabbits (Oryctolagus cuniculus) (about 6 weeks old) were irradiated locally with single acute doses of 60 Co γ-photons (LETsub(infinity)=0.3 keV/μm), Ne ions (LETsub(infinity)=35+-3 keV/μm) or Ar ions (LETsub(infinity)=90+-5 keV/μm). Other rabbits received fractionated doses of 60 Co γ-photons according to a standard radiotherapeutic protocol. Irradiated rabbits and appropriately aged controls were sacrificed at selected intervals, and whole sagittal sections of their brains were examined for pathological changes. Forebrain damage was scored with subjective indices based on histological differences between the anterior (irradiated) and posterior (unirradiated) regions of the brain. Those indices ranged from zero (no apparent damage) to five (severe infarctions, etc.). At intermediate levels of forebrain damage, the relative biological effectiveness (r.b.e.) of each heavy ion was similar to that found for alopecia and cataractogenesis, and the early expression of the damage was also accelerated as the LETsub(infinity) increased. Late deterioration of the forebrain appeared also to be accelerated by increasing LETsub(infinity), although its accurate quantification was not possible because other priorities in the overall experimental design limited systematic sacrifice of the animals. (author)
Brainstem tumors: Current management and future directions

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Pablo F Recinos

2012-01-01

Full Text Available Tumors arising in the brainstem comprise 10-20% of all pediatric central nervous system (CNS tumors and account for a small percentage in adults. The prognosis for these tumors was considered uniformly poor prior to the era of modern neuroimaging and the location was fraught with disaster being considered a ′no man′s land′ for neurosurgeons. Following the introduction of advanced imaging modalities and neurophysiological monitoring, striking progress has occurred in the management of these lesions. Brainstem tumors are presently classified based on their anatomic location, focality, and histopathology. This article reviews the current classification of brainstem tumors, current management options, and future directions in the treatment for these rare tumors.
Pediatric brainstem oligodendroglioma

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Sandeep Mohindra

2012-01-01

Full Text Available The authors present the first report of pediatric brainstem oligodendroglioma, infiltrating midbrain, and medulla oblongata. The report details clinical features, radiological findings, and surgical steps. As this entity is exceedingly uncommon, the overall epidemiology, prognosis, and long-term outcome remain far from established.
Ascending connections to the forebrain in the Tegu lizard.

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Lohman, A H; van Woerden-Verkley, I

1978-12-01

The ascending connections to the striatum and the cortex of the Tegu lizard, Tupinambis nigropunctatus, were studied by means of anterograde fiber degeneration and retrograde axonal transport. The striatum receives projections by way of the dorsal peduncle of the lateral forebrain bundle from four dorsal thalamic nuclei: nucleus rotundus, nucleus reuniens, the posterior part of the dorsal lateral geniculate nucleus and nucleus dorsomedialis. The former three nuclei project to circumscribed areas of the dorsal striatum, whereas nucleus dorsomedialis has a distribution to the whole dorsal striatum. Other sources of origin to the striatum are the mesencephalic reticular formation, substantia nigra and nucleus cerebelli lateralis. With the exception of the latter afferentation all these projections are ipsilateral. The ascending connections to the pallium originate for the major part from nucleus dorsolateralis anterior of the dorsal thalamus. The fibers course in both the medial forebrain bundle and the dorsal peduncle of the lateral forebrain bundle and terminate ipsilaterally in the middle of the molecular layer of the small-celled part of the mediodorsal cortex and bilaterally above the intermediate region of the dorsal cortex. The latter area is reached also by fibers from the septal area. The large-celled part of the mediodorsal cortex receives projections from nucleus raphes superior and the corpus mammillare.
Cellular localization of transforming growth factor-alpha mRNA in rat forebrain.

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Seroogy, K B; Lundgren, K H; Lee, D C; Guthrie, K M; Gall, C M

1993-05-01

The cellular localization of transforming growth factor-alpha (TGF alpha) mRNA in juvenile and adult rat forebrain was examined using in situ hybridization with a 35S-labeled cRNA probe. TGF alpha cRNA-labeled neuronal perikarya were distributed across many forebrain regions including the olfactory bulb, caudate-putamen, nucleus accumbens, olfactory tubercle, ventral pallidum, amygdala, hippocampal stratum granulosum and CA3 stratum pyramidale, and piriform, entorhinal, and retrosplenial cortices. TGF alpha cRNA-hybridizing cells were also localized to several thalamic nuclei and to the suprachiasmatic, dorsomedial, and ventromedial nuclei of the hypothalamus. In addition, labeled cells were present in regions of white matter including the corpus callosum, anterior commissure, internal and external capsules, optic tract, and lateral olfactory tract. Thus, both neurons and glia appear to synthesize TGF alpha in normal brain. Hybridization densities were greater in neuronal fields at 2 weeks of age compared with the adult, suggesting a role for TGF alpha in the development of several forebrain systems. Our results demonstrating the prominent and wide-spread expression of TGF alpha mRNA in forebrain, combined with the extremely low abundance of epidermal growth factor mRNA in brain, support the argument that TGF alpha is the principal endogenous ligand for the epidermal growth factor receptor in normal brain.

Medial forebrain bundle lesions fail to structurally and functionally disconnect the ventral tegmental area from many ipsilateral forebrain nuclei: implications for the neural substrate of brain stimulation reward.

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Simmons, J M; Ackermann, R F; Gallistel, C R

1998-10-15

Lesions in the medial forebrain bundle rostral to a stimulating electrode have variable effects on the rewarding efficacy of self-stimulation. We attempted to account for this variability by measuring the anatomical and functional effects of electrolytic lesions at the level of the lateral hypothalamus (LH) and by correlating these effects to postlesion changes in threshold pulse frequency (pps) for self-stimulation in the ventral tegmental area (VTA). We implanted True Blue in the VTA and compared cell labeling patterns in forebrain regions of intact and lesioned animals. We also compared stimulation-induced regional [14C]deoxyglucose (DG) accumulation patterns in the forebrains of intact and lesioned animals. As expected, postlesion threshold shifts varied: threshold pps remained the same or decreased in eight animals, increased by small but significant amounts in three rats, and increased substantially in six subjects. Unexpectedly, LH lesions did not anatomically or functionally disconnect all forebrain nuclei from the VTA. Most septal and preoptic regions contained equivalent levels of True Blue label in intact and lesioned animals. In both intact and lesioned groups, VTA stimulation increased metabolic activity in the fundus of the striatum (FS), the nucleus of the diagonal band, and the medial preoptic area. On the other hand, True Blue labeling demonstrated anatomical disconnection of the accumbens, FS, substantia innominata/magnocellular preoptic nucleus (SI/MA), and bed nucleus of the stria terminalis. [14C]DG autoradiography indicated functional disconnection of the lateral preoptic area and SI/MA. Correlations between patterns of True Blue labeling or [14C]deoxyglucose accumulation and postlesion shifts in threshold pulse frequency were weak and generally negative. These direct measures of connectivity concord with the behavioral measures in suggesting a diffuse net-like connection between forebrain nuclei and the VTA.
Speech-evoked brainstem frequency-following responses during verbal transformations due to word repetition.

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Galbraith, G C; Jhaveri, S P; Kuo, J

1997-01-01

Speech-evoked brainstem frequency-following responses (FFRs) were recorded to repeated presentations of the same stimulus word. Word repetition results in illusory verbal transformations (VTs) in which word perceptions can differ markedly from the actual stimulus. Previous behavioral studies support an explanation of VTs based on changes in arousal or attention. Horizontal and vertical dipole FFRs were recorded to assess responses with putative origins in the auditory nerve and central brainstem, respectively. FFRs were recorded from 18 subjects when they correctly heard the stimulus and when they reported VTs. Although horizontal and vertical dipole FFRs showed different frequency response patterns, dipoles did not differentiate between perceptual conditions. However, when subjects were divided into low- and high-VT groups (based on percentage of VT trials), a significant Condition x Group interaction resulted. This interaction showed the largest difference in FFR amplitudes during VT trials, with the low-VT group showing increased amplitudes, and the high-VT group showing decreased amplitudes, relative to trials in which the stimulus was correctly perceived. These results demonstrate measurable subject differences in the early processing of complex signals, due to possible effects of attention on the brainstem FFR. The present research shows that the FFR is useful in understanding human language as it is coded and processed in the brainstem auditory pathway.
Detection of brainstem involvemetn in multiple sclerosis

International Nuclear Information System (INIS)

Martinelli, V.; Comi, G.; Filippi, M.; Sora, M.G.N.; Magnani, G.; Locatelli, T.; Visciani, A.; Scotti, G.; Canal, N.

1989-01-01

The Gradient Refocusing Technique, which seppresses the influence of cerebrospinal fluis (GSF) and vascular motion artifact on MRI sensitivity, is applied combined with Brainstem Auditory Evoked Potentials (BAEPs) and median Somatosensory Evoked Potentials (SEPs) in the evaluation of the brainstem in 30 MS patients with clinical signs of involvement of this structure in order to reevaluate the sensitivity of these techniques. (Author). 2 refs.; 1 tab
Magnetic resonance imaging in brain-stem tumors

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Nomura, Mikio; Saito, Hisazumi; Akino, Minoru; Abe, Hiroshi.

1988-01-01

Four patients with brain-stem tumors underwent magnetic resonance imaging (MRI) before and after radiotherapy. The brain-stem tumors were seen as a low signal intensity on T1-weighted images and as a high signal intensity on T2-weighted images. A tumor and its anatomic involvement were more clearly visualized on MRI than on cuncurrently performed CT. Changes in tumor before and after radiotherapy could be determined by measuring the diameter of tumor on sagittal and coronal images. This allowed quantitative evaluation of the reduction of tumor in association with improvement of symptoms. The mean T1 value in the central part of tumors was shortened in all patients after radiotherapy. The results indicate that MRI may assist in determining the effect of radiotherapy for brain-stem tumors. (Namekawa, K)
Brainstem disconnection

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Duffield, Curtis; Wootton-Gorges, Sandra L.; Jocson, Jennifer

2009-01-01

Brainstem disconnection is a very rare neonatal abnormality, with only seven cases reported. We report a unique case of a neonate who presented at delivery with hypertonia, dysmorphic facial features, and respiratory distress, as well as numerous musculoskeletal and genitourinary abnormalities. MRI of the brain showed disconnection between the pons and medulla with cerebellar hypoplasia and absent cerebellar peduncles. It aided in the description of the neurological and vascular anomalies associated with this diagnosis. (orig.)
Brainstem disconnection

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Duffield, Curtis; Wootton-Gorges, Sandra L. [University of California Davis, Medical Center and UC Davis Children' s Hospital, Department of Radiology, Sacramento, CA (United States); Jocson, Jennifer [University of California Davis, Medical Center and UC Davis Children' s Hospital, Department of Pediatrics, Sacramento, CA (United States)

2009-12-15

Brainstem disconnection is a very rare neonatal abnormality, with only seven cases reported. We report a unique case of a neonate who presented at delivery with hypertonia, dysmorphic facial features, and respiratory distress, as well as numerous musculoskeletal and genitourinary abnormalities. MRI of the brain showed disconnection between the pons and medulla with cerebellar hypoplasia and absent cerebellar peduncles. It aided in the description of the neurological and vascular anomalies associated with this diagnosis. (orig.)
Mast cells in the sheep, hedgehog and rat forebrain

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MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

1999-01-01

The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696
Lyme disease of the brainstem

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Kalina, Peter [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Decker, Andrew [Northern Westchester Hospital Center, Department of Neurology, Mt. Kisco, NY (United States); Kornel, Ezriel [Northern Westchester Hospital Center, Division of Neurosurgery, Mt. Kisco, NY (United States); Halperin, John J. [North Shore University Hospital, Department of Neurology, Manhasset, NY (United States)

2005-12-01

Lyme disease is a multisystem infectious disease caused by the tick-borne spirochete, Borrelia burgdorferi. Central nervous system (CNS) involvement typically causes local inflammation, most commonly meningitis, but rarely parenchymal brain involvement. We describe a patient who presented with clinical findings suggesting a brainstem process. Magnetic resonance imaging (MRI) and positron emission tomography (PET) suggested a brainstem neoplasm. Prior to biopsy, laboratory evaluation led to the diagnosis of Lyme disease. Clinical and imaging abnormalities improved markedly following antimicrobial therapy. We describe Lyme disease involvement of the cerebellar peduncles with hypermetabolism on PET. Although MRI is the primary imaging modality for most suspected CNS pathology, the practical applications of PET continue to expand. (orig.)
Lyme disease of the brainstem

International Nuclear Information System (INIS)

Kalina, Peter; Decker, Andrew; Kornel, Ezriel; Halperin, John J.

2005-01-01

Lyme disease is a multisystem infectious disease caused by the tick-borne spirochete, Borrelia burgdorferi. Central nervous system (CNS) involvement typically causes local inflammation, most commonly meningitis, but rarely parenchymal brain involvement. We describe a patient who presented with clinical findings suggesting a brainstem process. Magnetic resonance imaging (MRI) and positron emission tomography (PET) suggested a brainstem neoplasm. Prior to biopsy, laboratory evaluation led to the diagnosis of Lyme disease. Clinical and imaging abnormalities improved markedly following antimicrobial therapy. We describe Lyme disease involvement of the cerebellar peduncles with hypermetabolism on PET. Although MRI is the primary imaging modality for most suspected CNS pathology, the practical applications of PET continue to expand. (orig.)
Systematic Morphometry of Catecholamine Nuclei in the Brainstem.

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Bucci, Domenico; Busceti, Carla L; Calierno, Maria T; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

2017-01-01

Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology.
Systematic Morphometry of Catecholamine Nuclei in the Brainstem

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Domenico Bucci

2017-11-01

Full Text Available Catecholamine nuclei within the brainstem reticular formation (RF play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH immune-positive cells of the brainstem correspond to dopamine (DA-, norepinephrine (NE-, and epinephrine (E-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology.
Tractography of the brainstem in major depressive disorder using diffusion tensor imaging.

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Yun Ju C Song

Full Text Available BACKGROUND: The brainstem is the main region that innervates neurotransmitter release to the Hypothalamic-Pituitary Adrenal (HPA axis and fronto-limbic circuits, two key brain circuits found to be dysfunctional in Major Depressive Disorder (MDD. However, the brainstem's role in MDD has only been evaluated in limited reports. Using Diffusion Tensor Imaging (DTI, we investigated whether major brainstem white matter tracts that relate to these two circuits differ in MDD patients compared to healthy controls. METHODS: MDD patients (n = 95 and age- and gender-matched controls (n = 34 were assessed using probabilistic tractography of DTI to delineate three distinct brainstem tracts: the nigrostriatal tract (connecting brainstem to striatum, solitary tract (connecting brainstem to amygdala and corticospinal tract (connecting brainstem to precentral cortex. Fractional anisotropy (FA was used to measure the white matter integrity of these tracts, and measures were compared between MDD and control participants. RESULTS: MDD participants were characterized by a significant and specific decrease in white matter integrity of the right solitary tract (p<0.009 using independent t-test, which is a "bottom up" afferent pathway that connects the brainstem to the amygdala. This decrease was not related to symptom severity. CONCLUSIONS: The results provide new evidence to suggest that structural connectivity between the brainstem and the amygdala is altered in MDD. These results are interesting in light of predominant theories regarding amygdala-mediated emotional reactivity observed in functional imaging studies of MDD. The characterization of altered white matter integrity in the solitary tract in MDD supports the possibility of dysfunctional brainstem-amygdala connectivity impacting vulnerable circuits in MDD.
Receptors for GRP/bombesin-like peptides in the rat forebrain

International Nuclear Information System (INIS)

Wolf, S.S.; Moody, T.W.

1985-01-01

Binding sites in the rat forebrain were characterized using ( 125 I-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides
Mechanical Characterization of Immature Porcine Brainstem in Tension at Dynamic Strain Rates.

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Zhao, Hui; Yin, Zhiyong; Li, Kui; Liao, Zhikang; Xiang, Hongyi; Zhu, Feng

2016-01-21

Many brain injury cases involve pediatric road traffic accidents, and among these, brainstem injury causes disastrous outcomes. A thorough understanding of the tensile characterization of immature brainstem tissue is crucial in modeling traumatic brain injury sustained by children, but limited experimental data in tension is available for the immature brain tissue at dynamic strain rates. We harvested brainstem tissue from immature pigs (about 4 weeks old, and at a developmental stage similar to that of human toddlers) as a byproduct from a local slaughter house and very carefully prepared the samples. Tensile tests were performed on specimens at dynamic strain rates of 2/s, 20/s, and 100/s using a biological material instrument. The constitutive models, Fung, Ogden, Gent, and exponential function, for immature brainstem tissue material property were developed for the recorded experimental data using OriginPro 8.0 software. The t test was performed for infinitesimal shear modules. The curves of stress-versus-stretch ratio were convex in shape, and inflection points were found in all the test groups at the strain of about 2.5%. The average Lagrange stress of the immature brainstem specimen at the 30% strain at the strain rates of 2, 20, and 100/s was 273±114, 515±107, and 1121±197 Pa, respectively. The adjusted R-Square (R2) of Fung, Ogden, Gent, and exponential model was 0.820≤R2≤0.933, 0.774≤R2≤0.940, 0.650≤R2≤0.922, and 0.852≤R2≤0.981, respectively. The infinitesimal shear modulus of the strain energy functions showed a significant association with the strain rate (pmaterial in dynamic tensile tests, and the tissue becomes stiffer with increased strain rate. The reported results may be useful in the study of brain injuries in children who sustain injuries in road traffic accidents. Further research in more detail should be performed in the future.
Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions.

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Mingote, Susana; Chuhma, Nao; Kusnoor, Sheila V; Field, Bianca; Deutch, Ariel Y; Rayport, Stephen

2015-12-09

In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DAT(IREScre) mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome. Dopamine neurons are important for the control of motivated behavior and are involved in the pathophysiology of several major neuropsychiatric disorders. Recent studies have shown that some ventral midbrain dopamine neurons are
A clinical study of brainstem infarction identified on magnetic resonance imaging

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Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

1993-04-01

We conducted a clinical study of 155 cases that were confirmed to have brainstem infarctions on MRI (T[sub 1]-weighted image showed a low signal and T[sub 2]-weighted image showed a high signal, measuring in excess of 2 x 2 mm). The majority of the brainstem infarction was located in the pontine base in 132 cases (85.2%). Of these, 19 cases had double lesions including infarctions in the pontine base. Second infarctions frequently occurred in the cerebral peduncle or medical medulla oblongata, unilateral to the pontine infarctions. In addition to 98 symptomatic cases, there were 57 cases of 'asymptomatic' brainstem infarction. They comprised 24 cases accompanying other symptomatic cerebrovascular diseases in the supratentorium and 33 cases of transient subjective complaints such as headache or vertigo-dizziness. Complication by supratentorial infarctions was significantly frequent in cases of brainstem infarction (p<0.001), 122 of 155 cases (78.7%), especially in the pontine base (88.6%); while in the control cases (without brainstem infarction) only 65 of 221 cases (29.4%). These findings are considered to show the widespread progress of arteriosclerosis in brainstem infarction, especially in ones in the pontine base. (author).
LANGUAGE EXPERIENCE SHAPES PROCESSING OF PITCH RELEVANT INFORMATION IN THE HUMAN BRAINSTEM AND AUDITORY CORTEX: ELECTROPHYSIOLOGICAL EVIDENCE.

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Krishnan, Ananthanarayan; Gandour, Jackson T

2014-12-01

Pitch is a robust perceptual attribute that plays an important role in speech, language, and music. As such, it provides an analytic window to evaluate how neural activity relevant to pitch undergo transformation from early sensory to later cognitive stages of processing in a well coordinated hierarchical network that is subject to experience-dependent plasticity. We review recent evidence of language experience-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem and auditory cortex. We present evidence that shows enhanced representation of linguistically-relevant pitch dimensions or features at both the brainstem and cortical levels with a stimulus-dependent preferential activation of the right hemisphere in native speakers of a tone language. We argue that neural representation of pitch-relevant information in the brainstem and early sensory level processing in the auditory cortex is shaped by the perceptual salience of domain-specific features. While both stages of processing are shaped by language experience, neural representations are transformed and fundamentally different at each biological level of abstraction. The representation of pitch relevant information in the brainstem is more fine-grained spectrotemporally as it reflects sustained neural phase-locking to pitch relevant periodicities contained in the stimulus. In contrast, the cortical pitch relevant neural activity reflects primarily a series of transient temporal neural events synchronized to certain temporal attributes of the pitch contour. We argue that experience-dependent enhancement of pitch representation for Chinese listeners most likely reflects an interaction between higher-level cognitive processes and early sensory-level processing to improve representations of behaviorally-relevant features that contribute optimally to perception. It is our view that long
TASK Channels on Basal Forebrain Cholinergic Neurons Modulate Electrocortical Signatures of Arousal by Histamine.

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Vu, Michael T; Du, Guizhi; Bayliss, Douglas A; Horner, Richard L

2015-10-07

Basal forebrain cholinergic neurons are the main source of cortical acetylcholine, and their activation by histamine elicits cortical arousal. TWIK-like acid-sensitive K(+) (TASK) channels modulate neuronal excitability and are expressed on basal forebrain cholinergic neurons, but the role of TASK channels in the histamine-basal forebrain cholinergic arousal circuit is unknown. We first expressed TASK channel subunits and histamine Type 1 receptors in HEK cells. Application of histamine in vitro inhibited the acid-sensitive K(+) current, indicating a functionally coupled signaling mechanism. We then studied the role of TASK channels in modulating electrocortical activity in vivo using freely behaving wild-type (n = 12) and ChAT-Cre:TASK(f/f) mice (n = 12), the latter lacking TASK-1/3 channels on cholinergic neurons. TASK channel deletion on cholinergic neurons significantly altered endogenous electroencephalogram oscillations in multiple frequency bands. We then identified the effect of TASK channel deletion during microperfusion of histamine into the basal forebrain. In non-rapid eye movement sleep, TASK channel deletion on cholinergic neurons significantly attenuated the histamine-induced increase in 30-50 Hz activity, consistent with TASK channels contributing to histamine action on basal forebrain cholinergic neurons. In contrast, during active wakefulness, histamine significantly increased 30-50 Hz activity in ChAT-Cre:TASK(f/f) mice but not wild-type mice, showing that the histamine response depended upon the prevailing cortical arousal state. In summary, we identify TASK channel modulation in response to histamine receptor activation in vitro, as well as a role of TASK channels on cholinergic neurons in modulating endogenous oscillations in the electroencephalogram and the electrocortical response to histamine at the basal forebrain in vivo. Attentive states and cognitive function are associated with the generation of γ EEG activity. Basal forebrain
Efficient in vivo electroporation of the postnatal rodent forebrain.

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Camille Boutin

Full Text Available Functional gene analysis in vivo represents still a major challenge in biomedical research. Here we present a new method for the efficient introduction of nucleic acids into the postnatal mouse forebrain. We show that intraventricular injection of DNA followed by electroporation induces strong expression of transgenes in radial glia, neuronal precursors and neurons of the olfactory system. We present two proof-of-principle experiments to validate our approach. First, we show that expression of a human isoform of the neural cell adhesion molecule (hNCAM-140 in radial glia cells induces their differentiation into cells showing a neural precursor phenotype. Second, we demonstrate that p21 acts as a cell cycle inhibitor for postnatal neural stem cells. This approach will represent an important tool for future studies of postnatal neurogenesis and of neural development in general.
Is enhanced MRI helpful in brainstem infarction?

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Jeong, Y. M.; Shin, G. H.; Choi, W. S. [Kyung Hee University Hospital, Seoul (Korea, Republic of)

1994-12-15

To determine the role of MR contrast enhancement in evaluating time course of brainstem infarction. MR imaging with IV administration of gadopentetate dimeglumine was retrospectively reviewed in 43 patients with clinically and radiologically documented brainstem infarctions. The pattern of infarction was classified into spotty and patchy. Presence of parenchymal enhancement in infarction was evaluated. By location, there were 34 pontine, 3 midbrain, 6 medullary infarctions. The age of the infarctions ranged from 1 day to 9 months, with 5 patients scanned within 3 days and 10 scanned within 2 weeks of clinical ictus. Abnormalities on T2-weighted images were encountered in every case, with spotty pattern in 14 cases and patchy pattern in 29 cases. Parenchymal contrast enhancement was seen in 9 cases(20%), primarily occurring between days 8 and 20. MR contrast enhancement in brainstem infarction was infrequent that it may not be useful in the estimation of the age of infarction.

Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

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Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

2017-02-01

It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.
Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

International Nuclear Information System (INIS)

Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S.

2006-01-01

We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)
Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan)

2006-03-15

We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)
Polysialylated-neural cell adhesion molecule (PSA-NCAM in the human trigeminal ganglion and brainstem at prenatal and adult ages

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Melis Tiziana

2008-11-01

Full Text Available Abstract Background The polysialylated neuronal cell adhesion molecule (PSA-NCAM is considered a marker of developing and migrating neurons and of synaptogenesis in the immature vertebrate nervous system. However, it persists in the mature normal brain in some regions which retain a capability for morphofunctional reorganization throughout life. With the aim of providing information relevant to the potential for dynamic changes of specific neuronal populations in man, this study analyses the immunohistochemical occurrence of PSA-NCAM in the human trigeminal ganglion (TG and brainstem neuronal populations at prenatal and adult age. Results Western blot analysis in human and rat hippocampus supports the specificity of the anti-PSA-NCAM antibody and the immunodetectability of the molecule in postmortem tissue. Immunohistochemical staining for PSA-NCAM occurs in TG and several brainstem regions during prenatal life and in adulthood. As a general rule, it appears as a surface staining suggestive of membrane labelling on neuronal perikarya and proximal processes, and as filamentous and dot-like elements in the neuropil. In the TG, PSA-NCAM is localized to neuronal perikarya, nerve fibres, pericellular networks, and satellite and Schwann cells; further, cytoplasmic perikaryal staining and positive pericellular fibre networks are detectable with higher frequency in adult than in newborn tissue. In the adult tissue, positive neurons are mostly small- and medium-sized, and amount to about 6% of the total ganglionic population. In the brainstem, PSA-NCAM is mainly distributed at the level of the medulla oblongata and pons and appears scarce in the mesencephalon. Immunoreactivity also occurs in discretely localized glial structures. At all ages examined, PSA-NCAM occurs in the spinal trigeminal nucleus, solitary nuclear complex, vestibular and cochlear nuclei, reticular formation nuclei, and most of the precerebellar nuclei. In specimens of different age
Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.

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Tan, Soon Hao; Ong, Kien Chai; Wong, Kum Thong

2014-11-01

Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.
Analysis of diffuse brain injury with primary brainstem lesion on MRI

International Nuclear Information System (INIS)

Shibata, Masayoshi; Matsumae, Mitsunori; Shimoda, Masami; Ishizaka, Hideo; Shiramizu, Hideki; Morita, Seiji; Tsugane, Ryuichi

2003-01-01

It has been reported that diffuse brain injury patients with primary brainstem lesions have a poor prognosis. Predicting the existence of brainstem injury at hospital arrival is problematic in actual clinical practice. We conducted magnetic resonance imaging (MRI), to visualize brainstem lesions clearly, and retrospectively analyzed predictive factors of brainstem lesions by stepwise multiple logistic regression analysis of patient characteristics, neurological findings, laboratory data, and CT findings at arrival in each case. We compared 24 patients with brainstem lesion and 60 without using MRI obtained less than 3 weeks after admission. Items investigated were blood pressure immediately after hospital arrival, arterial blood gas analysis, existence of abnormal respiration, blow direction, Glasgow coma scale (GCS), light reflex, oculocephalic reflex, corneal reflex, intracranial pressure, jugular venous oxygen saturation, and CT findings such as existence of subarachnoid hemorrhage at the suprasellar cistern, perimesencephalic cistern and convexity, lesions on the thalamus and basal ganglia, gliding contusion, intraventricular hemorrhage and Traumatic Coma Data Bank classification. Independent predictive factors of primary brainstem lesion included impaired light reflex (odds ratio: 2.269), subarachnoid hemorrhage at convexity (odds ratio: 3.592) and suprasellar cistern (odds ratio: 2.458), and Traumatic Coma Data Bank group III (odds ratio: 11.062). (author)
Clinical and radiological features of hypertensive brainstem encephalopathy

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Xiao-qiu LI

2015-07-01

Full Text Available Objective　To discuss the diagnosis and treatment of hypertensive brainstem encephalopathy. Methods　 The clinical and imaging data of 3 cases of hypertensive brainstem encephalopathy were summarized and analyzed for the purpose of improving the acumen in diagnosis and treatment. Results　All the 3 patients showed relatively mild clinical symptoms, and they were misdiagnosed in different degrees during the treatment, but their clinical symptoms were improved by rapid and effective antihypertensive therapy. Cerebral CT and MRI scans revealed extensive abnormal signals in brain stem, with or without supratentorial lesions and brain stem hemorrhage. The lesions as revealed by imaging were improved significantly after treatment. Conclusions　Clinical-radiographic dissociation is the classic feature of hypertensive brainstem encephalopathy. The clinical symptoms and lesions as shown by imaging could be improved after active treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.03
Prosomeric map of the lamprey forebrain based on calretinin immunocytochemistry, Nissl stain, and ancillary markers.

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Pombal, M A; Puelles, L

1999-11-22

The structural organization of the lamprey extratelencephalic forebrain is re-examined from the perspective of the prosomeric segmental paradigm. The question asked was whether the prosomeric forebrain model used for gnathostomes is of material advantage for interpreting subdivisions in the lamprey forebrain. To this aim, the main longitudinal and transverse landmarks recognized by the prosomeric model in other vertebrates were identified in Nissl-stained lamprey material. Lines of cytoarchitectural discontinuity and contours of migrated neuronal groups were mapped in a two-dimensional sagittal representation and were also classified according to their radial position. Immunocytochemical mapping of calretinin expression in adjacent sections served to define particular structural units better, in particular, the dorsal thalamus. These data were complemented by numerous other chemoarchitectonic observations obtained with ancillary markers, which identified additional specific formations, subdivisions, or boundaries. Emphasis was placed on studying whether such chemically defined neuronal groups showed boundaries aligned with the postulated inter- or intraprosomeric boundaries. The course of diverse axonal tracts was studied also with regard to their prosomeric topography. This analysis showed that the full prosomeric model applies straightforwardly to the lamprey forebrain. This finding implies that a common segmental and longitudinal organization of the neural tube may be primitive for all vertebrates. Interesting novel aspects appear in the interpretation of the lamprey pretectum, the dorsal and ventral thalami, and the hypothalamus. The topologic continuity of the prosomeric forebrain regions with evaginated or non-evaginated portions of the telencephalon was also examined. Copyright 1999 Wiley-Liss, Inc.
NCAM deficiency in the mouse forebrain impairs innate and learned avoidance behaviours.

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Brandewiede, J; Stork, O; Schachner, M

2014-06-01

The neural cell adhesion molecule (NCAM) has been implicated in the development and plasticity of neural circuits and the control of hippocampus- and amygdala-dependent learning and behaviour. Previous studies in constitutive NCAM null mutants identified emotional behaviour deficits related to disturbances of hippocampal and amygdala functions. Here, we studied these behaviours in mice conditionally deficient in NCAM in the postmigratory forebrain neurons. We report deficits in both innate and learned avoidance behaviours, as observed in elevated plus maze and passive avoidance tasks. In contrast, general locomotor activity, trait anxiety or neophobia were unaffected by the mutation. Altered avoidance behaviour of the conditional NCAM mutants was associated with a deficit in serotonergic signalling, as indicated by their reduced responsiveness to (±)-8-hydroxy-2-(dipropylamino)-tetralin-induced hypothermia. Another serotonin-dependent behaviour, namely intermale aggression that is massively increased in constitutively NCAM-deficient mice, was not affected in the forebrain-specific mutants. Our data suggest that genetically or environmentally induced changes of NCAM expression in the late postnatal and mature forebrain determine avoidance behaviour and serotonin (5-HT)1A receptor signalling. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits.

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Snider, Kaitlin H; Dziema, Heather; Aten, Sydney; Loeser, Jacob; Norona, Frances E; Hoyt, Kari; Obrietan, Karl

2016-07-15

A large body of literature has shown that the disruption of circadian clock timing has profound effects on mood, memory and complex thinking. Central to this time keeping process is the master circadian pacemaker located within the suprachiasmatic nucleus (SCN). Of note, within the central nervous system, clock timing is not exclusive to the SCN, but rather, ancillary oscillatory capacity has been detected in a wide range of cell types and brain regions, including forebrain circuits that underlie complex cognitive processes. These observations raise questions about the hierarchical and functional relationship between the SCN and forebrain oscillators, and, relatedly, about the underlying clock-gated synaptic circuitry that modulates cognition. Here, we utilized a clock knockout strategy in which the essential circadian timing gene Bmal1 was selectively deleted from excitatory forebrain neurons, whilst the SCN clock remained intact, to test the role of forebrain clock timing in learning, memory, anxiety, and behavioral despair. With this model system, we observed numerous effects on hippocampus-dependent measures of cognition. Mice lacking forebrain Bmal1 exhibited deficits in both acquisition and recall on the Barnes maze. Notably, loss of forebrain Bmal1 abrogated time-of-day dependent novel object location memory. However, the loss of Bmal1 did not alter performance on the elevated plus maze, open field assay, and tail suspension test, indicating that this phenotype specifically impairs cognition but not affect. Together, these data suggest that forebrain clock timing plays a critical role in shaping the efficiency of learning and memory retrieval over the circadian day. Copyright © 2016 Elsevier B.V. All rights reserved.
Decreased levels of free D-aspartic acid in the forebrain of serine racemase (Srr) knock-out mice.

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Horio, Mao; Ishima, Tamaki; Fujita, Yuko; Inoue, Ran; Mori, Hisashi; Hashimoto, Kenji

2013-05-01

d-Serine, an endogenous co-agonist of the N-methyl-d-aspartate (NMDA) receptor is synthesized from l-serine by serine racemase (SRR). A previous study of Srr knockout (Srr-KO) mice showed that levels of d-serine in forebrain regions, such as frontal cortex, hippocampus, and striatum, but not cerebellum, of mutant mice are significantly lower than those of wild-type (WT) mice, suggesting that SRR is responsible for d-serine production in the forebrain. In this study, we attempted to determine whether SRR affects the level of other amino acids in brain tissue. We found that tissue levels of d-aspartic acid in the forebrains (frontal cortex, hippocampus and striatum) of Srr-KO mice were significantly lower than in WT mice, whereas levels of d-aspartic acid in the cerebellum were not altered. Levels of d-alanine, l-alanine, l-aspartic acid, taurine, asparagine, arginine, threonine, γ-amino butyric acid (GABA) and methionine, remained the same in frontal cortex, hippocampus, striatum and cerebellum of WT and mutant mice. Furthermore, no differences in d-aspartate oxidase (DDO) activity were detected in the forebrains of WT and Srr-KO mice. These results suggest that SRR and/or d-serine may be involved in the production of d-aspartic acid in mouse forebrains, although further detailed studies will be necessary to confirm this finding. Copyright © 2013 Elsevier Ltd. All rights reserved.
Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.

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Galbraith, G C

2001-06-01

The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.
Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain.

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Choe, Katrina Y; Sanchez, Carlos F; Harris, Neil G; Otis, Thomas S; Mathews, Paul J

2018-06-01

Complex animal behavior is produced by dynamic interactions between discrete regions of the brain. As such, defining functional connections between brain regions is critical in gaining a full understanding of how the brain generates behavior. Evidence suggests that discrete regions of the cerebellar cortex functionally project to the forebrain, mediating long-range communication potentially important in motor and non-motor behaviors. However, the connectivity map remains largely incomplete owing to the challenge of driving both reliable and selective output from the cerebellar cortex, as well as the need for methods to detect region specific activation across the entire forebrain. Here we utilize a paired optogenetic and fMRI (ofMRI) approach to elucidate the downstream forebrain regions modulated by activating a region of the cerebellum that induces stereotypical, ipsilateral forelimb movements. We demonstrate with ofMRI, that activating this forelimb motor region of the cerebellar cortex results in functional activation of a variety of forebrain and midbrain areas of the brain, including the hippocampus and primary motor, retrosplenial and anterior cingulate cortices. We further validate these findings using optogenetic stimulation paired with multi-electrode array recordings and post-hoc staining for molecular markers of activated neurons (i.e. c-Fos). Together, these findings demonstrate that a single discrete region of the cerebellar cortex is capable of influencing motor output and the activity of a number of downstream forebrain as well as midbrain regions thought to be involved in different aspects of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.
Intraparenchymal papillary meningioma of brainstem: case report and literature review

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Jiang Xiao-Bing

2012-01-01

Full Text Available Abstract Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment, the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.
Β-amyloid 1-42 oligomers impair function of human embryonic stem cell-derived forebrain cholinergic neurons.

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Linn Wicklund

Full Text Available Cognitive impairment in Alzheimer's disease (AD patients is associated with a decline in the levels of growth factors, impairment of axonal transport and marked degeneration of basal forebrain cholinergic neurons (BFCNs. Neurogenesis persists in the adult human brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in neurodegenerative diseases such as AD. Currently, it is still not clear how the pathophysiological environment in the AD brain affects stem cell biology. Previous studies investigating the effects of the β-amyloid (Aβ peptide on neurogenesis have been inconclusive, since both neurogenic and neurotoxic effects on progenitor cell populations have been reported. In this study, we treated pluripotent human embryonic stem (hES cells with nerve growth factor (NGF as well as with fibrillar and oligomeric Aβ1-40 and Aβ1-42 (nM-µM concentrations and thereafter studied the differentiation in vitro during 28-35 days. The process applied real time quantitative PCR, immunocytochemistry as well as functional studies of intracellular calcium signaling. Treatment with NGF promoted the differentiation into functionally mature BFCNs. In comparison to untreated cells, oligomeric Aβ1-40 increased the number of functional neurons, whereas oligomeric Aβ1-42 suppressed the number of functional neurons. Interestingly, oligomeric Aβ exposure did not influence the number of hES cell-derived neurons compared with untreated cells, while in contrast fibrillar Aβ1-40 and Aβ1-42 induced gliogenesis. These findings indicate that Aβ1-42 oligomers may impair the function of stem cell-derived neurons. We propose that it may be possible for future AD therapies to promote the maturation of functional stem cell-derived neurons by altering the brain microenvironment with trophic support and by targeting different aggregation forms of Aβ.
The Structural, Functional and Molecular Organization of the Brainstem

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Rudolf eNieuwenhuys

2011-06-01

Full Text Available According to Wilhelm His (1891, 1893 the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature and the ventral basal plate (motor in nature. Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this ‘four-functional-zones’ concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1 the magnocellular vestibular nucleus situated in the viscerosensory zone; (2 the basal plate containing a number of evidently non-motor centres (superior and inferior olives. Nevertheless the ‘functional zonal model’ has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioural profiles, as ‘local hypertrophies’ of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units.
Interictal dysfunction of a brainstem descending modulatory center in migraine patients.

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Eric A Moulton

Full Text Available The brainstem contains descending circuitry that can modulate nociceptive processing (neural signals associated with pain in the dorsal horn of the spinal cord and the medullary dorsal horn. In migraineurs, abnormal brainstem function during attacks suggest that dysfunction of descending modulation may facilitate migraine attacks, either by reducing descending inhibition or increasing facilitation. To determine whether a brainstem dysfunction could play a role in facilitating migraine attacks, we measured brainstem function in migraineurs when they were not having an attack (i.e. the interictal phase.Using fMRI (functional magnetic resonance imaging, we mapped brainstem activity to heat stimuli in 12 episodic migraine patients during the interictal phase. Separate scans were collected to measure responses to 41 degrees C and noxious heat (pain threshold+1 degrees C. Stimuli were either applied to the forehead on the affected side (as reported during an attack or the dorsum of the hand. This was repeated in 12 age-gender-matched control subjects, and the side tested corresponded to that in the matched migraine patients. Nucleus cuneiformis (NCF, a component of brainstem pain modulatory circuits, appears to be hypofunctional in migraineurs. 3 out of the 4 thermal stimulus conditions showed significantly greater NCF activation in control subjects than the migraine patients.Altered descending modulation has been postulated to contribute to migraine, leading to loss of inhibition or enhanced facilitation resulting in hyperexcitability of trigeminovascular neurons. NCF function could potentially serve as a diagnostic measure in migraine patients, even when not experiencing an attack. This has important implications for the evaluation of therapies for migraine.
Intrinsic brainstem schwannoma – A rare clinical entity and a histological enigma

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Anil Kumar Sharma

2016-01-01

Full Text Available Intraparenchymal schwannomas arising in the brainstem are very rare, and only eight cases have been reported in literature till now. We report an intraparenchymal brainstem schwannoma presenting with the classical clinical presentation of an intrinsic brainstem lesion, and discuss its clinicoradiological characteristics and histological origins. We highlight the importance of an intraoperative frozen section diagnosis in such cases. Intraoperative tissue diagnosis significantly may alter the surgical strategy, which should be aimed at near total intracapsular decompression of the schwannoma.
A pathway in the brainstem for roll-tilt of the subjective visual vertical: evidence from a lesion-behavior mapping study.

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Baier, Bernhard; Thömke, Frank; Wilting, Janine; Heinze, Caroline; Geber, Christian; Dieterich, Marianne

2012-10-24

The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion-behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucleus of Cajal. Thus, these structures constitute the anatomical pathway in the brainstem for verticality perception. Present data indicate that graviceptive otolith signals present a predominant role in the multisensory system of verticality perception.
Morphometric Studies Of The Cerebellum And Forebrain Of The ...

African Journals Online (AJOL)

Morphometric studies were undertaken using the brains of six African giant rats. The mean of weights and lengths (tip of the olfactory bulb to the caudal border of the cerebellum) were observed tobe 4.88 0.183g and 4.40 0.193g, respectively. Similarly, the mean weight and length of the cerebellum and the forebrain ...

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

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Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869
In vitro delineation of human brain-stem anatomy using a small resonator: correlation with macroscopic and histological findings

International Nuclear Information System (INIS)

Maeurer, J.; Mitrovic, T.; Knollmann, F.D.; Luedtke, E.; Requardt

1996-01-01

Our purpose was to investigate the potential of an experimental animal coil using a commercial MRI unit to delineate the anatomical structure of the human brain stem. Three formaldehyde-fixed brain-stem specimens were examined by MRI and sectioned perpendicular to their longitudinal axis. The images were compared with gross anatomy and myelin-stained histological sections. Fibre tracts and nuclei which were not evident on examination of the unstained specimen were readily identified by MRI. Due to its inherent grey/white matter contrast, MRI with a high-resolution coil delineates anatomical structures in a way comparable to the myelin-stained histological sections. However, pigmented structures, readily visible on examination of the unstained specimen were discernible on neither MRI nor on myelin-stained sections. The excellent anatomical detail and grey/white matter contrast provided by these images could make MRI a useful adjunct to the pathologist investigating brain disease. (orig.)
Effects of Caffeine on Auditory Brainstem Response

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Saleheh Soleimanian

2008-06-01

Full Text Available Background and Aim: Blocking of the adenosine receptor in central nervous system by caffeine can lead to increasing the level of neurotransmitters like glutamate. As the adenosine receptors are present in almost all brain areas like central auditory pathway, it seems caffeine can change conduction in this way. The purpose of this study was to evaluate the effects of caffeine on latency and amplitude of auditory brainstem response(ABR.Materials and Methods: In this clinical trial study 43 normal 18-25 years old male students were participated. The subjects consumed 0, 2 and 3 mg/kg BW caffeine in three different sessions. Auditory brainstem responses were recorded before and 30 minute after caffeine consumption. The results were analyzed by Friedman and Wilcoxone test to assess the effects of caffeine on auditory brainstem response.Results: Compared to control group the latencies of waves III,V and I-V interpeak interval of the cases decreased significantly after 2 and 3mg/kg BW caffeine consumption. Wave I latency significantly decreased after 3mg/kg BW caffeine consumption(p<0.01. Conclusion: Increasing of the glutamate level resulted from the adenosine receptor blocking brings about changes in conduction in the central auditory pathway.
Age-Related Changes in Binaural Interaction at Brainstem Level.

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Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Beynon, Andy J; Dhooge, Ingeborg J M

2016-01-01

Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.
Diffusion tensor imaging of the brainstem in children with achondroplasia.

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Bosemani, Thangamadhan; Orman, Gunes; Carson, Kathryn A; Meoded, Avner; Huisman, Thierry A G M; Poretti, Andrea

2014-11-01

The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In
A Clinical Research Study of Cognitive Dysfunction and Affective Impairment after Isolated Brainstem Stroke

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Fu, Xiujuan; Lu, Zuneng; Wang, Yan; Huang, Lifang; Wang, Xi; Zhang, Hong; Xiao, Zheman

2017-01-01

Although the function of the cerebellum in neurocognition has been well-documented, the similar role of the brainstem has yet to be fully elucidated. This clinical research study aimed to combine data relating to neuropsychological assessments and P300 to explore cognitive dysfunction and affective impairment following brainstem stroke. Thirty-four patients with isolated brainstem stroke and twenty-six healthy controls were recruited; for each patient, we collated data pertaining to the P300, Addenbrooke's Cognitive Examination III (ACE-III), Montreal Cognitive Assessment Chinese version (MoCA), trail-making test (TMT), Symbol Digit Modalities Test (SDMT), Wechsler Adult Intelligence Scale-Digit Spans (DS), Stroop test, Self Rating Depression Scale (SDS), and Self Rating Anxiety Scale (SAS). Significance was analyzed using an independent T-test or the Mann-Whitney U-test. Correlation was analyzed using Pearson's correlation analysis or Spearman's correlation analysis. Collectively, data revealed that brainstem stroke caused mild cognitive impairment (MCI), and that visuospatial, attention, linguistic, and emotional disturbances may occur after isolated brainstem stroke. Cognitive decline was linked to P300 latency, ACE-III, and MoCA; P300 latency was correlated with ACE-III. Patients with right brainstem lesions were more likely to suffer memory decline. The present study provides initial data relating to the role of the brainstem in neurocognition, and will be useful for further understanding of vascular cognitive and affective impairment. PMID:29311895
A Clinical Research Study of Cognitive Dysfunction and Affective Impairment after Isolated Brainstem Stroke

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Xiujuan Fu

2017-12-01

Full Text Available Although the function of the cerebellum in neurocognition has been well-documented, the similar role of the brainstem has yet to be fully elucidated. This clinical research study aimed to combine data relating to neuropsychological assessments and P300 to explore cognitive dysfunction and affective impairment following brainstem stroke. Thirty-four patients with isolated brainstem stroke and twenty-six healthy controls were recruited; for each patient, we collated data pertaining to the P300, Addenbrooke's Cognitive Examination III (ACE-III, Montreal Cognitive Assessment Chinese version (MoCA, trail-making test (TMT, Symbol Digit Modalities Test (SDMT, Wechsler Adult Intelligence Scale-Digit Spans (DS, Stroop test, Self Rating Depression Scale (SDS, and Self Rating Anxiety Scale (SAS. Significance was analyzed using an independent T-test or the Mann-Whitney U-test. Correlation was analyzed using Pearson's correlation analysis or Spearman's correlation analysis. Collectively, data revealed that brainstem stroke caused mild cognitive impairment (MCI, and that visuospatial, attention, linguistic, and emotional disturbances may occur after isolated brainstem stroke. Cognitive decline was linked to P300 latency, ACE-III, and MoCA; P300 latency was correlated with ACE-III. Patients with right brainstem lesions were more likely to suffer memory decline. The present study provides initial data relating to the role of the brainstem in neurocognition, and will be useful for further understanding of vascular cognitive and affective impairment.
Vestibular myogenic and acoustical brainstem evoked potentials in neurological practice

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O. S. Korepina

2012-01-01

Full Text Available Along with the inspection of acoustical cortex and brainstem EP in neurologic, otoneurologic and audiologic practice recently start to use so-called vestibular evoked myogenic potentials (VEMP. It is shown, that at ear stimulation by a loud sound and record of sterno-cleidomastoid contraction is possible to estimate function of the inferior vestibular nerve and vestibulospinal pathways, a sacculo-cervical reflex. In article some methodical and clinical questions of application of these kinds are presented. Combine research acoustic brainstem EP and VEMP allows to confirm effectively lesions of acoustical and vestibular ways at brainstem. The conclusion becomes, that this kind of inspection is important for revealing demielinisation and defeats in vestibulospinal tract, that quite often happens at MS, and at estimation of efficiency of treatment
The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

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Klump, Georg M.; Tollin, Daniel J.

2016-01-01

The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077
Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

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Peñas-Cazorla, Raúl; Vilaró, M Teresa

2015-11-01

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.
Brainstem encoding of speech and musical stimuli in congenital amusia: Evidence from Cantonese speakers

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Fang eLiu

2015-01-01

Full Text Available Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB, and two cello tones in quiet while their frequency-following responses (FFRs to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain.
Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers.

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Liu, Fang; Maggu, Akshay R; Lau, Joseph C Y; Wong, Patrick C M

2014-01-01

Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain.
Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers

Science.gov (United States)

Liu, Fang; Maggu, Akshay R.; Lau, Joseph C. Y.; Wong, Patrick C. M.

2015-01-01

Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain. PMID:25646077
Ontogenetic distribution of the transcription factor Nkx2.2 in the developing forebrain of Xenopus laevis

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Laura eDominguez

2011-03-01

Full Text Available The expression of the Nkx2.2 gene is involved in the organization of the alar-basal boundary in the forebrain of vertebrates. Its expression in different diencephalic and telencephalic regions, helped to define distinct progenitor domains in mouse and chick. Here we investigated the pattern of Nkx2.2 protein distribution throughout the development of the forebrain of the anuran amphibian, Xenopus laevis. We used immunohistochemical and in situ hybridization techniques for its detection in combination with other essential territorial markers in the forebrain. No expression was observed in the telencephalon. In the alar hypothalamus, Nkx2.2 positive cells were scattered in the suprachiasmatic territory, but also in the supraoptoparaventricular area, as defined by the expression of the transcription factor Otp and the lack of xDll4. In the basal hypothalamus Nkx2.2 expressing cells were localized in the tuberal region, with the exception of the arcuate nucleus, rich in Otp expressing cells. In the diencephalon it was expressed in all three prosomeres (P1-P3 and not in the zona limitans intrathalamica. The presence of Nkx2.2 expressing cells in P3 was restricted to the alar portion, as well as in prosomere P2, whereas in P1 the Nkx2.2 expressing cells were located in the basal plate and identified the alar/basal boundary. These results showed that Nkx2.2 and Sonic hedgehog are expressed in parallel adjacent stripes along the anterior-posterior axis. The results of this study showed a conserved distribution pattern of Nkx2.2 among vertebrates, crucial to recognize subdivisions that are otherwise indistinct, and supported the relevance of this transcription factor in the organization of the forebrain, particularly in the delineation of the alar/basal boundary of the forebrain.
Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

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Reyes, Beverly A S; Van Bockstaele, Elisabeth J

2006-10-30

The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.
Investigation of auditory brainstem function in elderly diabetic patients with presbycusis.

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Kovacií, Jelena; Lajtman, Zoran; Ozegović, Ivan; Knezević, Predrag; Carić, Tomislav; Vlasić, Ana

2009-01-01

We performed brainstem auditory evoked potential (BAEP) examinations in 100 patients older than 60 years and having type I diabetes mellitus and presbycusis. The aim of our investigation was to compare the BAEP results of this group with those of healthy controls with presbycusis and to look for possible correlations between alteration of the auditory brainstem function and the aging of elderly diabetic patients. Absolute and interpeak latencies of all waves were prolonged significantly in the study group of diabetic patients. The amplitudes of all waves I through V were diminished in the study group as compared to those in the control group, with statistical significance present for all waves. Analysis of the latencies (waves I, II, I, and V), interpeak latencies (I-V), and amplitudes (I, II, III, and V) of BAEP revealed a significant difference between those of diabetics and those of healthy elderly controls with presbycusis. These data support a hypothesis that there is a brainstem neuropathy in diabetes mellitus that can be assessed with auditory brainstem response testing even in the group of elderly patients with sensorineural hearing loss.
The development of sleep-wake rhythms and the search for elemental circuits in the infant brain.

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Blumberg, Mark S; Gall, Andrew J; Todd, William D

2014-06-01

Despite the predominance of sleep in early infancy, developmental science has yet to play a major role in shaping concepts and theories about sleep and its associated ultradian and circadian rhythms. Here we argue that developmental analyses help us to elucidate the relative contributions of the brainstem and forebrain to sleep-wake control and to dissect the neural components of sleep-wake rhythms. Developmental analysis also makes it clear that sleep-wake processes in infants are the foundation for those of adults. For example, the infant brainstem alone contains a fundamental sleep-wake circuit that is sufficient to produce transitions among wakefulness, quiet sleep, and active sleep. In addition, consistent with the requirements of a "flip-flop" model of sleep-wake processes, this brainstem circuit supports rapid transitions between states. Later in development, strengthening bidirectional interactions between the brainstem and forebrain contribute to the consolidation of sleep and wake bouts, the elaboration of sleep homeostatic processes, and the emergence of diurnal or nocturnal circadian rhythms. The developmental perspective promoted here critically constrains theories of sleep-wake control and provides a needed framework for the creation of fully realized computational models. Finally, with a better understanding of how this system is constructed developmentally, we will gain insight into the processes that govern its disintegration due to aging and disease.
Effects of repetitive audiogenic stimulation on open field activity in audiogenic sensitive and non-sensitive wag/rij rats

NARCIS (Netherlands)

Bikbaev, A.F.; Balabanov, D.V.; Sadovnikov, S.V.; Karpova, A.V.; Luijtelaar, E.L.J.M. van; Luijtelaar, E.L.J.M. van; Kuznetsova, G.D.; Coenen, A.M.L.; Chepurnov, S.A.

2004-01-01

A certain part of WAG/Rij rats combines genetically predisposed absence epilepsy with susceptibility to the development of audiogenic seizures. Repeated sound stimulation leads in audiogenic susceptible rats to propagation of epileptic discharges from the brainstem to the forebrain and neocortex. In
Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

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Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

2018-05-17

Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Habenula functional resting-state connectivity in pediatric CRPS.

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Erpelding, Nathalie; Sava, Simona; Simons, Laura E; Lebel, Alyssa; Serrano, Paul; Becerra, Lino; Borsook, David

2014-01-01

The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10-17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

Stance disturbance in multiple sclerosis: brainstem lesions and posturographic assessment

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Peter Schalek

2012-01-01

Full Text Available
Background. Balance disorders are commonly evidenced during the course of multiple sclerosis (MS. The aim of this study is to report characteristics of MS patient stance control disorders, measured by means of posturography and related to the brainstem lesions.

Methods. Thirty-eight patients affected by MS, mildly to moderately disable according to Kurtzke’s Expanded Disability Status Scale, underwent a complete clinical neurological and vestibular evaluation and brain MRI scanning. All patients were then tested on a static posturography platform (Tetrax, Israel in four conditions: eyes open and closed standing on a firm surface and on a foam pad.

Results. Clinical and/or MRI evidence of brainstem involvement was observed in 55.3 % of patients. When brainstem lesion was detected, Fourier analysis showed a typical pattern characterized by inversion of the 0- 0.1 Hz and 0.1 - 0.25 Hz. frequency bands.

Conclusions. MS leads to pervasive postural disturbances in the majority of subjects, including the visuo-vestibular loops and proprioception involving vestibulo-spinal pathways in at least 55.3 % of patients. Our results may also suggest the presence of Fourier inversion in patients with brainstem lesions.
Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

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Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
Effect of basal forebrain stimulation on extracellular acetylcholine release and blood flow in the olfactory bulb.

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Uchida, Sae; Kagitani, Fusako

2017-05-12

The olfactory bulb receives cholinergic basal forebrain input, as does the neocortex; however, the in vivo physiological functions regarding the release of extracellular acetylcholine and regulation of regional blood flow in the olfactory bulb are unclear. We used in vivo microdialysis to measure the extracellular acetylcholine levels in the olfactory bulb of urethane-anesthetized rats. Focal chemical stimulation by microinjection of L-glutamate into the horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain, which is the main source of cholinergic input to the olfactory bulb, increased extracellular acetylcholine release in the ipsilateral olfactory bulb. When the regional cerebral blood flow was measured using laser speckle contrast imaging, the focal chemical stimulation of the HDB did not significantly alter the blood flow in the olfactory bulb, while increases were observed in the neocortex. Our results suggest a functional difference between the olfactory bulb and neocortex regarding cerebral blood flow regulation through the release of acetylcholine by cholinergic basal forebrain input.
Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

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Dejanovic, Bratislav; Stevanovic, Ivana; Ninkovic, Milica; Stojanovic, Ivana; Lavrnja, Irena; Radicevic, Tatjana; Pavlovic, Milos

2016-03-01

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.
Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex

OpenAIRE

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2015-01-01

Purpose Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused ...
Hierarchical prediction errors in midbrain and basal forebrain during sensory learning.

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Iglesias, Sandra; Mathys, Christoph; Brodersen, Kay H; Kasper, Lars; Piccirelli, Marco; den Ouden, Hanneke E M; Stephan, Klaas E

2013-10-16

In Bayesian brain theories, hierarchically related prediction errors (PEs) play a central role for predicting sensory inputs and inferring their underlying causes, e.g., the probabilistic structure of the environment and its volatility. Notably, PEs at different hierarchical levels may be encoded by different neuromodulatory transmitters. Here, we tested this possibility in computational fMRI studies of audio-visual learning. Using a hierarchical Bayesian model, we found that low-level PEs about visual stimulus outcome were reflected by widespread activity in visual and supramodal areas but also in the midbrain. In contrast, high-level PEs about stimulus probabilities were encoded by the basal forebrain. These findings were replicated in two groups of healthy volunteers. While our fMRI measures do not reveal the exact neuron types activated in midbrain and basal forebrain, they suggest a dichotomy between neuromodulatory systems, linking dopamine to low-level PEs about stimulus outcome and acetylcholine to more abstract PEs about stimulus probabilities. Copyright © 2013 Elsevier Inc. All rights reserved.
Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

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Renata Mota Mamede de Carvallo

2008-09-01

Full Text Available Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU, as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests could be applied to all babies. The “pass” result for the group of babies from the nursery was 94.7% using Transient Evoked Otoacoustic Emissions and 96% using Automatic Auditory Brainstem Response. The newborn intensive care unit group obtained 87.1% on Transient Evoked Otoacoustic Emissions and 80% on the Automatic Auditory Brainstem Response, and there was no statistical difference between the procedures when the groups were evaluated individually. However, comparing the groups, Transient Evoked Otoacoustic Emissions were presented in 94.7% of the nursery babies and in 87.1% in the group from the newborn intensive care unit. Considering the Automatic Auditory Brainstem Response, we found 96 and 87%, respectively. Cconclusions: Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response had similar “pass” and “fail” results when the procedures were applied to neonates from the regular nursery, and the combined tests were more precise to detect hearing impairment in the newborn intensive care unit babies.
Optimal technique of linear accelerator-based stereotactic radiosurgery for tumors adjacent to brainstem.

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Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih

2016-01-01

Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)-based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups-1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem. Copyright © 2016 American Association of Medical Dosimetrists. All rights reserved.
Stereotactic radiosurgery for brainstem metastases: Survival, tumor control, and patient outcomes

International Nuclear Information System (INIS)

Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.; Pollock, Bruce E.

2007-01-01

Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival time after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS
Dyslexia risk gene relates to representation of sound in the auditory brainstem.

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Neef, Nicole E; Müller, Bent; Liebig, Johanna; Schaadt, Gesa; Grigutsch, Maren; Gunter, Thomas C; Wilcke, Arndt; Kirsten, Holger; Skeide, Michael A; Kraft, Indra; Kraus, Nina; Emmrich, Frank; Brauer, Jens; Boltze, Johannes; Friederici, Angela D

2017-04-01

Dyslexia is a reading disorder with strong associations with KIAA0319 and DCDC2. Both genes play a functional role in spike time precision of neurons. Strikingly, poor readers show an imprecise encoding of fast transients of speech in the auditory brainstem. Whether dyslexia risk genes are related to the quality of sound encoding in the auditory brainstem remains to be investigated. Here, we quantified the response consistency of speech-evoked brainstem responses to the acoustically presented syllable [da] in 159 genotyped, literate and preliterate children. When controlling for age, sex, familial risk and intelligence, partial correlation analyses associated a higher dyslexia risk loading with KIAA0319 with noisier responses. In contrast, a higher risk loading with DCDC2 was associated with a trend towards more stable responses. These results suggest that unstable representation of sound, and thus, reduced neural discrimination ability of stop consonants, occurred in genotypes carrying a higher amount of KIAA0319 risk alleles. Current data provide the first evidence that the dyslexia-associated gene KIAA0319 can alter brainstem responses and impair phoneme processing in the auditory brainstem. This brain-gene relationship provides insight into the complex relationships between phenotype and genotype thereby improving the understanding of the dyslexia-inherent complex multifactorial condition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin.

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do Carmo, J M; da Silva, A A; Sessums, P O; Ebaady, S H; Pace, B R; Rushing, J S; Davis, M T; Hall, J E

2014-06-01

We examined whether deficiency of Src homology 2 containing phosphatase (Shp2) signaling in forebrain neurons alters metabolic and cardiovascular regulation under various conditions and if it attenuates the anorexic and cardiovascular effects of leptin. We also tested whether forebrain Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute stress. Forebrain Shp2(-/-) mice were generated by crossing Shp2(flox/flox) mice with CamKIIα-cre mice. At 22-24 weeks of age, the mice were instrumented for telemetry for measurement of BP, HR and body temperature (BT). Oxygen consumption (VO2), energy expenditure and motor activity were monitored by indirect calorimetry. Shp2/CamKIIα-cre mice were heavier (46±3 vs 32±1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic and hyperphagic compared to Shp2(flox/flox) control mice. Shp2/CamKIIα-cre mice exhibited reduced food intake responses to fasting/refeeding and impaired regulation of BT when exposed to 15 and 30 °C ambient temperatures. Despite being obese and having many features of metabolic syndrome, Shp2/CamKIIα-cre mice had similar daily average BP and HR compared to Shp2(flox/flox) mice (112±2 vs 113±1 mm Hg and 595±34 vs 650±40 b.p.m.), but exhibited increased BP and HR responses to cold exposure and acute air-jet stress test. Leptin's ability to reduce food intake and to raise BP were markedly attenuated in Shp2/CamKIIα-cre mice. These results suggest that forebrain Shp2 signaling regulates food intake, appetite responses to caloric deprivation and thermogenic control of body temperature during variations in ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated with augmented cardiovascular responses to cold and acute stress but attenuated BP responses to leptin.
Optimization behavior of brainstem respiratory neurons. A cerebral neural network model.

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Poon, C S

1991-01-01

A recent model of respiratory control suggested that the steady-state respiratory responses to CO2 and exercise may be governed by an optimal control law in the brainstem respiratory neurons. It was not certain, however, whether such complex optimization behavior could be accomplished by a realistic biological neural network. To test this hypothesis, we developed a hybrid computer-neural model in which the dynamics of the lung, brain and other tissue compartments were simulated on a digital computer. Mimicking the "controller" was a human subject who pedalled on a bicycle with varying speed (analog of ventilatory output) with a view to minimize an analog signal of the total cost of breathing (chemical and mechanical) which was computed interactively and displayed on an oscilloscope. In this manner, the visuomotor cortex served as a proxy (homolog) of the brainstem respiratory neurons in the model. Results in 4 subjects showed a linear steady-state ventilatory CO2 response to arterial PCO2 during simulated CO2 inhalation and a nearly isocapnic steady-state response during simulated exercise. Thus, neural optimization is a plausible mechanism for respiratory control during exercise and can be achieved by a neural network with cognitive computational ability without the need for an exercise stimulus.
Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

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Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

2014-01-01

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...
Combined CMV- and HSV-1 brainstem encephalitis restricted to medulla oblongata.

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Katchanov, J; Branding, G; Stocker, H

2014-04-15

We report a very rare case of a combined CMV- and HSV-1 isolated brainstem encephalitis restricted to medulla oblongata in a patient with advanced HIV disease. Neither limbic nor general ventricular involvement was detected on neuroimaging. The case highlights the importance of testing for HSV-1 and CMV in HIV-infected patients presenting with an isolated brainstem syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.
The anorectic actions of the TGFβ cytokine MIC-1/GDF15 require an intact brainstem area postrema and nucleus of the solitary tract.

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Vicky Wang-Wei Tsai

Full Text Available Macrophage inhibitory cytokine-1 (MIC-1/GDF15 modulates food intake and body weight under physiological and pathological conditions by acting on the hypothalamus and brainstem. When overexpressed in disease, such as in advanced cancer, elevated serum MIC-1/GDF15 levels lead to an anorexia/cachexia syndrome. To gain a better understanding of its actions in the brainstem we studied MIC-1/GDF15 induced neuronal activation identified by induction of Fos protein. Intraperitoneal injection of human MIC-1/GDF15 in mice activated brainstem neurons in the area postrema (AP and the medial (m portion of the nucleus of the solitary tract (NTS, which did not stain with tyrosine hydroxylase (TH. To determine the importance of these brainstem nuclei in the anorexigenic effect of MIC-1/GDF15, we ablated the AP alone or the AP and the NTS. The latter combined lesion completely reversed the anorexigenic effects of MIC-1/GDF15. Altogether, this study identified neurons in the AP and/or NTS, as being critical for the regulation of food intake and body weight by MIC-1/GDF15.
Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies

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Nanda, Ronica H., E-mail: rhazari@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia (United States); Ganju, Rohit G.; Schreibmann, Edward [Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia (United States); Chen, Zhengjia; Zhang, Chao [Department of Biostatistics and Bioinformatics Shared Resource, Winship Cancer Institute, Emory University Rollins School of Public Health, Atlanta, Georgia (United States); Jegadeesh, Naresh; Cassidy, Richard; Deng, Claudia; Eaton, Bree R.; Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University College of Medicine, Atlanta, Georgia (United States)

2017-06-01

Purpose: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. Methods and Materials: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstem receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. Results: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. Conclusion: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide
Neuromyelitis Optica Lesion Mimicking Brainstem Glioma

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J Gordon Millichap

2007-12-01

Full Text Available A 12-year-old girl who presented with weakness of the left extremities and right sided sixth cranial nerve palsy had neuromyelitis optica (NMO mistaken for brainstem glioma on MRI, in a report from Brain Research Institute, Yonsei University College of Medicine,Seoul, Republic of KoreaNeuromyelitis Optica, Optic-Spinal Syndrome, Spectroscopy.
Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

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Rothermel, Markus; Carey, Ryan M.; Puche, Adam; Shipley, Michael T.

2014-01-01

Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment. PMID:24672011
Right-sided dominance of the bilateral vestibular system in the upper brainstem and thalamus.

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Dieterich, Marianne; Kirsch, V; Brandt, T

2017-10-01

MRI diffusion tensor imaging tractography was performed on the bilateral vestibular brainstem pathways, which run from the vestibular nuclei via the paramedian and posterolateral thalamic subnuclei to the parieto-insular vestibular cortex. Twenty-one right-handed healthy subjects participated. Quantitative analysis revealed a rope-ladder-like system of vestibular pathways in the brainstem with crossings at pontine and mesencephalic levels. Three structural types of right-left fiber distributions could be delineated: (1) evenly distributed pathways at the lower pontine level from the vestibular nuclei to the pontine crossing, (2) a moderate, pontomesencephalic right-sided lateralization between the pontine and mesencephalic crossings, and (3) a further increase of the right-sided lateralization above the mesencephalic crossing leading to the thalamic vestibular subnuclei. The increasing lateralization along the brainstem was the result of an asymmetric number of pontine and mesencephalic crossing fibers which was higher for left-to-right crossings. The dominance of the right vestibular meso-diencephalic circuitry in right-handers corresponds to the right-hemispheric dominance of the vestibular cortical network. The structural asymmetry apparent in the upper brainstem might be interpreted in relation to the different functions of the vestibular system depending on their anatomical level: a symmetrical sensorimotor reflex control of eye, head, and body mediated by the lower brainstem; a lateralized right-sided upper brainstem-thalamic function as part of the dominant right-sided cortical/subcortical vestibular system that enables a global percept of body motion and orientation in space.
The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain.

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Frankel, Paul S; Cunningham, Kathryn A

2002-12-27

The hallucinogen d-lysergic acid diethylamide (d-LSD) evokes dramatic somatic and psychological effects. In order to analyze the neural activation induced by this unique psychoactive drug, we tested the hypothesis that expression of the immediate-early gene product c-Fos is induced in specific regions of the rat forebrain by a relatively low, behaviorally active, dose of d-LSD (0.16 mg/kg, i.p.); c-Fos protein expression was assessed at 30 min, and 1, 2 and 4 h following d-LSD injection. A time- and region-dependent expression of c-Fos was observed with a significant increase (PLSD administration. These data demonstrate a unique pattern of c-Fos expression in the rat forebrain following a relatively low dose of d-LSD and suggest that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD. Copyright 2002 Elsevier Science B.V.

Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity

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Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Lee, Cheng-Chia [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Kano, Hideyuki; Cohen, Jonathan [Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Janopaul-Naylor, James; Alonso-Basanta, Michelle; Lee, John Y.K. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Simonova, Gabriela; Liscak, Roman [Department of Radiation and Stereotactic Neurosurgery, Na Homolce Hospital, Prague (Czech Republic); Wolf, Amparo; Kvint, Svetlana [Department of Neurosurgery, New York University Lagone Medical Center, New York, New York (United States); Grills, Inga S.; Johnson, Matthew [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Liu, Kang-Du; Lin, Chung-Jung [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Mathieu, David; Héroux, France [Division of Neurosurgery, Université de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Québec (Canada); Silva, Danilo; Sharma, Mayur [Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (United States); Cifarelli, Christopher P. [Departments of Neurosurgery and Radiation Oncology, West Virginia University, Morgantown, West Virginia (United States); and others

2016-10-01

Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.
Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation.

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Wang, Jun Yi; Hessl, David; Hagerman, Randi J; Simon, Tony J; Tassone, Flora; Ferrer, Emilio; Rivera, Susan M

2017-07-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective. Copyright © 2017 Elsevier Inc. All rights reserved.
Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration.

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McBrayer, Zofeyah L; Dimova, Jiva; Pisansky, Marc T; Sun, Mu; Beppu, Hideyuki; Gewirtz, Jonathan C; O'Connor, Michael B

2015-01-01

To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.
Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration.

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Zofeyah L McBrayer

Full Text Available To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.
Stereotactic radiosurgery for deep intracranial arteriovenous malformations, part 1: Brainstem arteriovenous malformations.

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Cohen-Inbar, Or; Ding, Dale; Chen, Ching-Jen; Sheehan, Jason P

2016-02-01

The management of brainstem arteriovenous malformations (AVM) are one of the greatest challenges encountered by neurosurgeons. Brainstem AVM have a higher risk of hemorrhage compared to AVM in other locations, and rupture of these lesions commonly results in devastating neurological morbidity and mortality. The potential morbidity associated with currently available treatment modalities further compounds the complexity of decision making for affected patients. Stereotactic radiosurgery (SRS) has an important role in the management of brainstem AVM. SRS offers acceptable obliteration rates with lower risks of hemorrhage occurring during the latency period. Complex nidal architecture requires a multi-disciplinary treatment approach. Nidi partly involving subpial/epipial regions of the dorsal midbrain or cerebellopontine angle should be considered for a combination of endovascular embolization, micro-surgical resection and SRS. Considering the fact that incompletely obliterated lesions (even when reduced in size) could still cause lethal hemorrhages, additional treatment, including repeat SRS and surgical resection should be considered when complete obliteration is not achieved by first SRS. Patients with brainstem AVM require continued clinical and radiological observation and follow-up after SRS, well after angiographic obliteration has been confirmed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration

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William Sealy Hambright

2017-08-01

Full Text Available Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD; however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus that are severely afflicted in AD patients might be vulnerable to ferroptosis. To this end, we generated Gpx4BIKO mouse, a mouse model with conditional deletion in forebrain neurons of glutathione peroxidase 4 (Gpx4, a key regulator of ferroptosis, and showed that treatment with tamoxifen led to deletion of Gpx4 primarily in forebrain neurons of adult Gpx4BIKO mice. Starting at 12 weeks after tamoxifen treatment, Gpx4BIKO mice exhibited significant deficits in spatial learning and memory function versus Control mice as determined by the Morris water maze task. Further examinations revealed that the cognitively impaired Gpx4BIKO mice exhibited hippocampal neurodegeneration. Notably, markers associated with ferroptosis, such as elevated lipid peroxidation, ERK activation and augmented neuroinflammation, were observed in Gpx4BIKO mice. We also showed that Gpx4BIKO mice fed a diet deficient in vitamin E, a lipid soluble antioxidant with anti-ferroptosis activity, had an expedited rate of hippocampal neurodegeneration and behavior dysfunction, and that treatment with a small-molecule ferroptosis inhibitor ameliorated neurodegeneration in those mice. Taken together, our results indicate that forebrain neurons are susceptible to ferroptosis, suggesting that ferroptosis may be an important neurodegenerative mechanism in diseases such as AD. Keywords: Ferroptosis, Neurodegeneration, Cognitive impairment, Alzheimer's disease, Glutathione peroxidase 4, Transgenic mice
Evaluation of peripheral auditory pathways and brainstem in obstructive sleep apnea

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Erika Matsumura

Full Text Available Abstract Introduction Obstructive sleep apnea causes changes in normal sleep architecture, fragmenting it chronically with intermittent hypoxia, leading to serious health consequences in the long term. It is believed that the occurrence of respiratory events during sleep, such as apnea and hypopnea, can impair the transmission of nerve impulses along the auditory pathway that are highly dependent on the supply of oxygen. However, this association is not well established in the literature. Objective To compare the evaluation of peripheral auditory pathway and brainstem among individuals with and without obstructive sleep apnea. Methods The sample consisted of 38 adult males, mean age of 35.8 (±7.2, divided into four groups matched for age and Body Mass Index. The groups were classified based on polysomnography in: control (n = 10, mild obstructive sleep apnea (n = 11 moderate obstructive sleep apnea (n = 8 and severe obstructive sleep apnea (n = 9. All study subjects denied a history of risk for hearing loss and underwent audiometry, tympanometry, acoustic reflex and Brainstem Auditory Evoked Response. Statistical analyses were performed using three-factor ANOVA, 2-factor ANOVA, chi-square test, and Fisher's exact test. The significance level for all tests was 5%. Results There was no difference between the groups for hearing thresholds, tympanometry and evaluated Brainstem Auditory Evoked Response parameters. An association was observed between the presence of obstructive sleep apnea and changes in absolute latency of wave V (p = 0.03. There was an association between moderate obstructive sleep apnea and change of the latency of wave V (p = 0.01. Conclusion The presence of obstructive sleep apnea is associated with changes in nerve conduction of acoustic stimuli in the auditory pathway in the brainstem. The increase in obstructive sleep apnea severity does not promote worsening of responses assessed by audiometry, tympanometry and Brainstem
Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.

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Jingxia Gao

Full Text Available The guidance receptor DCC (deleted in colorectal cancer ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.
Developmental study of vitamin C distribution in children's brainstems by immunohistochemistry.

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Coveñas, R; González-Fuentes, J; Rivas-Infante, E; Lagartos-Donate, M J; Mangas, A; Geffard, M; Arroyo-Jiménez, M M; Cebada-Sánchez, S; Insausti, R; Marcos, P

2015-09-01

Vitamin C (Vit C) is an important antioxidant, exerts powerful neuroprotective brain effects and plays a role in neuronal development and maturation. Vit C is present in brain tissue at higher concentrations than in other organs, but its detailed distribution in brain is unknown. Immunohistochemical detection of this vitamin has been performed by using a highly specific antibody against Vit C. The aim of the present work was to analyze the distribution of Vit C in children's brainstems during postnatal development, comparing two groups of ages: younger and older than one year of life. In general, the same areas showing neurons with Vit C in young cases are also immunostained at older ages. The distribution of neurons containing Vit C was broader in the brainstems of older children, suggesting that brainstem neurons maintain or even increase their ability to retain Vit C along the life span. Immunohistochemical labeling revealed only cell bodies containing this vitamin, and no immunoreactive fibers were observed. The distribution pattern of Vit C in children's brainstems suggests a possible role of Vit C in brain homeostatic regulation. In addition, the constant presence of Vit C in neurons of locus coeruleus supports the important role of Vit C in noradrenaline synthesis, which seemed to be maintained along postnatal development. Copyright © 2015 Elsevier GmbH. All rights reserved.
Presbycusis and auditory brainstem responses: a review

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Shilpa Khullar

2011-06-01

Full Text Available Age-related hearing loss or presbycusis is a complex phenomenon consisting of elevation of hearing levels as well as changes in the auditory processing. It is commonly classified into four categories depending on the cause. Auditory brainstem responses (ABRs are a type of early evoked potentials recorded within the first 10 ms of stimulation. They represent the synchronized activity of the auditory nerve and the brainstem. Some of the changes that occur in the aging auditory system may significantly influence the interpretation of the ABRs in comparison with the ABRs of the young adults. The waves of ABRs are described in terms of amplitude, latencies and interpeak latency of the different waves. There is a tendency of the amplitude to decrease and the absolute latencies to increase with advancing age but these trends are not always clear due to increase in threshold with advancing age that act a major confounding factor in the interpretation of ABRs.
Prodominant hypertensive brainstem encephalopathy with supratentorial involvement: Case report and literature review

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Kim, Ji Hee; Park, Sung Tae; Lim, Hyun Kyung [Dept. of Radiology, Soonchunhyang University Hospital, Soonchunhyang University School of Medicine, Seoul (Korea, Republic of); Kim, Sung Tae; Cha, Ji Hoon [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2014-12-15

Hypertensive encephalopathy typically presents with bilateral parietooccipital vasogenic edema. Brainstem and cerebellar edema are uncommon in association with typical supratentorial changes. We experienced three cases of atypical hypertensive encephalopathy involving brainstem and cerebellum as well as cerebral white matter, which showed characteristic alternating linear bright and low signals in the pons, the so-called 'stripe sign'. We report these cases here with a brief literature review.
Brain activation during micturition in women

NARCIS (Netherlands)

Blok, Bertil F.M.; Sturms, Leontien M.; Holstege, Gert

1998-01-01

Experiments in the cat have led to a concept of how the CNS controls micturition. In a previous study this concept was tested in a PET study in male volunteers, It was demonstrated that specific brainstem and forebrain areas are activated during micturition, It was unfortunate that this study did
Intermediate stage of sleep and acute cerveau isolé preparation in the rat.

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User, P; Gioanni, H; Gottesmann, C

1980-01-01

The acute cerveau isole rat shows spindle bursts of large amplitude alternating with low voltage activity in the frontal cortex and continuous theta rhythm in the dorsal hippocampus. These patterns closely resemble an "intermediate" stage of sleep-waking cycle, when the forebrain structures seem to be functionally disconnected from the brainstem.
Brainstem auditory evoked potentials in horses

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Juliana Almeida Nogueira da Gama

2016-04-01

Full Text Available ABSTRACT: The brainstem auditory evoked potential (BAEP evaluates the integrity of the auditory pathways to the brainstem. The aim of this study was to evoke BAEPs in 21 clinically normal horses. The animals were sedated with detomidine hydrochloride (0.013mg.kg-1 BW. Earphones were inserted and rarefaction clicks at 90 dB and noise masking at 40 dB were used. After performing the test, the latencies of waves (I, II, III, IV, and V and interpeaks(I-III, III-V, and I-V were identified. The mean latencies of the waves were as follows: wave I, 2.4 ms; wave II, 2.24 ms; wave III, 3.61ms; wave IV, 4.61ms; and wave V, 5.49ms. The mean latencies of the interpeaks were as follows: I-III, 1.37ms; III-V, 1.88ms; and I-V, 3.26ms. This is the first study using BAEPs in horses in Brazil, and the observed latencies will be used as normative data for the interpretation of tests performed on horses with changes related to auditory system or neurologic abnormalities.
Herpetic brainstem encephalitis: report of a post-mortem case studied electron microscopically and immunohisiochemically

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José Eymard Homem Pitella

1987-03-01

Full Text Available A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalea followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medula oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.
Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death

International Nuclear Information System (INIS)

Tomiyama, Ken-ichi; Funada, Masahiko

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB 1 receptor antagonist AM251, but not with the selective CB 2 receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB 1 receptor, but not by the CB 2 receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB 1 receptor, but not by the CB 2 receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB 1 receptors
Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.

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H Scott Swartzwelder

Full Text Available The long-term effects of intermittent ethanol exposure during adolescence (AIE are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30 received exposure to AIE (5g/kg, i.g. or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.
Bayesian segmentation of brainstem structures in MRI

DEFF Research Database (Denmark)

Iglesias, Juan Eugenio; Van Leemput, Koen; Bhatt, Priyanka

2015-01-01

the brainstem structures in novel scans. Thanks to the generative nature of the scheme, the segmentation method is robust to changes in MRI contrast or acquisition hardware. Using cross validation, we show that the algorithm can segment the structures in previously unseen T1 and FLAIR scans with great accuracy...
Visual training paired with electrical stimulation of the basal forebrain improves orientation-selective visual acuity in the rat.

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Kang, Jun Il; Groleau, Marianne; Dotigny, Florence; Giguère, Hugo; Vaucher, Elvire

2014-07-01

The cholinergic afferents from the basal forebrain to the primary visual cortex play a key role in visual attention and cortical plasticity. These afferent fibers modulate acute and long-term responses of visual neurons to specific stimuli. The present study evaluates whether this cholinergic modulation of visual neurons results in cortical activity and visual perception changes. Awake adult rats were exposed repeatedly for 2 weeks to an orientation-specific grating with or without coupling this visual stimulation to an electrical stimulation of the basal forebrain. The visual acuity, as measured using a visual water maze before and after the exposure to the orientation-specific grating, was increased in the group of trained rats with simultaneous basal forebrain/visual stimulation. The increase in visual acuity was not observed when visual training or basal forebrain stimulation was performed separately or when cholinergic fibers were selectively lesioned prior to the visual stimulation. The visual evoked potentials show a long-lasting increase in cortical reactivity of the primary visual cortex after coupled visual/cholinergic stimulation, as well as c-Fos immunoreactivity of both pyramidal and GABAergic interneuron. These findings demonstrate that when coupled with visual training, the cholinergic system improves visual performance for the trained orientation probably through enhancement of attentional processes and cortical plasticity in V1 related to the ratio of excitatory/inhibitory inputs. This study opens the possibility of establishing efficient rehabilitation strategies for facilitating visual capacity.
Mosaic Evolution of Brainstem Motor Nuclei in Catarrhine Primates

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Seth D. Dobson

2011-01-01

Full Text Available Facial motor nucleus volume coevolves with both social group size and primary visual cortex volume in catarrhine primates as part of a specialized neuroethological system for communication using facial expressions. Here, we examine whether facial nucleus volume also coevolves with functionally unrelated brainstem motor nuclei (trigeminal motor and hypoglossal due to developmental constraints. Using phylogenetically informed multiple regression analyses of previously published brain component data, we demonstrate that facial nucleus volume is not correlated with the volume of other motor nuclei after controlling for medulla volume. Our results show that brainstem motor nuclei can evolve independently of other developmentally linked structures in association with specific behavioral ecological conditions. This finding provides additional support for the mosaic view of brain evolution.

Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

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Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

1988-12-01

Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.
Effects of myelin or cell body brainstem lesions on 3-channel Lissajous' trajectories of feline auditory brainstem evoked potentials.

Science.gov (United States)

Pratt, H; Zaaroor, M; Bleich, N; Starr, A

1991-06-01

Auditory brainstem evoked potentials (ABEP) were recorded from 16 awake cats to obtain 3-Channel Lissajous' Trajectories (3CLTs) using three orthogonal differential electrode configurations (nasion-midline nuchal ridge, left-right mastoids, vertex-midline under the mandible). Potentials, evoked by monaural 80 dBnHL (re, human threshold) clicks, were studied before, and up to 7 weeks after inducing neuronal lesions localized to the cochlear nucleus (CN) or the superior olivary complex (SOC), or myelin lesions localized to the fibers of the trapezoid body connecting these two structures. Neuronal lesions were induced by injection of kainic acid (KA), while myelin lesions were induced by injection of L-alpha-lysophosphatidylcholine (LPC). With CN neuronal lesions the major changes in 3CLT were in the time domain of 'b', 'c' and 'd' (components P2, P3 and P4 of single-channel ABEP). With SOC neuronal lesions the major changes were in 'c' and 'd' of 3CLT (P3 and P4 of ABEP). With trapezoid body lesions the major change was in 'c' (P3 of ABEP). The results are compatible with the peripheral generation of the first ABEP components (P1a and P1b). The second component (P2) is generated by ipsilateral CN neurones and their outputs. The third component (P3) is generated primarily by ipsilateral SOC neurones and their outputs, with the ipsilateral CN providing input. The The fourth component (P4) is generated bilaterally by the SOC neurones and their outputs, receiving their inputs from ipsilateral CN. The fifth ABEP component (P5) is generated by structures central to the SOCs and their immediate outputs. Neither focal neuronal nor myelin lesions were sufficient to produce obliteration of any component, consistent with a set of generators for each of the ABEP components, consisting of both cell bodies and their output fibers, that is distributed spatially in the brainstem.
Evaluation of peripheral auditory pathways and brainstem in obstructive sleep apnea.

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Matsumura, Erika; Matas, Carla Gentile; Magliaro, Fernanda Cristina Leite; Pedreño, Raquel Meirelles; Lorenzi-Filho, Geraldo; Sanches, Seisse Gabriela Gandolfi; Carvallo, Renata Mota Mamede

2016-11-25

Obstructive sleep apnea causes changes in normal sleep architecture, fragmenting it chronically with intermittent hypoxia, leading to serious health consequences in the long term. It is believed that the occurrence of respiratory events during sleep, such as apnea and hypopnea, can impair the transmission of nerve impulses along the auditory pathway that are highly dependent on the supply of oxygen. However, this association is not well established in the literature. To compare the evaluation of peripheral auditory pathway and brainstem among individuals with and without obstructive sleep apnea. The sample consisted of 38 adult males, mean age of 35.8 (±7.2), divided into four groups matched for age and Body Mass Index. The groups were classified based on polysomnography in: control (n=10), mild obstructive sleep apnea (n=11) moderate obstructive sleep apnea (n=8) and severe obstructive sleep apnea (n=9). All study subjects denied a history of risk for hearing loss and underwent audiometry, tympanometry, acoustic reflex and Brainstem Auditory Evoked Response. Statistical analyses were performed using three-factor ANOVA, 2-factor ANOVA, chi-square test, and Fisher's exact test. The significance level for all tests was 5%. There was no difference between the groups for hearing thresholds, tympanometry and evaluated Brainstem Auditory Evoked Response parameters. An association was observed between the presence of obstructive sleep apnea and changes in absolute latency of wave V (p=0.03). There was an association between moderate obstructive sleep apnea and change of the latency of wave V (p=0.01). The presence of obstructive sleep apnea is associated with changes in nerve conduction of acoustic stimuli in the auditory pathway in the brainstem. The increase in obstructive sleep apnea severity does not promote worsening of responses assessed by audiometry, tympanometry and Brainstem Auditory Evoked Response. Copyright © 2016 Associação Brasileira de
A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

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Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn

2014-01-01

Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiat...
Brainstem Tuberculoma in Pregnancy

Directory of Open Access Journals (Sweden)

Dana A. Muin

2015-01-01

Full Text Available We report a case of a Somali refugee who presented in the second trimester of her first pregnancy with a four-week history of gradual right-sided sensomotoric hemisyndrome including facial palsy and left-sided paresis of the oculomotorius nerve causing drooping of the left eyelid and double vision. Cranial magnetic resonance imaging revealed a solitary brainstem lesion. Upon detection of hilar lymphadenopathy on chest X-ray (CXR, the diagnosis of disseminated tuberculosis with involvement of the central nervous system was confirmed by PCR and treatment induced with rifampicin, isoniazid, pyrazinamide, and ethambutol. The patient had a steady neurological improvement and a favorable pregnancy outcome.
Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB{sub 1} receptors and apoptotic cell death

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Tomiyama, Ken-ichi; Funada, Masahiko, E-mail: mfunada@ncnp.go.jp

2014-01-01

The abuse of herbal products containing synthetic cannabinoids has become an issue of public concern. The purpose of this paper was to evaluate the acute cytotoxicity of synthetic cannabinoids on mouse brain neuronal cells. Cytotoxicity induced by synthetic cannabinoid (CP-55,940, CP-47,497, CP-47,497-C8, HU-210, JWH-018, JWH-210, AM-2201, and MAM-2201) was examined using forebrain neuronal cultures. These synthetic cannabinoids induced cytotoxicity in the forebrain cultures in a concentration-dependent manner. The cytotoxicity was suppressed by preincubation with the selective CB{sub 1} receptor antagonist AM251, but not with the selective CB{sub 2} receptor antagonist AM630. Furthermore, annexin-V-positive cells were found among the treated forebrain cells. Synthetic cannabinoid treatment induced the activation of caspase-3, and preincubation with a caspase-3 inhibitor significantly suppressed the cytotoxicity. These synthetic cannabinoids induced apoptosis through a caspase-3-dependent mechanism in the forebrain cultures. Our results indicate that the cytotoxicity of synthetic cannabinoids towards primary neuronal cells is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and further suggest that caspase cascades may play an important role in the apoptosis induced by these synthetic cannabinoids. In conclusion, excessive synthetic cannabinoid abuse may present a serious acute health concern due to neuronal damage or deficits in the brain. - Highlights: • Synthetic cannabinoids (classical cannabinoids, non-classical cannabinoids, and aminoalkylindole derivatives) induce cytotoxicity in mouse forebrain cultures. • Synthetic cannabinoid-induced cytotoxicity towards forebrain cultures is mediated by the CB{sub 1} receptor, but not by the CB{sub 2} receptor, and involves caspase-dependent apoptosis. • A high concentration of synthetic cannabinoids may be toxic to neuronal cells that express CB{sub 1} receptors.
Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27

International Nuclear Information System (INIS)

Schmook, Maria T.; Weber, Michael; Kasprian, Gregor; Nemec, Stefan; Prayer, Daniela; Brugger, Peter C.; Krampl-Bettelheim, Elisabeth

2010-01-01

Forebrain malformations include some of the most severe developmental anomalies and require early diagnosis. The proof of normal or abnormal prosencephalic development may have an influence on further management in the event of a suspected fetal malformation. The purpose of this retrospective study was to evaluate the detectability of anatomical landmarks of forebrain development using in vivo fetal magnetic resonance imaging (MRI) before gestational week (gw) 27. MRI studies of 83 singleton fetuses (gw 16-26, average ±sd: gw 22 ± 2) performed at 1.5 Tesla were assessed. T2-weighted (w) fast spin echo, T1w gradient-echo and diffusion-weighted sequences were screened for the detectability of anatomical landmarks as listed below. The interhemispheric fissure, ocular bulbs, corpus callosum, infundibulum, chiasm, septum pellucidum (SP), profile, and palate were detectable in 95%, 95%, 89%, 87%, 82%, 81%, 78%, 78% of cases. Olfactory tracts were more easily delineated than bulbs and sulci (37% versus 18% and 8%), with significantly higher detection rates in the coronal plane. The pituitary gland could be detected on T1w images in 60% with an increasing diameter with gestational age (p=0.041). The delineation of olfactory tracts (coronal plane), chiasm, SP and pituitary gland were significantly increased after week 21 (p<0.05). Pathologies were found in 28% of cases. This study provides detection rates for anatomical landmarks of forebrain development with fetal MRI before gw 27. Several anatomical structures are readily detectable with routine fetal MRI sequences; thus, if these landmarks are not delineable, it should raise the suspicion of a pathology. Recommendations regarding favorable sequences/planes are provided. (orig.)
Forebrain development in fetal MRI: evaluation of anatomical landmarks before gestational week 27

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Schmook, Maria T.; Weber, Michael; Kasprian, Gregor; Nemec, Stefan; Prayer, Daniela [Medical University of Vienna, Department of Radiology/Division of Neuro- and Musculoskeletal Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Integrative Morphology Group, Center for Anatomy and Cell Biology, Vienna (Austria); Krampl-Bettelheim, Elisabeth [Department of Obstetrics and Gynecology / Division of Obstetrics and Feto-maternal Medicine, Vienna (Austria)

2010-06-15

Forebrain malformations include some of the most severe developmental anomalies and require early diagnosis. The proof of normal or abnormal prosencephalic development may have an influence on further management in the event of a suspected fetal malformation. The purpose of this retrospective study was to evaluate the detectability of anatomical landmarks of forebrain development using in vivo fetal magnetic resonance imaging (MRI) before gestational week (gw) 27. MRI studies of 83 singleton fetuses (gw 16-26, average {+-}sd: gw 22 {+-} 2) performed at 1.5 Tesla were assessed. T2-weighted (w) fast spin echo, T1w gradient-echo and diffusion-weighted sequences were screened for the detectability of anatomical landmarks as listed below. The interhemispheric fissure, ocular bulbs, corpus callosum, infundibulum, chiasm, septum pellucidum (SP), profile, and palate were detectable in 95%, 95%, 89%, 87%, 82%, 81%, 78%, 78% of cases. Olfactory tracts were more easily delineated than bulbs and sulci (37% versus 18% and 8%), with significantly higher detection rates in the coronal plane. The pituitary gland could be detected on T1w images in 60% with an increasing diameter with gestational age (p=0.041). The delineation of olfactory tracts (coronal plane), chiasm, SP and pituitary gland were significantly increased after week 21 (p<0.05). Pathologies were found in 28% of cases. This study provides detection rates for anatomical landmarks of forebrain development with fetal MRI before gw 27. Several anatomical structures are readily detectable with routine fetal MRI sequences; thus, if these landmarks are not delineable, it should raise the suspicion of a pathology. Recommendations regarding favorable sequences/planes are provided. (orig.)
Newborn hearing screening with transient evoked otoacoustic emissions and automatic auditory brainstem response

OpenAIRE

Renata Mota Mamede de Carvallo; Carla Gentile Matas; Isabela de Souza Jardim

2008-01-01

Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU), as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem...
Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

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Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.
Enterovirus 71 Brainstem Encephalitis and Cognitive and Motor Deficits

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J Gordon Millichap

2006-12-01

Full Text Available Follow-up studies were conducted in 63 previously healthy children with enterovirus 71 brainstem encephalitis (49 stage II, 7 stage Ilia, and 7 stage Illb at National Cheng Kung University Hospital, Tainan, Taiwan.
[Forensic application of brainstem auditory evoked potential in patients with brain concussion].

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Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin

2008-12-01

To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (Pconcussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.
Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

Science.gov (United States)

Vuckovich, Joseph A.; Semel, Mara E.; Baxter, Mark G.

2004-01-01

A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…
Regulatory interactions of stress and reward on rat forebrain opioidergic and GABAergic circuitry.

Science.gov (United States)

Christiansen, A M; Herman, J P; Ulrich-Lai, Y M

2011-03-01

Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both reward and stress regulation, suggesting that these systems are prime candidates for mediating stress relief by palatable foods. Thus, the present study (1) determines how palatable ?comfort? food alters stress-induced changes in the mRNA expression of inhibitory neurotransmitters in reward and stress neurocircuitry and (2) identifies candidate brain regions that may underlie comfort food-mediated stress reduction. We used a model of palatable ?snacking? in combination with a model of chronic variable stress followed by in situ hybridization to determine forebrain levels of pro-opioid and glutamic acid decarboxylase (GAD) mRNA. The data identify regions within the extended amygdala, striatum, and hypothalamus as potential regions for mediating hypothalamic-pituitary-adrenal axis buffering following palatable snacking. Specifically, palatable snacking alone decreased pro-enkephalin-A (ENK) mRNA expression in the anterior bed nucleus of the stria terminalis (BST) and the nucleus accumbens, and decreased GAD65 mRNA in the posterior BST. Chronic stress alone increased ENK mRNA in the hypothalamus, nucleus accumbens, amygdala, and hippocampus; increased dynorphin mRNA in the nucleus accumbens; increased GAD65 mRNA in the anterior hypothalamus and BST; and decreased GAD65 mRNA in the dorsal hypothalamus. Importantly, palatable food intake prevented stress-induced gene expression changes in subregions of the hypothalamus, BST, and nucleus accumbens. Overall, these data suggest that complex interactions exist between brain reward and stress pathways and that palatable snacking can
Four cases with localized brain-stem lesion on CT scan following closed head injury

International Nuclear Information System (INIS)

Saeki, Naokatsu; Odaki, Masaru; Oka, Nobuo; Takase, Manabu; Ono, Junichi.

1981-01-01

Cases of primary brain-stem injury following closed head injury, verified by a CT scan, have been increasingly reported. However, most of them have other intracranial lesions in addition to the brain stem, resulting in a poor outcome. The CT scan of 200 cases with severe head injury-Araki's classification of types 3 and 4 - were analysed. Four cases out of them had localized brain-stem lesion without any other significant intracranial injury on a CT scan at the acute stage and had a better outcome than had previously been reported. In this analysis, these 4 cases were studied, and the CT findings, prognosis, and pathogenesis of the localized brain-stem injury were discussed. Follow-up CT of three cases, and taken one month or more later, showed diffuse cortical atrophy. This may indicate the presence of diffuse cerebral injury which could not be seen on CT scans at the acute stage. This atrophic change may also be related with the mechanism of posttraumatic conscious impairment and posttraumatic neurological deficits, such as mental symptoms and impairment of the higher cortical function. Shearing injury is a probable pathogenesis for this diffuse cortical injury. On the other hand, one case did not have any cortical atrophy on a follow-up CT scan. Therefore, this is a case with a localized primary brain-stem injury. Coup injury against the brain stem by a tentorial margin in a case with a small tentorial opening is a possible mechanism producing the localized brain-stem injury. (J.P.N.)
Speech Evoked Auditory Brainstem Response in Stuttering

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Ali Akbar Tahaei

2014-01-01

Full Text Available Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency.
Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.

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Judson, Matthew C; Bergman, Mica Y; Campbell, Daniel B; Eagleson, Kathie L; Levitt, Pat

2009-04-10

The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior. (c) 2009 Wiley-Liss, Inc.
Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

Science.gov (United States)

Wang, Jun Yi; Ngo, Michael M; Hessl, David; Hagerman, Randi J; Rivera, Susan M

2016-01-01

Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation) to 0.978 (for SegAdapter-corrected segmentation) for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large-scale neuroimaging studies, and potentially for segmenting other neural regions as
Neonatal neurological disorders involving the brainstem: neurosonographic approaches through the squamous suture and the foramen magnum

International Nuclear Information System (INIS)

Tu, Yi-Fang; Chen, Cheng-Yu; Lin, Yuh-Jey; Chang, Ying-Chao; Huang, Chao-Ching

2005-01-01

Brainstem damage which often indicates a critical condition is usually underestimated by trans-anterior-fontanel neurosonography (NS) owing to the far-field limitations. Instead, NS alternately scanning through the squamous suture of the temporal bones and the foramen magnum could provide a better visualization of the brainstem structures. The NS characteristics of brainstem lesions caused by various neonatal neurological disorders, such as hypoxic-ischemic encephalopathy (HIE), metabolic encephalopathy, birth trauma and bacterial meningoencephalitis, can be depicted at the acute stage. An echogenic change in the midbrain was found in patients with HIE or metabolic encephalopathy. In addition to the echogenic change, bilateral transtentorial temporal lobe herniation distorting the contour of the midbrain was observed in a patient with group B streptococcus meningoencephalitis, whereas echogenic changes at the level of the pons and/or the medulla oblongata, mainly localized in the dorsal part, could be observed in newborns with severe HIE, maple syrup urine disease or birth trauma. In this pictorial assay, we demonstrate the feasibility of NS imaging in evaluating the entire brainstem structure of critically ill neonates in the near field and illustrate the characteristic features of brainstem involvement in various neonatal neurological disorders along with computed tomography or magnetic resonance imaging correlation. (orig.)
Neonatal neurological disorders involving the brainstem: neurosonographic approaches through the squamous suture and the foramen magnum

Energy Technology Data Exchange (ETDEWEB)

Tu, Yi-Fang [National Cheng Kung University Hospital, Department of Emergency Medicine, Tainan (Taiwan); Chen, Cheng-Yu [National Defense Medical Center, Department of Radiology, Taipei (Taiwan); Lin, Yuh-Jey [National Cheng Kung University Hospital, Department of Pediatrics, Tainan (Taiwan); Chang, Ying-Chao [Kaohsiung Chang Gung Children Hospital, Department of Pediatrics, Kaohsiung (Taiwan); Huang, Chao-Ching [National Cheng Kung University Hospital, Department of Pediatrics, Tainan (Taiwan); National Cheng Kung University Hospital, Department of Institute of Molecular Medicine, Tainan (Taiwan)

2005-09-01

Brainstem damage which often indicates a critical condition is usually underestimated by trans-anterior-fontanel neurosonography (NS) owing to the far-field limitations. Instead, NS alternately scanning through the squamous suture of the temporal bones and the foramen magnum could provide a better visualization of the brainstem structures. The NS characteristics of brainstem lesions caused by various neonatal neurological disorders, such as hypoxic-ischemic encephalopathy (HIE), metabolic encephalopathy, birth trauma and bacterial meningoencephalitis, can be depicted at the acute stage. An echogenic change in the midbrain was found in patients with HIE or metabolic encephalopathy. In addition to the echogenic change, bilateral transtentorial temporal lobe herniation distorting the contour of the midbrain was observed in a patient with group B streptococcus meningoencephalitis, whereas echogenic changes at the level of the pons and/or the medulla oblongata, mainly localized in the dorsal part, could be observed in newborns with severe HIE, maple syrup urine disease or birth trauma. In this pictorial assay, we demonstrate the feasibility of NS imaging in evaluating the entire brainstem structure of critically ill neonates in the near field and illustrate the characteristic features of brainstem involvement in various neonatal neurological disorders along with computed tomography or magnetic resonance imaging correlation. (orig.)

Brainstem pathology in spasmodic dysphonia

Science.gov (United States)

Simonyan, Kristina; Ludlow, Christy L.; Vortmeyer, Alexander O.

2009-01-01

Spasmodic dysphonia (SD) is a primary focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speech production. We examined two rare cases of postmortem brainstem tissue from SD patients compared to four controls. In SD patients, small clusters of inflammation were found in the reticular formation surrounding solitary tract, spinal trigeminal and ambigual nuclei, inferior olive and pyramids. Mild neuronal degeneration and depigmentation were observed in the substantia nigra and locus coeruleus. No abnormal protein accumulations and no demyelination or axonal degeneration were found. These neuropathological findings may provide insights into the pathophysiology of SD. PMID:19795469
Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

International Nuclear Information System (INIS)

Ray, Anamika; Liu Jing; Ayoubi, Patricia; Pope, Carey

2010-01-01

Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2 mg/kg) gene expression profiles and changes in cell signaling pathways 24 h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0 mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis (registered) . Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2 mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2 mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2 mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2 mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse
Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice

DEFF Research Database (Denmark)

Persson, Karin; Rekling, Jens C

2011-01-01

The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem...... and in the facial nucleus. In Fluo-8AM loaded brainstem-spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial...... synchrony with respiratory nerve bursts. In brainstem-spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity...
Identification of clinical target areas in the brainstem of prion‐infected mice

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Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

2015-01-01

Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251
The absence of later wave components in auditory brainstem responses as an initial manifestation of type 2 Gaucher disease.

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Okubo, Yusuke; Goto, Masahiro; Sakakibara, Hiroshi; Terakawa, Toshiro; Kaneko, Takashi; Miyama, Sahoko

2014-12-01

Type 2 Gaucher disease is the most severe neuronopathic form of Gaucher disease and is characterized by severe neurodegeneration with brainstem involvement and organ failure. Prediction or diagnosis of type 2 Gaucher disease before the development of neurological complications is difficult. A 5-month-old female infant presented with deafness without other neurological abnormalities. Auditory brainstem response analysis revealed the absence of later wave components. Two months later, muscular rigidity became evident, followed by the development of opisthotonus and strabismus. Rapid progression of splenomegaly led to the diagnosis of type 2 Gaucher disease. Abnormal auditory brainstem response findings may already exist before the development of severe brainstem abnormalities such as muscular rigidity and opisthotonus in type 2 Gaucher disease. When patients present with deafness and absent later wave components on auditory brainstem response, type 2 Gaucher disease should be included in the differential diagnosis even in the absence of other neurological abnormalities. Copyright © 2014 Elsevier Inc. All rights reserved.
1H magnetic resonance spectroscopy metabolite profiles of neonatal rat hippocampus and brainstem regions following early postnatal exposure to intermittent hypoxia

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Darnall, Robert A.; Chen, Xi; Nemani, Krishnamurthy V.; Sirieix, Chrystelle M.; Gimi, Barjor

2017-03-01

Most premature infants born at less than 30 weeks gestation are exposed to periods of mild intermittent hypoxia (IH) associated with apnea of prematurity and periodic breathing. In adults, IH associated with sleep apnea causes neurochemical and structural alterations in the brain. However, it is unknown whether IH in the premature infant leads to neurodevelopmental impairment. Quantification of biochemical markers that can precisely identify infants at risk of adverse neurodevelopmental outcome is essential. In vivo 1H magnetic resonance spectroscopy (1H MRS) facilitates the quantification of metabolites from distinct regions of the developing brain. We report the changes in metabolite profiles in the brainstem and hippocampal regions of developing rat brains, resulting from exposure to IH. Rat pups were chosen for study because there is rapid postnatal hippocampal development that occurs during the first 4 weeks in the developing rat brain, which corresponds to the first 2-3 postnatal years of development in humans. The brainstem was examined because of our interest in respiratory control disorders in the newborn and because of brainstem gliosis described in infants who succumb to Sudden Infant Death Syndrome (SIDS). Metabolite profiles were compared between hypoxia treated rat pups (n = 9) and normoxic controls (n = 6). Metabolite profiles were acquired using the Point-RESolved spectroscopy (PRESS) MRS sequence and were quantified using the TARQUIN software. There was a significant difference in the concentrations of creatine (p = 0.031), total creatine (creatine + phosphocreatine) (p = 0.028), and total choline (p = 0.001) in the brainstem, and glycine (p = 0.031) in the hippocampal region. The changes are consistent with altered cellular bioenergetics and metabolism associated with hypoxic insult.
Topographic Organization of Cholinergic Innervation From the Basal Forebrain to the Visual Cortex in the Rat

Directory of Open Access Journals (Sweden)

Frédéric Huppé-Gourgues

2018-03-01

Full Text Available Acetylcholine is an important neurotransmitter for the regulation of visual attention, plasticity, and perceptual learning. It is released in the visual cortex predominantly by cholinergic projections from the basal forebrain, where stimulation may produce potentiation of visual processes. However, little is known about the fine organization of these corticopetal projections, such as whether basal forebrain neurons projecting to the primary and secondary visual cortical areas (V1 and V2, respectively are organized retinotopically. The aim of this study was to map these basal forebrain-V1/V2 projections. Microinjections of the fluorescent retrograde tracer cholera toxin b fragment in different sites within V1 and V2 in Long–Evans rats were performed. Retrogradely labeled cell bodies in the horizontal and vertical limbs of the diagonal band of Broca (HDB and VDB, respectively, nucleus basalis magnocellularis, and substantia innominata (SI, were mapped ex vivo with a computer-assisted microscope stage controlled by stereological software. Choline acetyltranferase immunohistochemistry was used to identify cholinergic cells. Our results showed a predominance of cholinergic projections coming from the HDB. These projections were not retinotopically organized but projections to V1 arised from neurons located in the anterior HDB/SI whereas projections to V2 arised from neurons located throughout the whole extent of HDB/SI. The absence of a clear topography of these projections suggests that BF activation can stimulate visual cortices broadly.
Imaging of adult brainstem gliomas

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Purohit, Bela, E-mail: purohitbela@yahoo.co.in; Kamli, Ali A.; Kollias, Spyros S.

2015-04-15

Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.
Neuropeptide Y in the forebrain of the adult male cichlid fish Oreochromis mossambicus: distribution, effects of castration and testosterone replacement.

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Sakharkar, Amul J; Singru, Praful S; Sarkar, Koustav; Subhedar, Nishikant K

2005-08-22

We studied the organization of the neuropeptide Y (NPY)-immunoreactive system in the forebrain of adult male cichlid fish Oreochromis mossambicus and its response to castration and testosterone replacement by using morphometric methods. Immunoreactivity for NPY was widely distributed in the forebrain, and the pattern generally resembled that in other teleosts. Whereas immunoreactivity was conspicuous in the ganglia of nervus terminalis (NT; or nucleus olfactoretinalis), a weak reaction was detected in some granule cells in the olfactory bulb and in the cells of area ventralis telencephali pars lateralis (Vl). Moderately to intensely immunoreactive cells were distinctly seen in the nucleus entopeduncularis (NE), nucleus preopticus (NPO), nucleus lateralis tuberis (NLT), paraventricular organ (PVO), and midbrain tegmentum (MT). NPY fibers were widely distributed in the forebrain. Castration for 10/15 days resulted in a drastic loss of immunoreactivity in the cells of NE (P<0.001) and a significant decrease (P<0.01) in their cell nuclear size. However, cell nuclei of the NT neurons showed a significant increase in size. A highly significant reduction in the NPY-immunoreactive fiber density (P<0.001) was observed in several areas of the forebrain. Although testosterone replacement reversed these changes, fibers in some areas showed supranormal responses. Immunoreactive cells in Vl, NPO, NLT, PVO, and MT and fiber density in some other areas did not respond to castration. We suggest that the NPY-immunoreactive elements that respond to castration and testosterone replacement may serve as the substrate for processing the positive feedback action of the steroid hormone. (c) 2005 Wiley-Liss, Inc.
Increases in extracellular serotonin and dopamine metabolite levels in the basal forebrain during sleep deprivation

NARCIS (Netherlands)

Zant, J.C.; Leenaars, C.H.; Kostin, A.; van Someren, E.J.W.; Porrka-Heiskanen, T.

2011-01-01

The basal forebrain (BF) is an important mediator of cortical arousal, which is innervated by all ascending arousal systems. During sleep deprivation (SD) a site-specific accumulation of sleep factors in the BF results in increased sleep pressure (Kalinchuk et al., 2006; Porkka-Heiskanen et al.,
Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats.

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Baxter, Mark G; Bucci, David J; Gorman, Linda K; Wiley, Ronald G; Gallagher, Michela

2013-10-01

Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory. 2013 APA, all rights reserved
Comprehensive evaluation of a child with an auditory brainstem implant.

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Eisenberg, Laurie S; Johnson, Karen C; Martinez, Amy S; DesJardin, Jean L; Stika, Carren J; Dzubak, Danielle; Mahalak, Mandy Lutz; Rector, Emily P

2008-02-01

We had an opportunity to evaluate an American child whose family traveled to Italy to receive an auditory brainstem implant (ABI). The goal of this evaluation was to obtain insight into possible benefits derived from the ABI and to begin developing assessment protocols for pediatric clinical trials. Case study. Tertiary referral center. Pediatric ABI Patient 1 was born with auditory nerve agenesis. Auditory brainstem implant surgery was performed in December, 2005, in Verona, Italy. The child was assessed at the House Ear Institute, Los Angeles, in July 2006 at the age of 3 years 11 months. Follow-up assessment has continued at the HEAR Center in Birmingham, Alabama. Auditory brainstem implant. Performance was assessed for the domains of audition, speech and language, intelligence and behavior, quality of life, and parental factors. Patient 1 demonstrated detection of sound, speech pattern perception with visual cues, and inconsistent auditory-only vowel discrimination. Language age with signs was approximately 2 years, and vocalizations were increasing. Of normal intelligence, he exhibited attention deficits with difficulty completing structured tasks. Twelve months later, this child was able to identify speech patterns consistently; closed-set word identification was emerging. These results were within the range of performance for a small sample of similarly aged pediatric cochlear implant users. Pediatric ABI assessment with a group of well-selected children is needed to examine risk versus benefit in this population and to analyze whether open-set speech recognition is achievable.
Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura

DEFF Research Database (Denmark)

Hougaard, Anders; Amin, Faisal M; Christensen, Casper E

2017-01-01

symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering...... of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas......-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability...
A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia.

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Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn; Munir, Jared; Chandler-Militello, Devin; Wang, Su; Goldman, Steven A

2014-11-26

Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative proportion of mouse GPCs fell as a function of time, concomitant with the mitotic expansion and spread of donor hGPCs. By a year after neonatal xenograft, the forebrain GPC populations of implanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo. Copyright © 2014 the authors 0270-6474/14/3416153-09$15.00/0.
Neuroregulatory and neuroendocrine GnRH pathways in the hypothalamus and forebrain of the baboon.

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Marshall, P E; Goldsmith, P C

1980-07-14

The distribution of neurons containing gonadotropin-releasing hormone (GnRH) in the baboon hypothalamus and forebrain was studied immunocytochemically by light and electron microscopy. GnRH was present in the perikarya, axonal and dendritic processes of immunoreactive neurons. Three populations of GnRH neurons could be distinguished. Most of the GnRH neurons which are assumed to directly influence the anterior pituitary were in the medial basal hypothalamus. Other cells that projected to the median eminence were found scattered throughout the hypothalamus. A second, larger population of neurons apparently was not involved with control of the anterior pituitary. These neurons were generally found within afferent and efferent pathways of the hypothalamus and forebrain, and may receive external information affecting reproduction. A few neurons projecting to the median eminence were also observed sending collaterals to other brain areas. Thus, in addition to their neuroendocrine role, these cells possibly have neuroregulatory functions. The inference is made that these bifunctional neurons, together with the widely observed GnRH-GnRH cellular interactions may help to synchronize ovulation and sexual behavior.
Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

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Jun Yi Wang

Full Text Available Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation to 0.978 (for SegAdapter-corrected segmentation for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large
The role of the auditory brainstem in processing musically-relevant pitch

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Gavin M. Bidelman

2013-05-01

Full Text Available Neuroimaging work has shed light on the cerebral architecture involved in processing the melodic and harmonic aspects of music. Here, recent evidence is reviewed illustrating that subcortical auditory structures contribute to the early formation and processing of musically-relevant pitch. Electrophysiological recordings from the human brainstem and population responses from the auditory nerve reveal that nascent features of tonal music (e.g., consonance/dissonance, pitch salience, harmonic sonority are evident at early, subcortical levels of the auditory pathway. The salience and harmonicity of brainstem activity is strongly correlated with listeners’ perceptual preferences and perceived consonance for the tonal relationships of music. Moreover, the hierarchical ordering of pitch intervals/chords described by the Western music practice and their perceptual consonance is well-predicted by the salience with which pitch combinations are encoded in subcortical auditory structures. While the neural correlates of consonance can be tuned and exaggerated with musical training, they persist even in the absence of musicianship or long-term enculturation. As such, it is posited that the structural foundations of musical pitch might result from innate processing performed by the central auditory system. A neurobiological predisposition for consonant, pleasant sounding pitch relationships may be one reason why these pitch combinations have been favored by composers and listeners for centuries. It is suggested that important perceptual dimensions of music emerge well before the auditory signal reaches cerebral cortex and prior to attentional engagement. While cortical mechanisms are no doubt critical to the perception, production, and enjoyment of music, the contribution of subcortical structures implicates a more integrated, hierarchically organized network underlying music processing within the brain.
Brainstem response audiometry in the determination of low-frequency hearing loss : a study of various methods for frequency-specific ABR-threshold assessment

NARCIS (Netherlands)

E.A.G.J. Conijn

1992-01-01

textabstractBrainstem Electric Response Audiometry (BERA) is a method to visualize some of the electric activity generated in the auditory nerve and the brainstem during the processing of sound. The amplitude of the Auditory Brainstem Response (ABR) is very small (0.05-0.5 flV). The potentials
Lung inflammation induces IL-1β expression in hypoglossal neurons in rat brainstem

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Jafri, Anjum; Belkadi, Abdelmadjid; Zaidi, Syed I. A.; Getsy, Paulina; Wilson, Christopher G.; Martin, Richard J.

2013-01-01

Perinatal inflammation is associated with respiratory morbidity. Immune modulation of brainstem respiratory control centers may provide a link for this pathobiology. We exposed 11-day old rats to intratracheal lipopolysaccharide (LPS, 0.5 µg/g) to test the hypothesis that intrapulmonary inflammation increases expression of the proinflammatory cytokine IL-1β within respiratory-related brainstem regions. Intratracheal LPS resulted in a 32% increase in IL-1β protein expression in the medulla oblongata. In situ hybridization showed increased intensity of IL-1β mRNA but no change in neuronal numbers. Co-localization experiments showed that hypoglossal neurons express IL-1β mRNA and immunostaining showed a 43% increase in IL-1β protein-expressing cells after LPS exposure. LPS treatment also significantly increased microglial cell numbers though they did not express IL-1β mRNA. LPS-induced brainstem expression of neuronal IL-1β mRNA and protein may have implications for our understanding of the vulnerability of neonatal respiratory control in response to a peripheral pro-inflammatory stimulus. PMID:23648475
Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

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Ellis, C M; Simmons, A; Lemmens, G; Williams, S C; Parkes, J D

1998-02-01

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

Science.gov (United States)

Daulatzai, Mak Adam

2016-10-01

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.
Normal development of brainstem in childhood. Measurement of the area on mid-sagittal MR imaging

Energy Technology Data Exchange (ETDEWEB)

Kutomi, Kimiko [Teikyo Univ., Tokyo (Japan). Faculty of Medicine

2005-05-01

Developmental abnormality of brainstem is shown in pediatric patients with mental retardation, autism, periventricular leukomalacia, neurodegenerative disease, and so on. Our purpose here is to clarify the normal developmental pattern of the brainstem. We measured the area of tectum, midbrain tegmentum, pons, basis pontis and pontine tegmentum on mid-sagittal MR images in 111 children (newborn to 20 year old). Different growth patterns were shown in all parts of the brainstem. Tectum showed a subtle increase in area from the newborn to adult period, while midbrain tegmentum and pontine tegmenturn showed a mild and gradual increase in area. Pons and pontine tegmentum showed a rapid and prominent increase in area from newborn to infant period and gradual increase in area until the adult period. These different growth patterns seemed to be consistent with differences in the myelination cycles of the neuronal fibers, maturation of the nuclei and proliferation of glial cells in each part of the brainstem. Mid-sagittal MR imaging of the head is accurate and reproducible and is used conveniently in routine head MR study, making it very useful for the diagnosis of many central nervous diseases and anomalies. We believe that this new milestone provided in this study will be helpful in distinguishing normal children from those that have neurodegenerative disorders. (author)
Normal development of brainstem in childhood. Measurement of the area on mid-sagittal MR imaging

International Nuclear Information System (INIS)

Kutomi, Kimiko

2005-01-01

Developmental abnormality of brainstem is shown in pediatric patients with mental retardation, autism, periventricular leukomalacia, neurodegenerative disease, and so on. Our purpose here is to clarify the normal developmental pattern of the brainstem. We measured the area of tectum, midbrain tegmentum, pons, basis pontis and pontine tegmentum on mid-sagittal MR images in 111 children (newborn to 20 year old). Different growth patterns were shown in all parts of the brainstem. Tectum showed a subtle increase in area from the newborn to adult period, while midbrain tegmentum and pontine tegmenturn showed a mild and gradual increase in area. Pons and pontine tegmentum showed a rapid and prominent increase in area from newborn to infant period and gradual increase in area until the adult period. These different growth patterns seemed to be consistent with differences in the myelination cycles of the neuronal fibers, maturation of the nuclei and proliferation of glial cells in each part of the brainstem. Mid-sagittal MR imaging of the head is accurate and reproducible and is used conveniently in routine head MR study, making it very useful for the diagnosis of many central nervous diseases and anomalies. We believe that this new milestone provided in this study will be helpful in distinguishing normal children from those that have neurodegenerative disorders. (author)
Regional glucose utilization and blood flow following graded forebrain ischemia in the rat: correlation with neuropathology

International Nuclear Information System (INIS)

Ginsberg, M.D.; Graham, D.I.; Busto, R.

1985-01-01

Regional patterns of cerebral glucose utilization (rCMRglc) and blood flow (rCBF) were examined in the early recovery period following transient forebrain ischemia in order to correlate early postischemic physiological events with regionally selective patterns of ischemic neuropathology. Wistar rats were subjected to 30 or 60 minutes of graded forebrain ischemia by a method combining unilateral occlusion of the common carotid artery with moderate elevation of intracranial pressure and mild hypotension; this procedure results in a high-grade ischemic deficit affecting chiefly the lateral neocortex, striatum, and hippocampus ipsilateral to the carotid occlusion. Simultaneous measurements of rCMRglc and rCBF made in regional tissue samples after 2 and 4 hours of postischemic recirculation using a double-tracer radioisotopic strategy revealed a disproportionately high level of glucose metabolism relative to blood flow in the early postischemic striatum, owing to the resumption of nearly normal rCMRglc in the face of depressed flow. In contrast, the neocortex, which had been equally ischemic, showed parallel depressions of both metabolism and blood flow during early recovery. Light microscopy at 4 and 8 hours after recovery revealed the striatum to be the predominant locus of ischemic neuronal alterations, whereas neocortical lesions were much less prominent in extent and severity at this time. The resumption of normal levels of metabolism in the setting of a disproportionate depression of rCBF in the early postischemic period may accentuate the process of neuronal injury initiated by ischemia and may contribute to the genesis of neuronal necrosis in selectively vulnerable areas of the forebrain
Towards an optimal paradigm for simultaneously recording cortical and brainstem auditory evoked potentials.

Science.gov (United States)

Bidelman, Gavin M

2015-02-15

Simultaneous recording of brainstem and cortical event-related brain potentials (ERPs) may offer a valuable tool for understanding the early neural transcription of behaviorally relevant sounds and the hierarchy of signal processing operating at multiple levels of the auditory system. To date, dual recordings have been challenged by technological and physiological limitations including different optimal parameters necessary to elicit each class of ERP (e.g., differential adaptation/habitation effects and number of trials to obtain adequate response signal-to-noise ratio). We investigated a new stimulus paradigm for concurrent recording of the auditory brainstem frequency-following response (FFR) and cortical ERPs. The paradigm is "optimal" in that it uses a clustered stimulus presentation and variable interstimulus interval (ISI) to (i) achieve the most ideal acquisition parameters for eliciting subcortical and cortical responses, (ii) obtain an adequate number of trials to detect each class of response, and (iii) minimize neural adaptation/habituation effects. Comparison between clustered and traditional (fixed, slow ISI) stimulus paradigms revealed minimal change in amplitude or latencies of either the brainstem FFR or cortical ERP. The clustered paradigm offered over a 3× increase in recording efficiency compared to conventional (fixed ISI presentation) and thus, a more rapid protocol for obtaining dual brainstem-cortical recordings in individual listeners. We infer that faster recording of subcortical and cortical potentials might allow more complete and sensitive testing of neurophysiological function and aid in the differential assessment of auditory function. Copyright © 2014 Elsevier B.V. All rights reserved.
Novel Anterior Brainstem Magnetic Resonance Imaging Findings in Non-Small Cell Lung Cancer with Leptomeningeal Carcinomatosis

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Chun-Yu Cheng

2017-10-01

Full Text Available Leptomeningeal carcinomatosis (LC is found in around 4% of patients with non-small cell lung cancer (NSCLC. The most common radiological finding of LC is diffuse leptomeningeal enhancement on contrast-enhanced brain magnetic resonance imaging (MRI. Herein, we report a novel brain MRI finding—non-enhanced, band-like, symmetric restricted diffusion along the anterior surface of the brainstem—of LC in four patients with NSCLC. We also identified three additional cases with similar MRI findings in a literature review. We hypothesized that the restricted diffusion along the anterior brainstem was caused by malignant cells concentrating in the cistern around the brainstem and infiltrating into the circumferential perforating arteries along the anterior brainstem surface, which then resulted in microinfarctions.
Lack of cross-tolerance between haloperidol and clozapine towards Fos-protein induction in rat forebrain regions

NARCIS (Netherlands)

Sebens, JB; Koch, T; Korf, J

1996-01-01

We investigated whether the acute effects of haloperidol and clozapine on Fos expression in the rat forebrain are mediated by the same receptors through evaluation of cross-tolerance, particularly in the commonly affected areas. Acutely administered haloperidol (1 mg/kg, i.p.) and clozapine (20
The effect of high mesencephalic transection (cerveau isolé) and pentobarbital on basal forebrain mechanisms of EEG synchronization.

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Obál, F; Benedek, G; Szikszay, M; Obál, F

1979-01-01

A study was made of the effects of high mesencephalic transection (cerveau isolé) and low doses of pentobarbital on the cortical synchronizations elicited in acute immobilized cats by (a) low frequency stimulation of the lateral hypothalamus (HL) and nucleus ventralis anterior thalami (VA) and (b) by low and high frequency stimulation of the laterobasal preoptic region (RPO) and olfactory tubercle (TbOf). The results obtained were as follows: (1) The synchronizations induced by basal forebrain stimulations were found to survive in acute cerveau isolé cats, moreover, even a facilitation of the synchronizing effect were observed. (2) A gradual facilitation was observed upon TbOf and RPO stimulation, while in the case of VA and HL stimulations, the facilitation appeared immediately after the transection. (3) Low doses of pentobarbital depressed the cortical effects of TbOf stimulation, while an increase of the synchronizing effect of low frequency VA and HL stimulation was found. The observations suggested that (i) the synchronizing mechanism in the ventral part of the basal forebrain (RPO and TbOf) differs from that of the thalamus and HL; (ii) the basal forebrain synchronizing mechanism is effective without the contribution of the brain stem; (iii) the mechanism responsible for the synchronizing effect of low frequency HL stimulation is similar as that described for the thalamus.
Optimal technique of linear accelerator–based stereotactic radiosurgery for tumors adjacent to brainstem

International Nuclear Information System (INIS)

Chang, Chiou-Shiung; Hwang, Jing-Min; Tai, Po-An; Chang, You-Kang; Wang, Yu-Nong; Shih, Rompin; Chuang, Keh-Shih

2016-01-01

Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)–based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5 different lesion catalogs were collected, and the patients were divided into 2 distance groups—1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5 cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1 cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2 cm 3 to 21.9 cm 3 . Regarding the dose homogeneity index (HI ICRU ) and conformity index (CI ICRU ) were without significant difference between techniques statistically. However, the average CI ICRU = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V 4 Gy of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V 2 Gy of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better
Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor.

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Oh, J D; Butcher, L L; Woolf, N J

1991-04-24

Hyperthyroidism, induced in rat pups by the daily intraperitoneal administration of 1 microgram/g body weight triiodothyronine, facilitated the development of ChAT fiber plexuses in brain regions innervated by basal forebrain cholinergic neurons, leading to an earlier and increased expression of cholinergic markers in those fibers in the cortex, hippocampus and amygdala. A similar enhancement was seen in the caudate-putamen complex. This histochemical profile was correlated with an accelerated appearance of ChAT-positive telencephalic puncta, as well as with a larger total number of cholinergic terminals expressed, which persisted throughout the eight postnatal week, the longest time examined in the present study. Hypothyroidism was produced in rat pups by adding 0.5% propylthiouracil to the dams' diet beginning the day after birth. This dietary manipulation resulted in the diminished expression of ChAT in forebrain fibers and terminals. Hypothyroid treatment also reduced the quantity of ChAT puncta present during postnatal weeks 2 and 3, and, from week 4 and continuing through week 6, the number of ChAT-positive terminals in the telencephalic regions examined was actually less than the amount extant during the former developmental epoch. Immunostaining for nerve growth factor receptor (NGF-R), which is associated almost exclusively with ChAT-positive somata and fibers in the basal forebrain, demonstrated a different time course of postnatal development. Forebrain fibers and terminals demonstrating NGF-R were maximally visualized 1 week postnatally, a time at which these same neuronal elements evinced minimal ChAT-like immunopositivity. Thereafter and correlated with increased immunoreactivity for ChAT, fine details of NGF-R stained fibers were observed less frequently. Although propylthiouracil administration decreased NGF-R immunodensity, no alteration in the development of that receptor was observed as a function of triiodothyronine treatment. Cholinergic
Effect of Infant Prematurity on Auditory Brainstem Response at Preschool Age

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Sara Hasani

2013-03-01

Full Text Available Introduction: Preterm birth is a risk factor for a number of conditions that requires comprehensive examination. Our study was designed to investigate the impact of preterm birth on the processing of auditory stimuli and brain structures at the brainstem level at a preschool age. Materials and Methods: An auditory brainstem response (ABR test was performed with low rates of stimuli in 60 children aged 4 to 6 years. Thirty subjects had been born following a very preterm labor or late-preterm labor and 30 control subjects had been born following a full-term labor. Results: Significant differences in the ABR test result were observed in terms of the inter-peak intervals of the I–III and III–V waves, and the absolute latency of the III wave (P
Macrovascular Decompression of the Brainstem and Cranial Nerves: Evolution of an Anteromedial Vertebrobasilar Artery Transposition Technique.

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Choudhri, Omar; Connolly, Ian D; Lawton, Michael T

2017-08-01

Tortuous and dolichoectatic vertebrobasilar arteries can impinge on the brainstem and cranial nerves to cause compression syndromes. Transposition techniques are often required to decompress the brainstem with dolichoectatic pathology. We describe our evolution of an anteromedial transposition technique and its efficacy in decompressing the brainstem and relieving symptoms. To present the anteromedial vertebrobasilar artery transposition technique for macrovascular decompression of the brainstem and cranial nerves. All patients who underwent vertebrobasilar artery transposition were identified from the prospectively maintained database of the Vascular Neurosurgery service, and their medical records were reviewed retrospectively. The extent of arterial displacement was measured pre- and postoperatively on imaging. Vertebrobasilar arterial transposition and macrovascular decompression was performed in 12 patients. Evolution in technique was characterized by gradual preference for the far-lateral approach, use of a sling technique with muslin wrap, and an anteromedial direction of pull on the vertebrobasilar artery with clip-assisted tethering to the clival dura. With this technique, mean lateral displacement decreased from 6.6 mm in the first half of the series to 3.8 mm in the last half of the series, and mean anterior displacement increased from 0.8 to 2.5 mm, with corresponding increases in satisfaction and relief of symptoms. Compressive dolichoectatic pathology directed laterally into cranial nerves and posteriorly into the brainstem can be corrected with anteromedial transposition towards the clivus. Our technique accomplishes this anteromedial transposition from an inferolateral surgical approach through the vagoaccessory triangle, with sling fixation to clival dura using aneurysm clips. Copyright © 2017 by the Congress of Neurological Surgeons
Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area – an anterograde tract-tracing study

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Rege Sugárka Papp

2014-05-01

Full Text Available The projections from the dorsolateral hypothalamic area (DLH to the lower brainstem have been investigated by using biotinylated dextran amine (BDA, an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area, and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribution patterns of BDA-positive fibers were mapped on serial sections between the hypothalamus and spinal cord in 22 rats. BDA-labeled fibers were observable over 100 different brainstem areas, nuclei or subdivisions. Injections into the 8 DLH subdivisions established distinct topographical patterns. In general, the density of labeled fibers was low in the lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the lateral and ventrolateral parts of the periaqueductal gray, the Barrington’s and the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in the lower brainstem (9 noradrenaline, 3 adrenaline and 9 serotonin cell groups received labeled fibers, some of them from all, or at least 7 DLH subdivisions, mainly from perifornical and ventral lateral hypothalamic neurons. Some of the tegmental nuclei and nuclei of the reticular formation were widely innervated, although the density of the BDA-labeled fibers was generally low. No definitive descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were seen in the lower brainstem. These descending fibers joined some of the large tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive fibers of DLH origin throughout the lower brainstem was comparable to patterns of previously published orexin- or melanin-concentrating hormone-immunoreactive fibers with somewhat differences.
Cavernous sinus thrombosis syndrome and brainstem involvement in patient with leptospirosis: Two rare complications of leptospirosis

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Shahriyar Alian

2014-01-01

Full Text Available Leptospirosis is a bacterial disease that is caused by pathogenic spirochetes of the genus Leptospira. It can affect humans and animals. In humans, it can lead to a wide spectrum of symptoms. It is known as the most common zoonosis in the world. The typical presentation of the disease is an acute biphasic febrile illness with or without jaundice. Less common clinical manifestations may result from involvement of different human body systems. In many places, this disease may be under-diagnosed, especially when associated with neurological complications. Moreover, without treatment, leptospirosis can lead to organ damages, and even death. Neurological complications are uncommon and are reported in a few cases. Cavernous sinus thrombosis syndrome and brainstem involvement are rare complications of leptospirosis and are associated with a high mortality risk. To our knowledge, no such cases have been reported in the literature.
Impact of monaural frequency compression on binaural fusion at the brainstem level.

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Klauke, Isabelle; Kohl, Manuel C; Hannemann, Ronny; Kornagel, Ulrich; Strauss, Daniel J; Corona-Strauss, Farah I

2015-08-01

A classical objective measure for binaural fusion at the brainstem level is the so-called β-wave of the binaural interaction component (BIC) in the auditory brainstem response (ABR). However, in some cases it appeared that a reliable detection of this component still remains a challenge. In this study, we investigate the wavelet phase synchronization stability (WPSS) of ABR data for the analysis of binaural fusion and compare it to the BIC. In particular, we examine the impact of monaural nonlinear frequency compression on binaural fusion. As the auditory system is tonotopically organized, an interaural frequency mismatch caused by monaural frequency compression could negatively effect binaural fusion. In this study, only few subjects showed a detectable β-wave and in most cases only for low ITDs. However, we present a novel objective measure for binaural fusion that outperforms the current state-of-the-art technique (BIC): the WPSS analysis showed a significant difference between the phase stability of the sum of the monaurally evoked responses and the phase stability of the binaurally evoked ABR. This difference could be an indicator for binaural fusion in the brainstem. Furthermore, we observed that monaural frequency compression could indeed effect binaural fusion, as the WPSS results for this condition vary strongly from the results obtained without frequency compression.
Neurodegenerative changes in the brainstem and olfactory bulb in people older than 50 years old: a descriptive study

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Francine Hehn de Oliveira

2015-07-01

Full Text Available With the increase in life expectancy in Brazil, concerns have grown about the most prevalent diseases in elderly people. Among these diseases are neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Protein deposits related to the development of these diseases can pre-date the symptomatic phases by years. The tau protein is particularly interesting: it might be found in the brainstem and olfactory bulb long before it reaches the limbic cortex, at which point symptoms occur. Of the 14 brains collected in this study, the tau protein was found in the brainstems of 10 (71.42% and in olfactory bulbs of 3 out 11. Of the 7 individuals who had a final diagnosis of Alzheimer’s disease (AD, 6 presented tau deposits in some region of the brainstem. Our data support the idea of the presence of tau protein in the brainstem and olfactory bulb in the earliest stages of AD.
Comparison of sensitivity of magnetic resonance imaging and evoked potentials in the detection of brainstem involvement in multiple sclerosis

International Nuclear Information System (INIS)

Comi, G.; Martinelli, V.; Medaglini, S.; Locatelli, T.; Magnani, G.; Poggi, A.; Triulzi, F.

1988-01-01

A comparison was made of the sensitivity of magnetic resonance imaging and the combined use of Brainstem Auditory Evoked Potential and Median Somatosensory Evoked Potential in the detection of brainstem dysfunction in 54 multiple sclerosis patients. 10 refs.; 2 tabs
Processing Complex Sounds Passing through the Rostral Brainstem: The New Early Filter Model

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Marsh, John E.; Campbell, Tom A.

2016-01-01

The rostral brainstem receives both “bottom-up” input from the ascending auditory system and “top-down” descending corticofugal connections. Speech information passing through the inferior colliculus of elderly listeners reflects the periodicity envelope of a speech syllable. This information arguably also reflects a composite of temporal-fine-structure (TFS) information from the higher frequency vowel harmonics of that repeated syllable. The amplitude of those higher frequency harmonics, bearing even higher frequency TFS information, correlates positively with the word recognition ability of elderly listeners under reverberatory conditions. Also relevant is that working memory capacity (WMC), which is subject to age-related decline, constrains the processing of sounds at the level of the brainstem. Turning to the effects of a visually presented sensory or memory load on auditory processes, there is a load-dependent reduction of that processing, as manifest in the auditory brainstem responses (ABR) evoked by to-be-ignored clicks. Wave V decreases in amplitude with increases in the visually presented memory load. A visually presented sensory load also produces a load-dependent reduction of a slightly different sort: The sensory load of visually presented information limits the disruptive effects of background sound upon working memory performance. A new early filter model is thus advanced whereby systems within the frontal lobe (affected by sensory or memory load) cholinergically influence top-down corticofugal connections. Those corticofugal connections constrain the processing of complex sounds such as speech at the level of the brainstem. Selective attention thereby limits the distracting effects of background sound entering the higher auditory system via the inferior colliculus. Processing TFS in the brainstem relates to perception of speech under adverse conditions. Attentional selectivity is crucial when the signal heard is degraded or masked: e
Shp2 in Forebrain Neurons Regulates Synaptic Plasticity, Locomotion, and Memory Formation in Mice

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Kusakari, Shinya; Saitow, Fumihito; Ago, Yukio; Shibasaki, Koji; Sato-Hashimoto, Miho; Matsuzaki, Yasunori; Kotani, Takenori; Murata, Yoji; Hirai, Hirokazu; Matsuda, Toshio; Suzuki, Hidenori

2015-01-01

Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. In contrast, ablation of Shp2 enhanced high-K+-induced Erk activation in both cultured cortical neurons and synaptosomes, whereas it inhibited that induced by brain-derived growth factor in cultured neurons. Posttetanic potentiation and paired-pulse facilitation were attenuated and enhanced, respectively, in hippocampal slices from Shp2 cKO mice. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. Our data suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation. PMID:25713104
Characterization of muscarinic receptor subtypes in human tissues

International Nuclear Information System (INIS)

Giraldo, E.; Martos, F.; Gomez, A.; Garcia, A.; Vigano, M.A.; Ladinsky, H.; Sanchez de La Cuesta, F.

1988-01-01

The affinities of selective, pirenzepine and AF-DX 116, and classical, N-methylscopolamine and atropine, muscarinic cholinergic receptor antagonists were investigated in displacement binding experiments with [ 3 H]Pirenzepine and [ 3 H]N-methylscopolamine in membranes from human autoptic tissues (forebrain, cerebellum, atria, ventricle and submaxillary salivary glands). Affinity estimates of N-methylscopolamine and atropine indicated a non-selective profile. Pirenzepine showed differentiation between the M 1 neuronal receptor of the forebrain and the receptors in other tissues while AF-DX 116 clearly discriminated between muscarinic receptors of heart and glands. The results in human tissues confirm the previously described selectivity profiles of pirenzepine and AF-DX 116 in rat tissues. These findings thus reveal the presence also in man of three distinct muscarinic receptor subtypes: the neuronal M 1 , the cardiac M 2 and the glandular M 3

Awake craniotomy for assisting placement of auditory brainstem implant in NF2 patients.

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Zhou, Qiangyi; Yang, Zhijun; Wang, Zhenmin; Wang, Bo; Wang, Xingchao; Zhao, Chi; Zhang, Shun; Wu, Tao; Li, Peng; Li, Shiwei; Zhao, Fu; Liu, Pinan

2018-06-01

Auditory brainstem implants (ABIs) may be the only opportunity for patients with NF2 to regain some sense of hearing sensation. However, only a very small number of individuals achieved open-set speech understanding and high sentence scores. Suboptimal placement of the ABI electrode array over the cochlear nucleus may be one of main factors for poor auditory performance. In the current study, we present a method of awake craniotomy to assist with ABI placement. Awake surgery and hearing test via the retrosigmoid approach were performed for vestibular schwannoma resections and auditory brainstem implantations in four patients with NF2. Auditory outcomes and complications were assessed postoperatively. Three of 4 patients who underwent awake craniotomy during ABI surgery received reproducible auditory sensations intraoperatively. Satisfactory numbers of effective electrodes, threshold levels and distinct pitches were achieved in the wake-up hearing test. In addition, relatively few electrodes produced non-auditory percepts. There was no serious complication attributable to the ABI or awake craniotomy. It is safe and well tolerated for neurofibromatosis type 2 (NF2) patients using awake craniotomy during auditory brainstem implantation. This method can potentially improve the localization accuracy of the cochlear nucleus during surgery.
Endovascular treatment of brain-stem arteriovenous malformations: safety and efficacy

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Liu, H.M.; Wang, Y.H.; Chen, Y.F.; Huang, K.M. [Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, 10016, Taipei (Taiwan); Tu, Y.K. [Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, 1001, Taipei (Taiwan)

2003-09-01

Our purpose was to evaluate the safety and efficacy of endovascular treatment of brain-stem arteriovenous malformations (AVMs), reviewing six cases managed in the last 5 years. There were four patients who presented with bleeding, one with a progressive neurological deficit and one with obstructive hydrocephalus. Of the six patients, one showed 100%, one 90%, two 75% and two about 50% angiographic obliteration of the AVM after embolisation; the volume decreased about 75% on average. Five patients had a good outcome and one an acceptable outcome, with a mild postprocedure neurological deficit; none had further bleeding during midterm follow-up. Endovascular management of a brain-stem AVM may be an alternative to treatment such as radiosurgery and microsurgery in selected cases. It may be not as risky as previously thought. Embolisation can reduce the size of the AVM and possibly make it more treatable by radiosurgery and decrease the possibility of radiation injury. (orig.)
Loud Music Exposure and Cochlear Synaptopathy in Young Adults: Isolated Auditory Brainstem Response Effects but No Perceptual Consequences.

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Grose, John H; Buss, Emily; Hall, Joseph W

2017-01-01

The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.
Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration

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McBrayer, Zofeyah L.; Dimova, Jiva; Pisansky, Marc T.; Sun, Mu; Beppu, Hideyuki; Gewirtz, Jonathan C.; O’Connor, Michael B.

2015-01-01

To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not ...
Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice

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Bian Xiling

2011-10-01

Full Text Available Abstract Background Dysfunction of brain-gut interaction is thought to underlie visceral hypersensitivity which causes unexplained abdominal pain syndromes. However, the mechanism by which alteration of brain function in the brain-gut axis influences the perception of visceral pain remains largely elusive. In this study we investigated whether altered brain activity can generate visceral hyperalgesia. Results Using a forebrain specific αCaMKII promoter, we established a line of transgenic (Tg mice expressing a dominant-negative pore mutant of the Kv7.2/KCNQ2 channel which suppresses native KCNQ/M-current and enhances forebrain neuronal excitability. Brain slice recording of hippocampal pyramidal neurons from these Tg mice confirmed the presence of hyperexcitable properties with increased firing. Behavioral evaluation of Tg mice exhibited increased sensitivity to visceral pain induced by intraperitoneal (i.p. injection of either acetic acid or magnesium sulfate, and intracolon capsaicin stimulation, but not cutaneous sensation for thermal or inflammatory pain. Immunohistological staining showed increased c-Fos expression in the somatosensory SII cortex and insular cortex of Tg mice that were injected intraperitoneally with acetic acid. To mimic the effect of cortical hyperexcitability on visceral hyperalgesia, we injected KCNQ/M channel blocker XE991 into the lateral ventricle of wild type (WT mice. Intracerebroventricular injection of XE991 resulted in increased writhes of WT mice induced by acetic acid, and this effect was reversed by co-injection of the channel opener retigabine. Conclusions Our findings provide evidence that forebrain hyperexcitability confers visceral hyperalgesia, and suppression of central hyperexcitability by activation of KCNQ/M-channel function may provide a therapeutic potential for treatment of abdominal pain syndromes.
Effects of short-term hormonal replacement on learning and on basal forebrain ChAT and TrkA content in ovariectomized rats.

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Espinosa-Raya, Judith; Plata-Cruz, Noemí; Neri-Gómez, Teresa; Camacho-Arroyo, Ignacio; Picazo, Ofir

2011-02-23

It has been proposed that sex steroid hormones improve performance in some cognitive tasks by regulating the basal forebrain cholinergic function. However, the molecular basis of such influence still remains unknown. Current study analyzed the performance of ovariectomized rats in an autoshaping learning task after a short-term treatment with 17β-estradiol (E2: 4 and 40μg/kg) and/or progesterone (P4: 4mg/kg). These results were correlated with basal forebrain choline acetyltransferase (ChAT) and TrkA protein content. The high dose of E2 enhanced both acquisition in the autoshaping task and the content of ChAT and TrkA. P4 treatment increased ChAT and TrkA content without affecting performance of rats in the autoshaping learning task. Interestingly, the continuous and simultaneous administration of E2 plus P4 did not significantly modify behavioral and biochemical evaluated parameters. These results address the influence of both E2 and P4 on cholinergic and TrkA activity and suggest that the effects of ovarian hormones on cognitive performance involve basal forebrain cholinergic neurons. Copyright © 2010 Elsevier B.V. All rights reserved.
Long-lasting novelty-induced neuronal reverberation during slow-wave sleep in multiple forebrain areas.

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Sidarta Ribeiro

2004-01-01

Full Text Available The discovery of experience-dependent brain reactivation during both slow-wave (SW and rapid eye-movement (REM sleep led to the notion that the consolidation of recently acquired memory traces requires neural replay during sleep. To date, however, several observations continue to undermine this hypothesis. To address some of these objections, we investigated the effects of a transient novel experience on the long-term evolution of ongoing neuronal activity in the rat forebrain. We observed that spatiotemporal patterns of neuronal ensemble activity originally produced by the tactile exploration of novel objects recurred for up to 48 h in the cerebral cortex, hippocampus, putamen, and thalamus. This novelty-induced recurrence was characterized by low but significant correlations values. Nearly identical results were found for neuronal activity sampled when animals were moving between objects without touching them. In contrast, negligible recurrence was observed for neuronal patterns obtained when animals explored a familiar environment. While the reverberation of past patterns of neuronal activity was strongest during SW sleep, waking was correlated with a decrease of neuronal reverberation. REM sleep showed more variable results across animals. In contrast with data from hippocampal place cells, we found no evidence of time compression or expansion of neuronal reverberation in any of the sampled forebrain areas. Our results indicate that persistent experience-dependent neuronal reverberation is a general property of multiple forebrain structures. It does not consist of an exact replay of previous activity, but instead it defines a mild and consistent bias towards salient neural ensemble firing patterns. These results are compatible with a slow and progressive process of memory consolidation, reflecting novelty-related neuronal ensemble relationships that seem to be context- rather than stimulus-specific. Based on our current and previous results
In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133

DEFF Research Database (Denmark)

Barraud, Perrine; Stott, Simon; Møllgård, Kjeld

2007-01-01

The stage-specific embryonic antigen 4 (SSEA4) is commonly used as a cell surface marker to identify the pluripotent human embryonic stem (ES) cells. Immunohistochemistry on human embryonic central nervous system revealed that SSEA4 is detectable in the early neuroepithelium, and its expression....... Therefore, we propose that SSEA4 associated with CD133 can be used for both the positive selection and the enrichment of neural stem/progenitor cells from human embryonic forebrain....... decreases as development proceeds. Flow cytometry analysis of forebrain-derived cells demonstrated that the SSEA4-expressing cells are enriched in the neural stem/progenitor cell fraction (CD133(+)), but are rarely codetected with the neural stem cell (NSC) marker CD15. Using a sphere-forming assay, we...
Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis

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Cremer Harold

2011-04-01

Full Text Available Abstract Background Postnatal olfactory bulb (OB neurogenesis involves the generation of granule and periglomerular cells by neural stem cells (NSCs located in the walls of the lateral ventricle (LV. Recent studies show that NSCs located in different regions of the LV give rise to different types of OB neurons. However, the molecular mechanisms governing neuronal specification remain largely unknown and new methods to approach these questions are needed. Results In this study, we refine electroporation of the postnatal forebrain as a technique to perform precise and accurate delivery of transgenes to NSCs located in distinct walls of the LV in the mouse. Using this method, we confirm and expand previous studies showing that NSCs in distinct walls of the LV produce neurons that invade different layers of the OB. Fate mapping of the progeny of radial glial cells located in these distinct LV walls reveals their specification into defined subtypes of granule and periglomerular neurons. Conclusions Our results provide a baseline with which future studies aiming at investigating the role of factors in postnatal forebrain neuronal specification can be compared. Targeted electroporation of defined LV NSC populations will prove valuable to study the genetic factors involved in forebrain neuronal specification.
Anatomical parcellation of the brainstem and cerebellar white matter: a preliminary probabilistic tractography study at 3 T

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Habas, Christophe; Cabanis, Emmanuel A. [UPMC Paris 6, Service de NeuroImagerie, Hopital des Quinze-Vingts, Paris (France)

2007-10-15

The aims of this study were: (1) to test whether higher spatial resolution diffusion tensor images and a higher field strength (3 T) enable a more accurate delineation of the anatomical tract within the brainstem, and, in particular, (2) to try to distinguish the different components of the corticopontocerebellar paths in terms of their cortical origins. The main tracts of the brainstem of four volunteers were studied at 3 T using a probabilistic diffusion tensor imaging (DTI) axonal tracking. The resulting tractograms enabled anatomical well-delineated structures to be identified on the diffusion tensor coloured images. We tracked corticopontine, corticospinal, central tegmental, inferior and superior cerebellopeduncular, transverse, medial lemniscal and, possibly, longitudinal medial fibres. Moreover, DTI tracking allowed a broad delineation of the corticopontocerebellar paths. Diffusion tensor coloured images allow a rapid and reliable access to the white matter broad parcellation of the brainstem and of the cerebellum, which can be completed by fibre tracking. However, a more accurate and exhaustive depiction of the anatomical connectivity within the brainstem requires the application of more sophisticated techniques and tractography algorithms, such as diffusion spectrum imaging. (orig.)
Anatomical parcellation of the brainstem and cerebellar white matter: a preliminary probabilistic tractography study at 3 T

International Nuclear Information System (INIS)

Habas, Christophe; Cabanis, Emmanuel A.

2007-01-01

The aims of this study were: (1) to test whether higher spatial resolution diffusion tensor images and a higher field strength (3 T) enable a more accurate delineation of the anatomical tract within the brainstem, and, in particular, (2) to try to distinguish the different components of the corticopontocerebellar paths in terms of their cortical origins. The main tracts of the brainstem of four volunteers were studied at 3 T using a probabilistic diffusion tensor imaging (DTI) axonal tracking. The resulting tractograms enabled anatomical well-delineated structures to be identified on the diffusion tensor coloured images. We tracked corticopontine, corticospinal, central tegmental, inferior and superior cerebellopeduncular, transverse, medial lemniscal and, possibly, longitudinal medial fibres. Moreover, DTI tracking allowed a broad delineation of the corticopontocerebellar paths. Diffusion tensor coloured images allow a rapid and reliable access to the white matter broad parcellation of the brainstem and of the cerebellum, which can be completed by fibre tracking. However, a more accurate and exhaustive depiction of the anatomical connectivity within the brainstem requires the application of more sophisticated techniques and tractography algorithms, such as diffusion spectrum imaging. (orig.)
Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory

OpenAIRE

Kana Okada; Kayo Nishizawa; Tomoko Kobayashi; Shogo Sakata; Kazuto Kobayashi

2015-01-01

Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer?s disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remai...
Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

Directory of Open Access Journals (Sweden)

C Devin Brisson

Full Text Available Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT imaging in response to 10 minutes of oxygen/glucose deprivation (OGD revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival
Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex

NARCIS (Netherlands)

Gaykema, R.P.A.; Compaan, J.C.; Nyakas, C.; Horvath, E.; Luiten, P.G.M.

1989-01-01

The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the
Brain-stem evoked potentials and noise effects in seagulls.

Science.gov (United States)

Counter, S A

1985-01-01

Brain-stem auditory evoked potentials (BAEP) recorded from the seagull were large-amplitude, short-latency, vertex-positive deflections which originate in the eighth nerve and several brain-stem nuclei. BAEP waveforms were similar in latency and configurations to that reported for certain other lower vertebrates and some mammals. BAEP recorded at several pure tone frequencies throughout the seagull's auditory spectrum showed an area of heightened auditory sensitivity between 1 and 3 kHz. This range was also found to be the primary bandwidth of the vocalization output of young seagulls. Masking by white noise and pure tones had remarkable effects on several parameters of the BAEP. In general, the tone- and click-induced BAEP were either reduced or obliterated by both pure tone and white noise maskers of specific signal to noise ratios and high intensity levels. The masking effects observed in this study may be related to the manner in which seagulls respond to intense environmental noise. One possible conclusion is that intense environmental noise, such as aircraft engine noise, may severely alter the seagull's localization apparatus and induce sonogenic stress, both of which could cause collisions with low-flying aircraft.
The combined effects of forward masking by noise and high click rate on monaural and binaural human auditory nerve and brainstem potentials.

Science.gov (United States)

Pratt, Hillel; Polyakov, Andrey; Bleich, Naomi; Mittelman, Naomi

2004-07-01

To study effects of forward masking and rapid stimulation on human monaurally- and binaurally-evoked brainstem potentials and suggest their relation to synaptic fatigue and recovery and to neuronal action potential refractoriness. Auditory brainstem evoked potentials (ABEPs) were recorded from 12 normally- and symmetrically hearing adults, in response to each click (50 dB nHL, condensation and rarefaction) in a train of nine, with an inter-click interval of 11 ms, that followed a white noise burst of 100 ms duration (50 dB nHL). Sequences of white noise and click train were repeated at a rate of 2.89 s(-1). The interval between noise and first click in the train was 2, 11, 22, 44, 66 or 88 ms in different runs. ABEPs were averaged (8000 repetitions) using a dwell time of 25 micros/address/channel. The binaural interaction components (BICs) of ABEPs were derived and the single, centrally located equivalent dipoles of ABEP waves I and V and of the BIC major wave were estimated. The latencies of dipoles I and V of ABEP, their inter-dipole interval and the dipole magnitude of component V were significantly affected by the interval between noise and clicks and by the serial position of the click in the train. The latency and dipole magnitude of the major BIC component were significantly affected by the interval between noise and clicks. Interval from noise and the click's serial position in the train interacted to affect dipole V latency, dipole V magnitude, BIC latencies and the V-I inter-dipole latency difference. Most of the effects were fully apparent by the first few clicks in the train, and the trend (increase or decrease) was affected by the interval between noise and clicks. The changes in latency and magnitude of ABEP and BIC components with advancing position in the click train and the interactions of click position in the train with the intervals from noise indicate an interaction of fatigue and recovery, compatible with synaptic depletion and replenishing
Sequential change in MRI in two cases with small brainstem infarctions

International Nuclear Information System (INIS)

Masuda, Ryoichi; Fukuda, Osamu; Endoh, Shunro; Takaku, Akira; Suzuki, Takashi; Satoh, Shuji

1987-01-01

Magnetic resonance imaging (MRI) has been found to be very useful for the diagnosis of a small brainstem infarction. However, most reported cases have shown the changes at only the chronic stage. In this report, sequential changes in the MRI in two cases with small brainstem infarctions are presented. In Case 1, a 67-year-old man with a pure sensory stroke on the right side, a small infarcted area was observed at the left medial side of the pontomedullary junction on MRI. In Case 2, a 62-year-old man with a pure motor hemiparesis of the left side, MRI revealed a small infarcted area on the right ventral of the middle pons. The initial changes were confirmed 5 days (Case 1) and 18 hours (Case 2) after the onset of the completed stroke. No abnormal findings could be found in the computed tomography in either case. (author)
Statistical learning of recurring sound patterns encodes auditory objects in songbird forebrain.

Science.gov (United States)

Lu, Kai; Vicario, David S

2014-10-07

Auditory neurophysiology has demonstrated how basic acoustic features are mapped in the brain, but it is still not clear how multiple sound components are integrated over time and recognized as an object. We investigated the role of statistical learning in encoding the sequential features of complex sounds by recording neuronal responses bilaterally in the auditory forebrain of awake songbirds that were passively exposed to long sound streams. These streams contained sequential regularities, and were similar to streams used in human infants to demonstrate statistical learning for speech sounds. For stimulus patterns with contiguous transitions and with nonadjacent elements, single and multiunit responses reflected neuronal discrimination of the familiar patterns from novel patterns. In addition, discrimination of nonadjacent patterns was stronger in the right hemisphere than in the left, and may reflect an effect of top-down modulation that is lateralized. Responses to recurring patterns showed stimulus-specific adaptation, a sparsening of neural activity that may contribute to encoding invariants in the sound stream and that appears to increase coding efficiency for the familiar stimuli across the population of neurons recorded. As auditory information about the world must be received serially over time, recognition of complex auditory objects may depend on this type of mnemonic process to create and differentiate representations of recently heard sounds.
Divergent lactate dehydrogenase isoenzyme profile in cellular compartments of primate forebrain structures.

Science.gov (United States)

Duka, Tetyana; Collins, Zachary; Anderson, Sarah M; Raghanti, Mary Ann; Ely, John J; Hof, Patrick R; Wildman, Derek E; Goodman, Morris; Grossman, Lawrence I; Sherwood, Chet C

2017-07-01

The compartmentalization and association of lactate dehydrogenase (LDH) with specific cellular structures (e.g., synaptosomal, sarcoplasmic or mitochondrial) may play an important role in brain energy metabolism. Our previous research revealed that LDH in the synaptosomal fraction shifts toward the aerobic isoforms (LDH-B) among the large-brained haplorhine primates compared to strepsirrhines. Here, we further analyzed the subcellular localization of LDH in primate forebrain structures using quantitative Western blotting and ELISA. We show that, in cytosolic and mitochondrial subfractions, LDH-B expression level was relatively elevated and LDH-A declined in haplorhines compared to strepsirrhines. LDH-B expression in mitochondrial fractions of the neocortex was preferentially increased, showing a particularly significant rise in the ratio of LDH-B to LDH-A in chimpanzees and humans. We also found a significant correlation between the protein levels of LDH-B in mitochondrial fractions from haplorhine neocortex and the synaptosomal LDH-B that suggests LDH isoforms shift from a predominance of A-subunits toward B-subunits as part of a system that spatially buffers dynamic energy requirements of brain cells. Our results indicate that there is differential subcellular compartmentalization of LDH isoenzymes that evolved among different primate lineages to meet the energy requirements in neocortical and striatal cells. Copyright © 2017 Elsevier Inc. All rights reserved.
Intermittent hypercapnic hypoxia effects on the nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem.

Science.gov (United States)

Vivekanandarajah, Arunnjah; Aishah, Atqiya; Waters, Karen A; Machaalani, Rita

2017-05-01

This study investigated the effects of acute (1 day) vs repeated (4 days) exposure to intermittent hypercapnic hypoxia (IHH) on the immunohistochemical expression of α2, α3, α5, α7, α9 and β2 nicotinic acetylcholine receptor (nAChR) subunits in the developing piglet hippocampus and brainstem medulla, and how prior nicotine exposure alters the response to acute IHH. Five piglet groups included: 1day IHH (1D IHH, n=9), 4days IHH (4D IHH, n=8), controls exposed only to air cycles for 1day (1D Air, n=6) or 4days (4D Air, n=5), and pre-exposed to nicotine for 13days prior to 1day IHH (Nic+1D IHH, n=7). The exposure period alternated 6min of HH (8%O 2 , 7%CO 2 , balance N 2 ) and 6min of air over 48min, while controls were switched from air-to-air. Results showed that: 1. repeated IHH induces more changes in nAChR subunit expression than acute IHH in both the hippocampus and brainstem medulla, 2. In the hippocampus, α2 and β2 changed the most (increased) following IHH and the CA3, CA2 and DG were mostly affected. In the brainstem medulla, α2, α5, α9 and β2 were changed (decreased) in most nuclei with the hypoglossal and nucleus of the solitary tract being mostly affected. 3. Pre-exposure to nicotine enhanced the changes in the hippocampus but dampened those in the brainstem medulla. These findings indicate that the nAChRs (predominantly with the α2/β2 complex) are affected by IHH in critical hippocampal and brainstem nuclei during early brain development, and that pre-exposure to nicotine alters the pattern of susceptibility to IHH. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide.

Science.gov (United States)

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Shirao, Satoshi; Suzuki, Michiyasu

2011-01-01

Ebselen is a mimic of glutathione peroxidase that reacts with peroxynitrite and inhibits nitric oxide (NO) synthase. Ebselen has beneficial effects on the neurological outcome of patients with stroke. In this study, the mechanisms by which ebselen can elicit neuroprotective effects against ischemic brain injury were investigated in male Wistar rats. Experimental forebrain ischemia was induced by bilateral common carotid artery occlusion with hemorrhagic hypotension. Ebselen was administered to animals in the treatment group 2 hours prior to the induction of forebrain ischemia, and placebo was administered in the control group. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Cortical extracellular levels of excitatory amino acids (EAAs) and NO were evaluated using in vivo microdialysis. Neuronal damage in the CA1 subfield of the hippocampus was assessed in brains harvested after a 24-hour period of survival. CBF did not recover to normal physiological levels after ischemic insults in either the control or treatment groups. The differences in the sequential changes in extracellular EAA and NO levels between groups were not statistically significant. There was a significantly larger mean density of intact, undamaged neurons in the CA1 subfield in the treatment group than in the control group. The neuroprotective effects of ebselen were reflected in the histological findings, without significant inhibition of glutamate release or NO synthesis during the acute phase of experimentally induced cerebral ischemia.
Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing.

Science.gov (United States)

Abulebda, Kamal; Patel, Vinit J; Ahmed, Sheikh S; Tori, Alvaro J; Lutfi, Riad; Abu-Sultaneh, Samer

2017-10-28

The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.
Boxing sparring complicated by an acute subdural haematoma and brainstem haemorrhage.

Science.gov (United States)

Hart, Michael G; Trivedi, Rikin A; Hutchinson, Peter J

2012-10-01

A professional boxer developed an acute subdural haematoma after boxing sparring. Despite timely surgical decompression, he had a poor overall outcome predominantly from a delayed brainstem haematoma. Magnetic resonance imaging (MRI) was used to elucidate the pathophysiology of the patients' injury and clinical condition.
MRI findings of the brainstem of the neuro-Behcet syndrome

Energy Technology Data Exchange (ETDEWEB)

Fujiki, Naoto; Tashiro, Kunio; Yamada, Takayoshi; Ito, Kazunori; Honma, Sanae; Doi, Shizuki; Moriwaka, Fumio

1987-10-01

We reported three cases of neuro-Behcet's syndrome which showed brainstem lesions on MRI compatible with the clinical symptoms. In Case 1, MRI showed a large, abnormal signal-intensity area in the pons and small, abnormal signal-intensity areas at the right cerebral peduncle, the bilateral basal ganglia, and the left thalamus. These lesions disappeared on MRI, in accordance with the remission of clinical symptoms. On the other hand, CT showed no positive findings. In Case 2, an abnormal signal-intensity area was disclosed at the left cerebral peduncle on MRI. This lesion was also identified on the CT scan. In Case 3, an abnormal signal-intensity area was present in the pons on MRI. In this case, CT showed no positive findings. In Cases 2 and 3, these lesions seemed to represent inflammatory or necrotic areas attributable to vasculitis;however, the extensive brainstem lesion seen on the MRI of Case 1 was a quite unique finding, for which no exact pathophysiological explanation is possible at the present time.
Ablation of CaV2.1 Voltage-Gated Ca2+ Channels in Mouse Forebrain Generates Multiple Cognitive Impairments

Science.gov (United States)

Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

2013-01-01

Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels located at the presynaptic membrane are known to control a multitude of Ca2+-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic CaV2.1 mouse models. Global CaV2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of CaV2.1 Ca2+ channels for complex behaviour in adult mice. Consequently we established a forebrain specific CaV2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of CaV2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific CaV2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional CaV2.1 knock-out model that is most suitable for analysing the in vivo functions of CaV2.1 in the adult murine forebrain. PMID:24205277
The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study.

Science.gov (United States)

Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D

2012-03-01

In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured anatomically magnetic resonance imaging. The relations of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages 4 to 17). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volume of the right thalamus is significantly larger than that of the left in both genders, with greater rightward asymmetry and greater thalamus to grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volume. Larger thalami were associated with higher Verbal IQ. These normative pediatric data are of value to researchers who study these regions in neurodevelopmental disorders.
Features of the brainstem and tentorial foramen relationship and their practical value

Directory of Open Access Journals (Sweden)

O. V. Redyakina

2016-11-01

Full Text Available Objective. Establish the morphological features and practical significance of the tentorial-stem relationship from the position of individual anatomical variability. Methods: head morphometry, macro and microscopic examination of the brainstem, morphometry of the brainstem and its departments, tentorial aperture morphometry, foramen magnum craniometry, manufacture of corrosion molds of the posterior cranial fossa, statistical processing of the results, computer-graphic modeling of the brainstem and surrounding formations. Results. In the course of the study, the features of the individual variability of the tentorial foramen form were established, namely: shortened-expanded and oval-convex forms were defined in brachycephalic; in dolichocephalic - oblong-narrowed and elongated-conical. At the same time, a number of existing sizes and forms of the tentorial-stem spaces were noted. Among them, four main ones are described: front, side (right and left and rear. They have individual characteristics. Thus, in the brachycephalic we define lateral holes, due to the convexity of the tentorial margins. In dolichocephalic - front and back gaps, depending on the characteristics of their elongations. The obtained data are of great importance for the craniotopographic justification of the tentorial-stem wedges, which are formed with tumors which located here. In our opinion, tumors have the greatest possibility of passage through the left or right lateral intervals in people with a brachymorph form of the head, and through the anterior and posterior intervals - in people with meso- and dolichomorph forms of the head.
Blast overpressure induced axonal injury changes in rat brainstem and spinal cord

Directory of Open Access Journals (Sweden)

Srinivasu Kallakuri

2015-01-01

Full Text Available Introduction: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s of blast overpressure (OP induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM tracts of cervical spinal cord are limited. Objective: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP. Materials and Methods: Sagittal brainstem sections and horizontal cervical spinal cord sections from blast and sham animals were stained by neurofilament light (NF-L chain and beta amyloid precursor protein immunocytochemistry and observed for axonal injury changes. Results: Observations from this preliminary study demonstrate axonal injury changes in the form of prominent swellings, retraction bulbs, and putative signs of membrane disruptions in the brainstem and cervical spinal cord WM tracts of rats subjected to blast OP. Conclusions: Prominent axonal injury changes following the blast OP exposure in brainstem and cervical spinal WM tracts underscores the need for careful evaluation of blast induced injury changes and associated symptoms. NF-L immunocytochemistry can be considered as an additional tool to assess the blast OP induced axonal injury.
MRI and associated clinical characteristics of EV71-induced brainstem encephalitis in children with hand-foot-mouth disease

International Nuclear Information System (INIS)

Zeng, Hongwu; Gan, Yungen; Wen, Feiqiu; Huang, Wenxian

2012-01-01

This study was conducted to investigate MRI and associated clinical characteristics of brainstem encephalitis induced by enterovirus 71 (EV71) in children with hand-foot-mouth disease (HFMD). We analyzed clinical and imaging data from 42 HFMD cases with EV71-induced brainstem encephalitis. All patients underwent plain and enhanced MRI cranial scans and were placed into one of two groups according to MRI enhancement results, an enhanced group or a nonenhanced group. Thirty-two cases were positive on MRI exam. The primary location of the lesion for brainstem encephalitis was the dorsal pons and medulla oblongata (32 cases), followed by the cerebellar dentate nucleus (8 cases), midbrain (5 cases), and thalamus (2 cases). Plain T1-weighted images showed isointense or hypointense signals, and T2-weighted images showed isointense and hyperintense signals. Enhanced MRI scans showed that 12 cases had slight to moderate enhancement; 4 of these were normal on plain scan. The time from MRI examination to disease onset was statistically different between the enhanced (n = 12) and nonenhanced (n = 21) groups with a mean of 7.67 days (SD = 1.07) vs 11.95 days (SD = 5.33), respectively. The most common neurological symptoms for brainstem encephalitis were myoclonus and tremor. The greater the area of affected brain, the more severe the clinical symptoms were. The locations of EV71-induced HFMD-associated brainstem encephalitis lesions are relatively specific. Enhanced MRI scans could also identify the lesions missed by early plain scans. MRI scans can provide important information for clinical evaluation and treatment. (orig.)
MRI and associated clinical characteristics of EV71-induced brainstem encephalitis in children with hand-foot-mouth disease

Energy Technology Data Exchange (ETDEWEB)

Zeng, Hongwu; Gan, Yungen [Shenzhen Children' s Hospital, Department of Radiology, Shenzhen (China); Wen, Feiqiu [Shenzhen Children' s Hospital, Department of Neurology, Shenzhen (China); Huang, Wenxian [Shenzhen Children' s Hospital, Department of Respiratory, Shenzhen (China)

2012-06-15

This study was conducted to investigate MRI and associated clinical characteristics of brainstem encephalitis induced by enterovirus 71 (EV71) in children with hand-foot-mouth disease (HFMD). We analyzed clinical and imaging data from 42 HFMD cases with EV71-induced brainstem encephalitis. All patients underwent plain and enhanced MRI cranial scans and were placed into one of two groups according to MRI enhancement results, an enhanced group or a nonenhanced group. Thirty-two cases were positive on MRI exam. The primary location of the lesion for brainstem encephalitis was the dorsal pons and medulla oblongata (32 cases), followed by the cerebellar dentate nucleus (8 cases), midbrain (5 cases), and thalamus (2 cases). Plain T1-weighted images showed isointense or hypointense signals, and T2-weighted images showed isointense and hyperintense signals. Enhanced MRI scans showed that 12 cases had slight to moderate enhancement; 4 of these were normal on plain scan. The time from MRI examination to disease onset was statistically different between the enhanced (n = 12) and nonenhanced (n = 21) groups with a mean of 7.67 days (SD = 1.07) vs 11.95 days (SD = 5.33), respectively. The most common neurological symptoms for brainstem encephalitis were myoclonus and tremor. The greater the area of affected brain, the more severe the clinical symptoms were. The locations of EV71-induced HFMD-associated brainstem encephalitis lesions are relatively specific. Enhanced MRI scans could also identify the lesions missed by early plain scans. MRI scans can provide important information for clinical evaluation and treatment. (orig.)
Analysis of NR3A receptor subunits in human native NMDA receptors

DEFF Research Database (Denmark)

Nilsson, Anna; Eriksson, Maria; Muly, E Chris

2007-01-01

NR3A, representing the third class of NMDA receptor subunits, was first studied in rats, demonstrating ubiquitous expression in the developing central nervous system (CNS), but in the adult mainly expressed in spinal cord and some forebrain nuclei. Subsequent studies showed that rodent and non-human...... primate NR3A expression differs. We have studied the distribution of NR3A in the human CNS and show a widespread distribution of NR3A protein in adult human brain. NR3A mRNA and protein were found in all regions of the cerebral cortex, and also in the subcortical forebrain, midbrain and hindbrain. Only...... very low levels of NR3A mRNA and protein could be detected in homogenized adult human spinal cord, and in situ hybridization showed that expression was limited to ventral motoneurons. We found that NR3A is associated with NR1, NR2A and NR2B in adult human CNS, suggesting the existence of native NR1-NR2...
Retrospective analysis of 104 histologically proven adult brainstem gliomas: clinical symptoms, therapeutic approaches and prognostic factors

International Nuclear Information System (INIS)

Reithmeier, Thomas; Kuzeawu, Aanyo; Hentschel, Bettina; Loeffler, Markus; Trippel, Michael; Nikkhah, Guido

2014-01-01

Adult brainstem gliomas are rare primary brain tumors (<2% of gliomas). The goal of this study was to analyze clinical, prognostic and therapeutic factors in a large series of histologically proven brainstem gliomas. Between 1997 and 2007, 104 patients with a histologically proven brainstem glioma were retrospectively analyzed. Data about clinical course of disease, neuropathological findings and therapeutic approaches were analyzed. The median age at diagnosis was 41 years (range 18-89 years), median KPS before any operative procedure was 80 (range 20-100) and median survival for the whole cohort was 18.8 months. Histopathological examinations revealed 16 grade I, 31 grade II, 42 grade III and 14 grade IV gliomas. Grading was not possible in 1 patient. Therapeutic concepts differed according to the histopathology of the disease. Median overall survival for grade II tumors was 26.4 months, for grade III tumors 12.9 months and for grade IV tumors 9.8 months. On multivariate analysis the relative risk to die increased with a KPS ≤ 70 by factor 6.7, with grade III/IV gliomas by the factor 1.8 and for age ≥ 40 by the factor 1.7. External beam radiation reduced the risk to die by factor 0.4. Adult brainstem gliomas present with a wide variety of neurological symptoms and postoperative radiation remains the cornerstone of therapy with no proven benefit of adding chemotherapy. Low KPS, age ≥ 40 and higher tumor grade have a negative impact on overall survival
Survey of the Knowledge of Brainstem Death and Attitude Toward Organ Donation Among Relations of Neurosurgical Patients in Nigeria.

Science.gov (United States)

Rabiu, T B; Oshola, H A; Adebayo, B O

2016-01-01

Organ transplantation is a developing field in Nigeria, and availability of organs for donation would be a determining factor of the success of the transplant programs. Patients with brainstem death (BSD) are a major source of organs for transplantation. The level of knowledge of BSD as well as attitudes toward organ donation are very important determinants of people's willingness or otherwise to donate organs. We conducted a survey of relations of our in-service neurosurgical patients to assess their knowledge of brainstem death and attitude toward organ donation. To our knowledge, this is the first study of its kind among the growing Nigerian neurosurgery patient and patient-relations population. Convenience sampling of randomly selected relations of neurosurgical patients on admission using interviewer-administered questionnaires was performed. Demographic information and information about brainstem death, attitude toward brainstem death, knowledge of organ donation, and attitude toward organ donation were obtained. The study comprised 127 respondents with a mean age of 36 years (range, 19-72). The majority of the respondents (87, 62.4%) were Christians, 122 (96.1%) were Yorubas, and 66 (52.0%) were women. Eighty-five (66.9%) of the respondents had at least a secondary level of education, and 77 (60.6%) were of low socioeconomic status. Twenty-eight (22.2%) of the respondents had heard of brainstem death. Twenty-six (92.9%) of those who had heard of brainstem death believed that the brain could die long before life finally ceases. One hundred twenty-five (98.4%) of the respondents believed that death only occurs when both breathing and heartbeat stop, and 107 (83.6%) would agree with the physician on a diagnosis of brainstem death in the relation. Sixty-five (51.2%) would want such patients put on a ventilator, and, of these, 43 (66.2%) would want such patients on the ventilator in hope that he or she may recover. One hundred twelve (88.2%) of the relations were
Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

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Hasegawa Shunsuke

2009-03-01

Full Text Available Abstract Background Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII in learning, memory and long-term potentiation (LTP. However, previous studies have also shown that alpha-CaMKII (+/- heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes. Results We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/- heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression. Conclusion Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects
The basal forebrain cholinergic system in aging and dementia : Rescuing cholinergic neurons from neurotoxic amyloid-beta 42 with memantine

NARCIS (Netherlands)

Nyakas, Csaba; Granic, Ivica; Halmy, Laszlo G.; Banerjee, Pradeep; Luiten, Paul G. M.

2011-01-01

The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of
What makes humanity humane

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Pribram, Karl H

2006-01-01

Scientific and popular lore have promulgated a connection between emotion and the limbic forebrain. However, there are a variety of structures that are considered limbic, and disagreement as to what is meant by "emotion". This essay traces the initial studies upon which the connection between emotion and the limbic forebrain was based and how subsequent experimental evidence led to confusion both with regard to brain systems and to the behaviors examined. In the process of sorting out the bas...
Effectiveness of interferon-[beta], ACNU, and radiation therapy in pediatric patients with brainstem glioma

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Wakabayashi, Toshihiko; Yoshida, Jun; Mizuno, Masaaki; Sugita, Kenichiro [Nagoya Univ. (Japan). Faculty of Medicine; Kito, Akira

1992-12-01

Sixteen pediatric patients with brainstem glioma were treated with a combination of interferon-[beta], 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl -3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and radiation therapy (IAR therapy). All patients received 1-1.5 million IU/day of interferon-[beta] intravenously for 1 week of each 6-week cycle. In addition, ACNU (2-3 mg/kg) was given on the 2nd day of each cycle. Conventional focal irradiation (1.5-2 Gy/day for 5 days to a total dosage of 40-60 Gy) was administered beginning on day 3. Patients underwent at least two 6-week cycles. Adverse effects included nausea, vomiting, and myelosuppression, but were mild and transient. Response to treatment was evaluated by the reduction in tumor size measured on postcontrast computed tomographic scans and magnetic resonance images. Responses occurred in 10 of 11 patients with the intrinsic type of brainstem glioma, including three complete and seven partial responses. Two of the five patients with exophytic type gliomas partially responded. The median survival was 15.7 months, a remarkable improvement over the natural course of this disease. These results indicate that IAR therapy is a useful primary treatment for pediatric patients with brainstem gliomas. (author).
Hypertensive brainstem encephalopathy involving deep supratentorial regions: does only blood pressure matter?

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Jong-Ho Park

2010-04-01

Full Text Available We report on a 42-year-old female patient who presented with high arterial blood pressure of 245/150 mmHg and hypertensive brainstem encephalopathy that involved the brainstem and extensive supratentorial deep gray and white matter. The lesions were nearly completely resolved several days after stabilization of the arterial blood pressure. Normal diffusion-weighted imaging findings and high apparent diffusion coefficient values suggested that the main pathomechanism was vasogenic edema owing to severe hypertension. On the basis of a literature review, the absolute value of blood pressure or whether the patient can control his/her blood pressure seems not to be associated with the degree of the lesions evident on magnetic resonance imaging. It remains to be determined if the acceleration rate and the duration of elevated arterial blood pressure might play a key role in the development of the hypertensive encephalopathy pattern.
Intracranial neurenteric cyst traversing the brainstem

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Jasmit Singh

2015-01-01

Full Text Available Neurenteric cysts (NECs, also called enterogenous cysts, are rare benign endodermal lesions of the central nervous system that probably result from separation failure of the notochord and upper gastrointestinal tract. Most frequently they are found in the lower cervical spine or the upper thoracic spine. Intracranial occurrence is rare and mostly confined to infratentorial compartment, in prepontine region [51%]. Other common locations are fourth ventricle and cerebellopontine angle. There are few reports of NEC in medulla or the cerebellum. Because of the rarity of the disease and common radiological findings, they are misinterpreted as arachnoid or simple cysts until the histopathological confirmation, unless suspected preoperatively. We herein report a rare yet interesting case of intracranial NEC traversing across the brainstem.
Astrocyte-secreted factors modulate a gradient of primary dendritic arbors in nucleus laminaris of the avian auditory brainstem.

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Matthew J Korn

Full Text Available Neurons in nucleus laminaris (NL receive binaural, tonotopically matched input from nucleus magnocelluaris (NM onto bitufted dendrites that display a gradient of dendritic arbor size. These features improve computation of interaural time differences, which are used to determine the locations of sound sources. The dendritic gradient emerges following a period of significant reorganization at embryonic day 15 (E15, which coincides with the emergence of astrocytes that express glial fibrillary acidic protein (GFAP in the auditory brainstem. The major changes include a loss of total dendritic length, a systematic loss of primary dendrites along the tonotopic axis, and lengthening of primary dendrites on caudolateral NL neurons. Here we have tested whether astrocyte-derived molecules contribute to these changes in dendritic morphology. We used an organotypic brainstem slice preparation to perform repeated imaging of individual dye-filled NL neurons to determine the effects of astrocyte-conditioned medium (ACM on dendritic morphology. We found that treatment with ACM induced a decrease in the number of primary dendrites in a tonotopically graded manner similar to that observed during normal development. Our data introduce a new interaction between astrocytes and neurons in the auditory brainstem and suggest that these astrocytes influence multiple aspects of auditory brainstem maturation.

Brainstem encephalitis and acute polyneuropathy associated with hepatitis E infection.

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Salim, Omar Jabbar; Davidson, Amy; Li, Kathy; Leach, John Paul; Heath, Craig

2017-09-11

A 59-year-old man presented with feverish illness. His Glasgow Coma Scale was 15, had reduced visual acuity in the left eye with partial left ptosis and mild left hemiparesis with an extensor left plantar. Over 48 hours, he accrued multiple cranial nerves palsies and progressed to a flaccid paralysis necessitating admission to an intensive care unit.Cerebrospinal fluid (CSF) study showed 20 lymphocytes and raised protein. Viral and bacterial PCRs were negative. Samples for Lyme, blood-borne viruses, syphilis and autoantibodies were also negative. MRI brain showed T2 abnormalities within the brainstem. Nerve conduction studies revealed an acute motor and sensory axonal neuropathy pattern of Guillian Barre Syndrome (GBS). The patient was treated for both infective and inflammatory causes of brainstem encephalitis and GBS.Retrospective studies confirmed the presence of hepatitis E virus (HEV) RNA in CSF and serum studies showed positive HEV IgG and IgM prior to intravenous infusion. After 3 months of intensive rehabilitation, the patient was discharged home walking with a frame. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

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Zhang, Wen; Peterson, Matthew; Beyer, Barbara; Frankel, Wayne N.

2014-01-01

Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability. PMID:24523563
Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

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Katsuo Kimura

Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.
Correlation between gadolinium-diethylenetriaminepentaacetic acid contrast enhancement and thallium-201 chloride uptake in pediatric brainstem glioma.

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Maria, B L; Drane, W B; Quisling, R J; Hoang, K B

1997-09-01

We previously showed that thallium-201 (201Tl) chloride is accumulated in over 75% of brain tumors, including brainstem gliomas. The imaging of 201Tl with single photon emission computed tomography (SPECT) may require an abnormal increase in permeability of tumor vessels to allow penetration of the blood-brain barrier. To test this hypothesis, we evaluated the correlation between gadolinium enhancement and the degree of 201Tl uptake on SPECT and the contributions of either gadolinium enhancement or 201Tl uptake to the prognosis in children with brainstem gliomas. Forty-two sets of paired SPECT scans and magnetic resonance imaging (MRI) scans were obtained longitudinally in 13 cases. Altogether, 31 of 42 pairs (74%) of scans showed concordance between the presence of gadolinium enhancement and 201Tl uptake. There were no cases that demonstrated 201Tl uptake but lacked gadolinium enhancement. The results indicate that 201Tl SPECT is of value primarily when brainstem tumors have vessels that are demonstrably permeable to gadolinium, prior to or as a result of radiotherapy.
Low-frequency versus high-frequency synchronisation in chirp-evoked auditory brainstem responses

DEFF Research Database (Denmark)

Rønne, Filip Munch; Gøtsche-Rasmussen, Kristian

2011-01-01

This study investigates the frequency specific contribution to the auditory brainstem response (ABR) of chirp stimuli. Frequency rising chirps were designed to compensate for the cochlear traveling wave delay, and lead to larger wave-V amplitudes than for click stimuli as more auditory nerve fibr...
Cortical and brainstem plasticity in Tourette syndrome and obsessive-compulsive disorder.

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Suppa, Antonio; Marsili, Luca; Di Stasio, Flavio; Berardelli, Isabella; Roselli, Valentina; Pasquini, Massimo; Cardona, Francesco; Berardelli, Alfredo

2014-10-01

Gilles de la Tourette syndrome is characterized by motor/vocal tics commonly associated with psychiatric disorders, including obsessive-compulsive disorder. We investigated primary motor cortex and brainstem plasticity in Tourette patients, exposed and unexposed to chronic drug treatment, with and without psychiatric disturbances. We also investigated primary motor cortex and brainstem plasticity in obsessive-compulsive disorder. We studied 20 Tourette patients with and without psychiatric disturbances, 15 with obsessive-compulsive disorder, and 20 healthy subjects. All groups included drug-naïve patients. We conditioned the left primary motor cortex with intermittent/continuous theta-burst stimulation and recorded motor evoked potentials. We conditioned the supraorbital nerve with facilitatory/inhibitory high-frequency stimulation and recorded the blink reflex late response area. In healthy subjects, intermittent theta-burst increased and continuous theta-burst stimulation decreased motor evoked potentials. Differently, intermittent theta-burst failed to increase and continuous theta-burst stimulation failed to decrease motor evoked potentials in Tourette patients, with and without psychiatric disturbances. In obsessive-compulsive disorder, intermittent/continuous theta-burst stimulation elicited normal responses. In healthy subjects and in subjects with obsessive-compulsive disorder, the blink reflex late response area increased after facilitatory high-frequency and decreased after inhibitory high-frequency stimulation. Conversely, in Tourette patients, with and without psychiatric disturbances, facilitatory/inhibitory high-frequency stimulation left the blink reflex late response area unchanged. Theta-burst and high-frequency stimulation elicited similar responses in drug-naïve and chronically treated patients. Tourette patients have reduced plasticity regardless of psychiatric disturbances. These findings suggest that abnormal plasticity contributes to the
SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex

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Brøchner, Christian B; Møllgård, Kjeld

2016-01-01

The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA-4 and YKL-40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double-...
Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

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Patrick Aldrin-Kirk

Full Text Available Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable
Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

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Agnete Kirkeby

2012-06-01

Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.
Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

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Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael; Ayupova, Dina A.; Lindhout, Darrin A.; Higbee, Jared; Kutach, Alan; Joo, William; Gao, Zhengyu; Fu, Diana; To, Carmen; Mondal, Kalyani; Li, Betty; Kekatpure, Avantika; Wang, Marilyn; Laird, Teresa; Horner, Geoffrey; Chan, Jackie; McEntee, Michele; Lopez, Manuel; Lakshminarasimhan, Damodharan; White, Andre; Wang, Sheng-Ping; Yao, Jun; Yie, Junming; Matern, Hugo; Solloway, Mark; Haldankar, Raj; Parsons, Thomas; Tang, Jie; Shen, Wenyan D.; Alice Chen, Yu; Tian, Hui; Allan, Bernard B.

2017-09-27

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptor for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.
Relationship between brainstem neurodegeneration and clinical impairment in traumatic spinal cord injury

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Patrick Grabher

2017-01-01

Conclusion: Neurodegeneration, indicated by volume loss and myelin reductions, is evident in major brainstem pathways and nuclei following traumatic SCI; the magnitude of these changes relating to clinical impairment. Thus, quantitative MRI protocols offer new targets, which may be used as neuroimaging biomarkers in treatment trials.
Development of Brainstem-Evoked Responses in Congenital Auditory Deprivation

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J. Tillein

2012-01-01

Full Text Available To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs and hearing controls (HCs were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed. Electrically evoked auditory brainstem responses (E-ABRs were recorded with monopolar stimulation at different current levels. CDCs demonstrated extensive development of E-ABRs, from first signs of responses at postnatal (p.n. day 3 through appearance of all waves of brainstem response at day 8 p.n. to mature responses around day 90 p.n.. Wave I of E-ABRs could not be distinguished from the artifact in majority of CDCs, whereas in HCs, it was clearly separated from the stimulus artifact. Waves II, III, and IV demonstrated higher thresholds in CDCs, whereas this difference was not found for wave V. Amplitudes of wave III were significantly higher in HCs, whereas wave V amplitudes were significantly higher in CDCs. No differences in latencies were observed between the animal groups. These data demonstrate significant postnatal subcortical development in absence of hearing, and also divergent effects of deafness on early waves II–IV and wave V of the E-ABR.
The different effects of over-expressing murine NMDA receptor 2B subunit in the forebrain on conditioned taste aversion.

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Li, Shijia; Gu, Yiran; Meng, Bo; Mei, Bing; Li, Fei

2010-09-10

The glutamate transmission system and the N-methyl-D-aspartate receptor (NMDA-R), in particular its 2B subunit (NR2B), have been reported to be possibly related to taste memory as a result of treatment with NMDA antagonists and agonists. In order to further study the role of the NR2B subunit in gustation memory, we applied four different taste aversive tasks to observe the behavior of a transgenic mice model in which the NR2B subunit was specifically over-expressed in the forebrain. We found that in both short- and long-term conditioned taste aversion (CTA) experiments, mice with forebrain expression of the NR2B transgene (Tg) showed significantly enhanced CTA 2 days after training. However, both the Tg and the wild-type (Wt) mice shared the same level of aversive memory on the 30th day after training. In both fast and slow extinction experiments, Tg mice maintained a higher CTA memory than that of control mice in most extinction trials. The third experiment, which involved testing the memory for familiar taste, demonstrated that NR2B augmentation had no benefit on the latent inhibition (LI) of CTA. In addition, the last experiment (two-taste LI) showed a suppression of enhanced CTA in Tg mice when the mice were exposed to both novel and familiar tastes. These data suggested that forebrain NR2B over-expression had different effects on gustatory learning and memory. The transgenic animals were only sensitive to novel but not familiar tastes, and up-regulation of NR2B resulted in enhanced CTA function for only a short period of time. 2010 Elsevier B.V. All rights reserved.
Ablation of cdk4 and cdk6 affects proliferation of basal progenitor cells in the developing dorsal and ventral forebrain.

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Grison, Alice; Gaiser, Carine; Bieder, Andrea; Baranek, Constanze; Atanasoski, Suzana

2018-03-23

Little is known about the molecular players driving proliferation of neural progenitor cells (NPCs) during embryonic mouse development. Here, we demonstrate that proliferation of NPCs in the developing forebrain depends on a particular combination of cell cycle regulators. We have analyzed the requirements for members of the cyclin-dependent kinase (cdk) family using cdk-deficient mice. In the absence of either cdk4 or cdk6, which are both regulators of the G1 phase of the cell cycle, we found no significant effects on the proliferation rate of cortical progenitor cells. However, concomitant loss of cdk4 and cdk6 led to a drastic decrease in the proliferation rate of NPCs, specifically the basal progenitor cells of both the dorsal and ventral forebrain at embryonic day 13.5 (E13.5). Moreover, basal progenitors in the forebrain of Cdk4;Cdk6 double mutant mice exhibited altered cell cycle characteristics. Cdk4;cdk6 deficiency led to an increase in cell cycle length and cell cycle exit of mutant basal progenitor cells in comparison to controls. In contrast, concomitant ablation of cdk2 and cdk6 had no effect on the proliferation of NCPs. Together, our data demonstrate that the expansion of the basal progenitor pool in the developing telencephalon is dependent on the presence of distinct combinations of cdk molecules. Our results provide further evidence for differences in the regulation of proliferation between apical and basal progenitors during cortical development. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.
Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

Science.gov (United States)

Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

2013-01-01

Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.1 mouse models. Global Ca(V)2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V)2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V)2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V)2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V)2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V)2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V)2.1 in the adult murine forebrain.
Quantitative Magnetic Resonance Imaging of Brainstem Volumes, Plaques, and Surface Area in the Occipital Regions of Patients with Multiple Sclerosis

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Alper, F.; Kantarci, M.; Altunkaynak, E.; Varoglu, A. O.; Karaman, A.; Oral, E.; Okur, A. [Ataturk Univ., Erzurum (Turkey). Depts. of Radiology, Histology, Neurology and Embryology, Psychiatry

2006-07-15

Purpose: To determine brainstem volumes, number of plaques, and surface areas in the occipital lobes of patients with relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and to investigate whether there is any correlation between brainstem volume and the number/surface areas of plaque in the occipital lobes. Material and Methods: Magnetic resonance imaging was obtained on 14 relapsing-remitting (RR) and 13 secondary progressive (SP) MS patients and 26 female control subjects. The Cavalieri method was used by modern design stereology to measure brainstem volume. The point-counting grid was used to evaluate sclerotic plaque surface areas in the occipital lobe. The number of plaques in the imaging section was calculated. Results: Brainstem volumes for RR and SP with multiple sclerosis and control subjects were 3647 mm{sup 3} , 3515 mm{sup 3} , and 4517 mm{sup 3} , respectively. Mean number of plaques in the right-left occipital lobe was found to be 2.7-3.4 in RR-MS and 5.2-2.8 in SP-MS. Mean plaque surface area in the right-left occipital lobe was determined to be 58.52-88.24 mm{sup 2} in RR MS and 124.3-64.82 mm{sup 2} in SP MS. Brainstem volumes were significantly reduced in both groups of patients with MS compared to controls ( P <0.01). Conclusion: Magnetic-resonance-estimated volume and surface area values in multiple sclerosis may facilitate our understanding of the clinical situation of patients and provide a simple index for evaluating therapeutic efficiency.
Quantitative Magnetic Resonance Imaging of Brainstem Volumes, Plaques, and Surface Area in the Occipital Regions of Patients with Multiple Sclerosis

International Nuclear Information System (INIS)

Alper, F.; Kantarci, M.; Altunkaynak, E.; Varoglu, A. O.; Karaman, A.; Oral, E.; Okur, A.

2006-01-01

Purpose: To determine brainstem volumes, number of plaques, and surface areas in the occipital lobes of patients with relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and to investigate whether there is any correlation between brainstem volume and the number/surface areas of plaque in the occipital lobes. Material and Methods: Magnetic resonance imaging was obtained on 14 relapsing-remitting (RR) and 13 secondary progressive (SP) MS patients and 26 female control subjects. The Cavalieri method was used by modern design stereology to measure brainstem volume. The point-counting grid was used to evaluate sclerotic plaque surface areas in the occipital lobe. The number of plaques in the imaging section was calculated. Results: Brainstem volumes for RR and SP with multiple sclerosis and control subjects were 3647 mm 3 , 3515 mm 3 , and 4517 mm 3 , respectively. Mean number of plaques in the right-left occipital lobe was found to be 2.7-3.4 in RR-MS and 5.2-2.8 in SP-MS. Mean plaque surface area in the right-left occipital lobe was determined to be 58.52-88.24 mm 2 in RR MS and 124.3-64.82 mm 2 in SP MS. Brainstem volumes were significantly reduced in both groups of patients with MS compared to controls ( P <0.01). Conclusion: Magnetic-resonance-estimated volume and surface area values in multiple sclerosis may facilitate our understanding of the clinical situation of patients and provide a simple index for evaluating therapeutic efficiency
The Input-Output Relationship of the Cholinergic Basal Forebrain

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Matthew R. Gielow

2017-02-01

Full Text Available Basal forebrain cholinergic neurons influence cortical state, plasticity, learning, and attention. They collectively innervate the entire cerebral cortex, differentially controlling acetylcholine efflux across different cortical areas and timescales. Such control might be achieved by differential inputs driving separable cholinergic outputs, although no input-output relationship on a brain-wide level has ever been demonstrated. Here, we identify input neurons to cholinergic cells projecting to specific cortical regions by infecting cholinergic axon terminals with a monosynaptically restricted viral tracer. This approach revealed several circuit motifs, such as central amygdala neurons synapsing onto basolateral amygdala-projecting cholinergic neurons or strong somatosensory cortical input to motor cortex-projecting cholinergic neurons. The presence of input cells in the parasympathetic midbrain nuclei contacting frontally projecting cholinergic neurons suggest that the network regulating the inner eye muscles are additionally regulating cortical state via acetylcholine efflux. This dataset enables future circuit-level experiments to identify drivers of known cortical cholinergic functions.
Clinical analysis of the outcome of patients with brainstem hemorrhage

International Nuclear Information System (INIS)

Arimoto, Hirohiko; Takasato, Yoshio; Masaoka, Hiroyuki

2008-01-01

To identify prognostic factors in patients with brainstem hemorrhage, we analyzed their clinical symptoms and laboratory data on admission to our hospital. In 70 patients with brainstem hemorrhage (51 men and 19 women aged 29-93, with a mean of 59 gears) who had been admitted to our hospital from 1995 to 2000, we statistically evaluated the association of the outcome with their age and clinical symptoms on admission, blood glucose levels and white blood counts within 6 hours of admission, and the volume and extent of hematoma, concomitant hydrocephalus, and intraventricular perforation on admission CT scans. The mortality tended to be higher, but not significantly (P=0.07), in patients aged 70 years or older (83%) than in those aged less than 70 years (55%). Quadriplegia or decerebrate rigidity (P 2 or higher (P<0.01) on admission were significantly correlated with the prognosis. Hematoma volumes of 6 ml or larger on CT scans were most strongly correlated with the prognosis (P<0.001). Central hematoma and hematoma with extension to the midbrain, thalamus, or medulla oblongata (P<0.05), as well as hemorrhage complicated by hydrocephalus or intraventricular perforation (P<0.01), were correlated with the prognosis. (author)
The nucleus pararaphales in the human, chimpanzee, and macaque monkey.

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Baizer, Joan S; Weinstock, Nadav; Witelson, Sandra F; Sherwood, Chet C; Hof, Patrick R

2013-03-01

The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name "pararaphales" has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the "PRa" in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans.

The Neuroanatomy of the Reticular Nucleus Locus Coeruleus in Alzheimer’s Disease

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Giorgi, Filippo S.; Ryskalin, Larisa; Ruffoli, Riccardo; Biagioni, Francesca; Limanaqi, Fiona; Ferrucci, Michela; Busceti, Carla L.; Bonuccelli, Ubaldo; Fornai, Francesco

2017-01-01

Alzheimer’s Disease (AD) features the accumulation of β-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs), respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC), which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE) and it modulates a variety of functions including sleep-waking cycle, alertness, synaptic plasticity, and memory. The iso-dendritic nature of LC neurons allows their axons to spread NE throughout the whole forebrain. Likewise, a prion-like hypothesis suggests that Tau aggregates may travel along LC axons to reach out cortical neurons. Despite this timing is compatible with cross-sectional studies, there is no actual evidence for a causal relationship between these events. In the present mini-review, we dedicate special emphasis to those various mechanisms that may link degeneration of LC neurons to the onset of AD pathology. This includes the hypothesis that a damage to LC neurons contributes to the onset of dementia due to a loss of neuroprotective effects or, even the chance that, LC degenerates independently from cortical pathology. At the same time, since LC neurons are lost in a variety of neuropsychiatric disorders we considered which molecular mechanism may render these brainstem neurons so vulnerable. PMID:28974926
The Neuroanatomy of the Reticular Nucleus Locus Coeruleus in Alzheimer's Disease.

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Giorgi, Filippo S; Ryskalin, Larisa; Ruffoli, Riccardo; Biagioni, Francesca; Limanaqi, Fiona; Ferrucci, Michela; Busceti, Carla L; Bonuccelli, Ubaldo; Fornai, Francesco

2017-01-01

Alzheimer's Disease (AD) features the accumulation of β-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs), respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC), which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE) and it modulates a variety of functions including sleep-waking cycle, alertness, synaptic plasticity, and memory. The iso-dendritic nature of LC neurons allows their axons to spread NE throughout the whole forebrain. Likewise, a prion-like hypothesis suggests that Tau aggregates may travel along LC axons to reach out cortical neurons. Despite this timing is compatible with cross-sectional studies, there is no actual evidence for a causal relationship between these events. In the present mini-review, we dedicate special emphasis to those various mechanisms that may link degeneration of LC neurons to the onset of AD pathology. This includes the hypothesis that a damage to LC neurons contributes to the onset of dementia due to a loss of neuroprotective effects or, even the chance that, LC degenerates independently from cortical pathology. At the same time, since LC neurons are lost in a variety of neuropsychiatric disorders we considered which molecular mechanism may render these brainstem neurons so vulnerable.
The Neuroanatomy of the Reticular Nucleus Locus Coeruleus in Alzheimer’s Disease

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Filippo S. Giorgi

2017-09-01

Full Text Available Alzheimer’s Disease (AD features the accumulation of β-amyloid and Tau aggregates, which deposit as extracellular plaques and intracellular neurofibrillary tangles (NFTs, respectively. Neuronal Tau aggregates may appear early in life, in the absence of clinical symptoms. This occurs in the brainstem reticular formation and mostly within Locus Coeruleus (LC, which is consistently affected during AD. LC is the main source of forebrain norepinephrine (NE and it modulates a variety of functions including sleep-waking cycle, alertness, synaptic plasticity, and memory. The iso-dendritic nature of LC neurons allows their axons to spread NE throughout the whole forebrain. Likewise, a prion-like hypothesis suggests that Tau aggregates may travel along LC axons to reach out cortical neurons. Despite this timing is compatible with cross-sectional studies, there is no actual evidence for a causal relationship between these events. In the present mini-review, we dedicate special emphasis to those various mechanisms that may link degeneration of LC neurons to the onset of AD pathology. This includes the hypothesis that a damage to LC neurons contributes to the onset of dementia due to a loss of neuroprotective effects or, even the chance that, LC degenerates independently from cortical pathology. At the same time, since LC neurons are lost in a variety of neuropsychiatric disorders we considered which molecular mechanism may render these brainstem neurons so vulnerable.
Two oculomotor-related areas of the brainstem project to the dorsolateral periaqueductal gray.

NARCIS (Netherlands)

Klop, E.M.; Mouton, Leonora J.; Holstege, Gert

2005-01-01

The dorsolateral column of the periaqueductal gray (PAGdl) is usually associated with defensive behavior, but how this is brought about is not yet fully understood. In order to elucidate the function of PAGdl, its afferents from the brainstem were investigated in cats. Retrograde tracing results
Brainstem auditory evoked potentials in healthy cats recorded with surface electrodes

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Mihai Musteata

2013-01-01

Full Text Available The aim of this study was to evaluate the brainstem auditory evoked potentials of seven healthy cats, using surface electrodes. Latencies of waves I, III and V, and intervals I–III, I–V and III–V were recorded. Monaural and binaural stimulation of the cats were done with sounds ranging between 40 and 90 decibel Sound Pressure Level. All latencies were lower than those described in previous studies, where needle electrodes were used. In the case of binaural stimulation, latencies of waves III and V were greater compared to those obtained for monaural stimulation (P P > 0.05. Regardless of the sound intensity, the interwave latency was constant (P > 0.05. Interestingly, no differences were noticed for latencies of waves III and V when sound intensity was higher than 80dB SPL. This study completes the knowledge in the field of electrophysiology and shows that the brainstem auditory evoked potentials in cats using surface electrodes is a viable method to record the transmission of auditory information. That can be faithfully used in clinical practice, when small changes of latency values may be an objective factor in health status evaluation.
The analgesic agent tapentadol inhibits calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism.

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Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe

2016-01-15

In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake. Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K(+)-stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system. This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors. Copyright © 2015 Elsevier Inc. All rights reserved.
Organization of diencephalic and brainstem afferent projections to the lateral septum in the rat

NARCIS (Netherlands)

Luiten, Paul G.M.; Kuipers, Folkert; Schuitmaker, Hans

1982-01-01

Ascending diencephalic and brainstem afferents to the lateral septal column were studied by retrograde transport of horseradish peroxidase following microiontophoretic injections in the various subdivisions of the lateral septal area. Predominantly ispilateral cells, of which several coincide with
Descending Command Neurons in the Brainstem that Halt Locomotion

DEFF Research Database (Denmark)

Bouvier, Julien; Caggiano, Vittorio; Leiras, Roberto

2015-01-01

identifiable brainstem populations to a potential locomotor stop signal, we used developmental genetics and considered a discrete neuronal population in the reticular formation: the V2a neurons. We find that those neurons constitute a major excitatory pathway to locomotor areas of the ventral spinal cord....... Selective activation of V2a neurons of the rostral medulla stops ongoing locomotor activity, owing to an inhibition of premotor locomotor networks in the spinal cord. Moreover, inactivation of such neurons decreases spontaneous stopping in vivo. Therefore, the V2a "stop neurons" represent a glutamatergic...
Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy.

Science.gov (United States)

Ferris, Matthew J; Zhong, Jim; Switchenko, Jeffrey M; Higgins, Kristin A; Cassidy, Richard J; McDonald, Mark W; Eaton, Bree R; Patel, Kirtesh R; Steuer, Conor E; Baddour, H Michael; Miller, Andrew H; Bruner, Deborah W; Xiao, Canhua; Beitler, Jonathan J

2018-01-01

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients. At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed. Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores. In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue. Copyright © 2017 Elsevier B.V. All rights reserved.
Study of automated segmentation of the cerebellum and brainstem on brain MR images

International Nuclear Information System (INIS)

Hayashi, Norio; Matsuura, Yukihiro; Sanada, Shigeru; Suzuki, Masayuki

2005-01-01

MR imaging is an important method for diagnosing abnormalities of the brain. This paper presents an automated method to segment the cerebellum and brainstem for brain MR images. MR images were obtained from 10 normal subjects (male 4, female 6; 22-75 years old, average 31.0 years) and 15 patients with brain atrophy (male 3, female 12; 62-85 years of age, average 76.0 years). The automated method consisted of the following four steps: segmentation of the brain on original images, detection of an upper plane of the cerebellum using the Hough transform, correction of the plane using three-dimensional (3D) information, and segmentation of the cerebellum and brainstem using the plane. The results indicated that the regions obtained by the automated method were visually similar to those obtained by a manual method. The average rates of coincidence between the automated method and manual method were 83.0±9.0% in normal subjects and 86.4±3.6% in patients. (author)
Leucoencephalopathy with brainstem and spinal cord involvement and high lactate: quantitative magnetic resonance imaging

NARCIS (Netherlands)

Steenweg, M.E.; Pouwels, P.J.W.; Wolf, N.I.; van Wieringen, W.N.; Barkhof, F.; van der Knaap, M.S.

2011-01-01

Leucoencephalopathy with brainstem and spinal cord involvement and elevated lactate is a white matter disorder caused by DARS2 mutations. The pathology is unknown. We observed striking discrepancies between improvement on longitudinal conventional magnetic resonance images and clinical deterioration
Organization of the auditory brainstem in a lizard, Gekko gecko. I. Auditory nerve, cochlear nuclei, and superior olivary nuclei

DEFF Research Database (Denmark)

Tang, Y. Z.; Christensen-Dalsgaard, J.; Carr, C. E.

2012-01-01

We used tract tracing to reveal the connections of the auditory brainstem in the Tokay gecko (Gekko gecko). The auditory nerve has two divisions, a rostroventrally directed projection of mid- to high best-frequency fibers to the nucleus angularis (NA) and a more dorsal and caudal projection of lo...... of auditory connections in lizards and archosaurs but also different processing of low- and high-frequency information in the brainstem. J. Comp. Neurol. 520:17841799, 2012. (C) 2011 Wiley Periodicals, Inc...
Ablation of Ca(V2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

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Robert Theodor Mallmann

Full Text Available Voltage-gated Ca(V2.1 (P/Q-type Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V2.1 mouse models. Global Ca(V2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V2.1 in the adult murine forebrain.
An Evolutionarily Conserved Network Mediates Development of the zona limitans intrathalamica, a Sonic Hedgehog-Secreting Caudal Forebrain Signaling Center

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Elena Sena

2016-10-01

Full Text Available Recent studies revealed new insights into the development of a unique caudal forebrain-signaling center: the zona limitans intrathalamica (zli. The zli is the last brain signaling center to form and the first forebrain compartment to be established. It is the only part of the dorsal neural tube expressing the morphogen Sonic Hedgehog (Shh whose activity participates in the survival, growth and patterning of neuronal progenitor subpopulations within the thalamic complex. Here, we review the gene regulatory network of transcription factors and cis-regulatory elements that underlies formation of a shh-expressing delimitated domain in the anterior brain. We discuss evidence that this network predates the origin of chordates. We highlight the contribution of Shh, Wnt and Notch signaling to zli development and discuss implications for the fact that the morphogen Shh relies on primary cilia for signal transduction. The network that underlies zli development also contributes to thalamus induction, and to its patterning once the zli has been set up. We present an overview of the brain malformations possibly associated with developmental defects in this gene regulatory network (GRN.
Brainstem and limbic encephalitis with paraneoplastic neuromyelitis optica.

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Moussawi, Khaled; Lin, David J; Matiello, Marcelo; Chew, Sheena; Morganstern, Daniel; Vaitkevicius, Henrikas

2016-01-01

The spectrum of disorders associated with anti-neuromyelitis optica (NMO) antibody is being extended to include infrequent instances associated with cancer. We describe a patient with brainstem and limbic encephalitis from NMO-immunoglobulin G in serum and cerebrospinal fluid in the context of newly diagnosed breast cancer. The neurological features markedly improved with excision of her breast cancer and immune suppressive therapy. This case further broadens the NMO spectrum disorders (NMOSD) by an association between NMOSD and cancer and raises the question of coincidental occurrence and the appropriate circumstances to search for a tumor in certain instances of NMO. Copyright © 2015 Elsevier Ltd. All rights reserved.
Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration

DEFF Research Database (Denmark)

Hébert, Sébastien S; Papadopoulou, Aikaterini S; Smith, Pascal

2010-01-01

, particularly in the adult brain, remain poorly defined. Here we show that the absence of Dicer in the adult forebrain is accompanied by a mixed neurodegenerative phenotype. Although neuronal loss is observed in the hippocampus, cellular shrinkage is predominant in the cortex. Interestingly, neuronal...... degeneration coincides with the hyperphosphorylation of endogenous tau at several epitopes previously associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 as one of the candidate kinases responsible for this event in vivo. We further...
Brain Tumor Therapy-Induced Changes in Normal-Appearing Brainstem Measured With Longitudinal Diffusion Tensor Imaging

International Nuclear Information System (INIS)

Hua Chiaho; Merchant, Thomas E.; Gajjar, Amar; Broniscer, Alberto; Zhang, Yong; Li Yimei; Glenn, George R.; Kun, Larry E.; Ogg, Robert J.

2012-01-01

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4–39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54–59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6–5.0 years). The median mean dose to the pons was 56 Gy (range, 7–59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response
Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura.

Science.gov (United States)

Hougaard, Anders; Amin, Faisal M; Christensen, Casper E; Younis, Samaira; Wolfram, Frauke; Cramer, Stig P; Larsson, Henrik B W; Ashina, Messoud

2017-06-01

See Moskowitz (doi:10.1093/brain/awx099) for a scientific commentary on this article.The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier
Heart rate variability and QT dispersion study in brain death patients and comatose patients with normal brainstem function

International Nuclear Information System (INIS)

Vakilian, A.R.; Iranmanesh, F.; Nadimi, A.E.; Kahnali, J.A.

2011-01-01

To compare heart rate variability (HRV) and QT dispersion in comatose patients with normal brainstem function and with brain death. Fourteen brain death patients with clinical signs of imminent brain death and 15 comatose patients were examined by neurologist in intensive care unit. HRV, RR interval and QT dispersion on ECG were assessed for 24 hours in both groups. Independent t-test and chi-square test were used for statistical analysis to determine significance which was set at p < 0.05. According to Holter findings, mean of standard deviation of RR-interval in the comatose and brain death groups was 48.33 and 35 respectively (p = 0.045). Mean of covariance coefficient of RR-interval was 0.065 in the comatose group and 0.043 in the brain deaths (p = 0.006). QT dispersion was not significant difference in two groups. HRV and RR-interval analysis appeared as an early finding for the diagnosis of brainstem death in comparison to comatose patients with normal brainstem function. QT dispersion had not significant in this regard. (author)
Sensitization of trigeminal brainstem pathways in a model for tear deficient dry eye.

Science.gov (United States)

Rahman, Mostafeezur; Okamoto, Keiichiro; Thompson, Randall; Katagiri, Ayano; Bereiter, David A

2015-05-01

Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. Ocular-responsive neurons were recorded at the interpolaris/caudalis transition (Vi/Vc) and Vc/upper cervical cord (Vc/C1) regions under isoflurane, whereas OOemg activity was recorded under urethane. Spontaneous tear volume was reduced by ∼50% at 14 days after exorbital gland removal. Hypertonic saline-evoked eye blink behavior in awake rats was enhanced throughout the 14 days after surgery. Saline-evoked neural activity at the Vi/Vc transition and in superficial and deep laminae at the Vc/C1 region was greatly enhanced in DE rats. Neurons from DE rats classified as wide dynamic range displayed enlarged convergent periorbital receptive fields consistent with central sensitization. Saline-evoked OOemg activity was markedly enhanced in DE rats compared with controls. Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline-evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation.

Speech auditory brainstem response (speech ABR) characteristics depending on recording conditions, and hearing status: an experimental parametric study.

Science.gov (United States)

Akhoun, Idrick; Moulin, Annie; Jeanvoine, Arnaud; Ménard, Mikael; Buret, François; Vollaire, Christian; Scorretti, Riccardo; Veuillet, Evelyne; Berger-Vachon, Christian; Collet, Lionel; Thai-Van, Hung

2008-11-15

Speech elicited auditory brainstem responses (Speech ABR) have been shown to be an objective measurement of speech processing in the brainstem. Given the simultaneous stimulation and recording, and the similarities between the recording and the speech stimulus envelope, there is a great risk of artefactual recordings. This study sought to systematically investigate the source of artefactual contamination in Speech ABR response. In a first part, we measured the sound level thresholds over which artefactual responses were obtained, for different types of transducers and experimental setup parameters. A watermelon model was used to model the human head susceptibility to electromagnetic artefact. It was found that impedances between the electrodes had a great effect on electromagnetic susceptibility and that the most prominent artefact is due to the transducer's electromagnetic leakage. The only artefact-free condition was obtained with insert-earphones shielded in a Faraday cage linked to common ground. In a second part of the study, using the previously defined artefact-free condition, we recorded speech ABR in unilateral deaf subjects and bilateral normal hearing subjects. In an additional control condition, Speech ABR was recorded with the insert-earphones used to deliver the stimulation, unplugged from the ears, so that the subjects did not perceive the stimulus. No responses were obtained from the deaf ear of unilaterally hearing impaired subjects, nor in the insert-out-of-the-ear condition in all the subjects, showing that Speech ABR reflects the functioning of the auditory pathways.
Auditory brainstem response as a diagnostic tool for patients suffering from schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder: protocol.

Science.gov (United States)

Wahlström, Viktor; Åhlander, Fredrik; Wynn, Rolf

2015-02-12

Psychiatric disorders, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and bipolar disorder, may sometimes be difficult to diagnose. There is a great need for a valid and reliable diagnostic tool to aid clinicians in arriving at the diagnoses in a timely and accurate manner. Prior studies have suggested that patients suffering from schizophrenia and ADHD may process certain sound stimuli in the brainstem in an unusual manner. When these patient groups have been examined with the electrophysiological method of brainstem audiometry, some studies have found illness-specific aberrations. Such aberrations may also exist for patients suffering from bipolar disorder. In this study, we will examine whether the method of brainstem audiometry can be used as a diagnostic tool for patients suffering from schizophrenia, ADHD, and bipolar disorder. The method includes three steps: (1) auditory stimulation with specific sound stimuli, (2) simultaneous measurement of brainstem activity, and (3) automated interpretation of the resulting brain stem audiograms with data-based signal analysis. We will compare three groups of 12 individuals with confirmed diagnoses of schizophrenia, ADHD, or bipolar disorder with 12 healthy subjects under blinded conditions for a total of 48 participants. The extent to which the method can be used to reach the correct diagnosis will be investigated. The project is now in a recruiting phase. When all patients and controls have been recruited and the measurements have been performed, the data will be analyzed according to a previously arranged algorithm. We expect the recruiting phase and measurements to be completed in early 2015, the analyses to be performed in mid-2015, and the results of the study to be published in early 2016. If the results support previous findings, this will lend strength to the idea that brainstem audiometry can offer objective diagnostic support for patients suffering from schizophrenia, ADHD, and
Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer's Disease.

Science.gov (United States)

Kwakowsky, Andrea; Milne, Michael R; Waldvogel, Henry J; Faull, Richard L

2016-12-17

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer's disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer's disease.
Automatic hearing loss detection system based on auditory brainstem response

International Nuclear Information System (INIS)

Aldonate, J; Mercuri, C; Reta, J; Biurrun, J; Bonell, C; Gentiletti, G; Escobar, S; Acevedo, R

2007-01-01

Hearing loss is one of the pathologies with the highest prevalence in newborns. If it is not detected in time, it can affect the nervous system and cause problems in speech, language and cognitive development. The recommended methods for early detection are based on otoacoustic emissions (OAE) and/or auditory brainstem response (ABR). In this work, the design and implementation of an automated system based on ABR to detect hearing loss in newborns is presented. Preliminary evaluation in adults was satisfactory
Study of the correlation of brainstem auditory evoked potentials and magnetic resonance imaging in children with spastic cerebral palsy

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Fobe, Lisete Pessoa de Oliveira

1999-01-01

Central auditory evaluation in 21 children with cerebral palsy was done with brainstem auditory evoked potentials (BAEP) and correlated with brain magnetic resonance imaging findings (MRI); 12 boys and 9 girls between 5 and 12 years old were studied. All children had follow-up at the Institute of Orthopedics and Traumatology of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. The control group was done with 17 children, 10 boys and 7 girls (mean age 8.06 years, SD 2.27 years). The BAEP abnormalities were: decrease of latency of wave V; decrease of latency III-V and I-IV intervals at the right side. All patients has MRI supratentorial abnormalities and 11 had brainstem atrophy. The MRI pathologic findings were: ventricular enlargement (n=17 or 80.95%), cortical/subcortical atrophy (n=15 or 71.42%), left brainstem atrophy (n=11 or 52.38%), periventricular leukomalacia (n=10 or 47.61%), infarction in the left middle cerebral artery territory (n=6 or 28.57%), and malformations such as schizencephaly and colpocephaly (n=5 or 23.80%). The findings of the decrease latencies in children with cerebral palsy suggest the contribution of decussating auditory fibers at the lower and upper pons and midbrain, the lack of homogeneity of the surrounding volume of the conductor fibres and the presence of several concurrently active potential generators sources, should be facilitating mechanisms for the nervous input to brainstem. (author)
Study of the correlation of brainstem auditory evoked potentials and magnetic resonance imaging in children with spastic cerebral palsy

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Fobe, Lisete Pessoa de Oliveira [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina]. E-mail: lispessoa@yahoo.com

1999-12-01

Central auditory evaluation in 21 children with cerebral palsy was done with brainstem auditory evoked potentials (BAEP) and correlated with brain magnetic resonance imaging findings (MRI); 12 boys and 9 girls between 5 and 12 years old were studied. All children had follow-up at the Institute of Orthopedics and Traumatology of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. The control group was done with 17 children, 10 boys and 7 girls (mean age 8.06 years, SD 2.27 years). The BAEP abnormalities were: decrease of latency of wave V; decrease of latency III-V and I-IV intervals at the right side. All patients has MRI supratentorial abnormalities and 11 had brainstem atrophy. The MRI pathologic findings were: ventricular enlargement (n=17 or 80.95%), cortical/subcortical atrophy (n=15 or 71.42%), left brainstem atrophy (n=11 or 52.38%), periventricular leukomalacia (n=10 or 47.61%), infarction in the left middle cerebral artery territory (n=6 or 28.57%), and malformations such as schizencephaly and colpocephaly (n=5 or 23.80%). The findings of the decrease latencies in children with cerebral palsy suggest the contribution of decussating auditory fibers at the lower and upper pons and midbrain, the lack of homogeneity of the surrounding volume of the conductor fibres and the presence of several concurrently active potential generators sources, should be facilitating mechanisms for the nervous input to brainstem. (author)
Dose Sparing of Brainstem and Spinal Cord for Re-Irradiating Recurrent Head and Neck Cancer with Intensity-Modulated Radiotherapy

International Nuclear Information System (INIS)

Chen, Chin-Cheng; Lee, Chen-Chiao; Mah, Dennis; Sharma, Rajiv; Landau, Evan; Garg, Madhur; Wu, Andrew

2011-01-01

Because of the dose limit for critical structures such as brainstem and spinal cord, administering a dose of 60 Gy to patients with recurrent head and neck cancer is challenging for those who received a previous dose of 60-70 Gy. Specifically, previously irradiated head and neck patients may have received doses close to the tolerance limit to their brainstem and spinal cord. In this study, a reproducible intensity-modulated radiation therapy (IMRT) treatment design is presented to spare the doses to brainstem and spinal cord, with no compromise of prescribed dose delivery. Between July and November 2008, 7 patients with previously irradiated, recurrent head and neck cancers were treated with IMRT. The jaws of each field were set fixed with the goal of shielding the brainstem and spinal cord at the sacrifice of partial coverage of the planning target volume (PTV) from any particular beam orientation. Beam geometry was arranged to have sufficient coverage of the PTV and ensure that the constraints of spinal cord o , patients could be treated by 18 fields. Six patients met these criteria and were treated in 25 minutes per fraction. One patient exceeded a 30 o Cobb's angle and was treated by 31 fields in 45 minutes per fraction. We have demonstrated a new technique for retreatment of head and neck cancers. The angle of cervical spine curvature plays an important role in the efficiency and effectiveness of our approach.
Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus.

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McAlpine, D; Jiang, D; Shackleton, T M; Palmer, A R

1998-08-01

Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidence-detector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors.
Immediate, irreversible, posttraumatic coma: a review indicating that bilateral brainstem injury rather than widespread hemispheric damage is essential for its production.

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Rosenblum, William I

2015-03-01

Traumatic brain injury may result in immediate long-lasting coma. Much attention has been given to predicting this outcome from the initial examination because these predictions can guide future treatment and interactions with the patient's family. Reports of diffuse axonal injury in these cases have ascribed the coma to widespread damage in the deep white matter that disconnects the hemispheres from the ascending arousal system (AAS). However, brainstem lesions are also present in such cases, and the AAS may be interrupted at the brainstem level. This review examines autopsy and imaging literature that assesses the presence, extent, and predictive value of lesions in both sites. The evidence suggests that diffuse injury to the deep white matter is not the usual cause of immediate long-lasting posttraumatic coma. Instead, brainstem lesions in the rostral pons or midbrain are almost always the cause but only if the lesions are bilateral. Moreover, recovery is possible if critical brainstem inputs to the AAS are spared. The precise localization of the latter is subject to ongoing investigation with advanced imaging techniques using magnets of very high magnetic gradients. Limited availability of this equipment plus the need to verify the findings continue to require meticulous autopsy examination.
Herpes simplex encephalitis with thalamic, brainstem and cerebellar involvement.

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Garg, Meenal; Kulkarni, Shilpa; Udwadia Hegde, Anaita

2018-04-01

Herpes simplex virus encephalitis is a common and treatable cause of acute encephalitis in all age groups. Certain radiological features such as temporal parenchymal involvement facilitate the diagnosis. The use of herpes simplex virus polymerase chain reaction has expanded the clinical and imaging spectrum. We report the case of a young patient who presented with a movement disorder and predominant involvement of thalami, brainstem and cerebellum on magnetic resonance imaging, and was diagnosed with herpes simplex virus encephalitis. Differentiation from Japanese encephalitis may be difficult in these patients, especially in endemic areas, and may necessitate the use of relevant investigations in all patients.
Whole-Brain Monosynaptic Afferent Inputs to Basal Forebrain Cholinergic System

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Rongfeng Hu

2016-10-01

Full Text Available The basal forebrain cholinergic system (BFCS robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum (LS, central amygdala (CeA, paraventricular nucleus of hypothalamus (PVH, dorsal raphe (DRN and parabrachial nucleus (PBN. Interestingly, we found that the BFCS receives inputs from the olfactory areas and the entorhinal-hippocampal system. These results greatly expand our knowledge about the connectivity of the mouse BFCS and provided important preliminary indications for future exploration of circuit function.
Abnormal Auditory Brainstem Response (ABR Findings in a Near-Normal Hearing Child with Noonan Syndrome

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Bahram Jalaei

2017-01-01

Full Text Available Introduction: Noonan syndrome (NS is a heterogeneous genetic disease that affects many parts of the body. It was named after Dr. Jacqueline Anne Noonan, a paediatric cardiologist.Case Report: We report audiological tests and auditory brainstem response (ABR findings in a 5-year old Malay boy with NS. Despite showing the marked signs of NS, the child could only produce a few meaningful words. Audiological tests found him to have bilateral mild conductive hearing loss at low frequencies. In ABR testing, despite having good waveform morphology, the results were atypical. Absolute latency of wave V was normal but interpeak latencies of wave’s I-V, I-II, II-III were prolonged. Interestingly, interpeak latency of waves III-V was abnormally shorter.Conclusion:Abnormal ABR results are possibly due to abnormal anatomical condition of brainstem and might contribute to speech delay.
Erythropoietin and its receptors in the brainstem of adults with fatal falciparum malaria

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White Nicholas J

2009-11-01

Full Text Available Abstract Background Facilitation of endogenous neuroprotective pathways, such as the erythropoietin (Epo pathway, has been proposed as adjuvant treatment strategies in cerebral malaria. Whether different endogenous protein expression levels of Epo or differences in the abundance of its receptor components could account for the extent of structural neuropathological changes or neurological complications in adults with severe malaria was investigated. Methods High sensitivity immunohistochemistry was used to assess the frequency, distribution and concordance of Epo and components of its homodimeric and heteromeric receptors, Epo receptor and CD131, within the brainstem of adults who died of severe malaria. The following relationships with Epo and its receptor components were also defined: (i sequestration and indicators of hypoxia; (ii vascular damage in the form of plasma protein leakage and haemorrhage; (iii clinical complications and neuropathological features of severe malaria disease. Brainstems of patients dying in the UK from unrelated non-infectious causes were examined for comparison. Results The incidence of endogenous Epo in parenchymal brain cells did not greatly differ between severe malaria and non-neurological UK controls at the time of death. However, EpoR and CD131 labelling of neurons was greater in severe malaria compared with non-neurological controls (P = .009. EpoR labelling of vessels was positively correlated with admission peripheral parasite count (P = .01 and cerebral sequestration (P P = .001. There were no significant correlations with indicators of vascular damage, neuronal chromatolysis, axonal swelling or vital organ failure. Conclusion Cells within the brainstem of severe malaria patients showed protein expression of Epo and its receptor components. However, the incidence of endogeneous expression did not reflect protection from vascular or neuronal injury, and/or clinical manifestations, such as coma. These
Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

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Sariñana, Joshua; Tonegawa, Susumu

2017-01-01

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222
Auditory Brainstem Response to Complex Sounds Predicts Self-Reported Speech-in-Noise Performance

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Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

2013-01-01

Purpose: To compare the ability of the auditory brainstem response to complex sounds (cABR) to predict subjective ratings of speech understanding in noise on the Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse & Noble, 2004) relative to the predictive ability of the Quick Speech-in-Noise test (QuickSIN; Killion, Niquette,…
Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.

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Pivetta, Chiara; Esposito, Maria Soledad; Sigrist, Markus; Arber, Silvia

2014-01-30

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement. Copyright © 2014 Elsevier Inc. All rights reserved.
Difficult diagnosis of brainstem glioblastoma multiforme in a woman: a case report and review of the literature

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Lakhan Shaheen E

2009-10-01

Full Text Available Abstract Introduction Brainstem gliomas are rare in adults. They most commonly occur in the pons and are most likely to be high-grade lesions. The diagnosis of a high-grade brainstem glioma is usually reached due to the presentation of rapidly progressing brainstem, cranial nerve and cerebellar symptoms. These symptoms do, however, overlap with a variety of other central nervous system disorders. Magnetic resonance imaging is the radiographic modality of choice, but can still be misleading. Case presentation A 48-year-old Caucasian woman presented with headache and vomiting followed by cerebellar signs and confusion. Magnetic resonance imaging findings were suggestive of a demyelinating process, but the patient failed to respond to therapy. Her condition rapidly progressed and she died. At autopsy, a high-grade invasive pontine tumor was identified. Histological evaluation revealed glioblastoma multiforme. Conclusion While pontine gliomas are rare in adults, those that do occur tend to be high-grade and rapidly progressive. Progression of symptoms from non-specific findings of headache and vomiting to rapid neurological deterioration, as occurred in our patient, is common in glioblastoma multiforme. While radiographic findings are often suggestive of the underlying pathology, this case represents the possibility of glioblastoma multiforme presenting as a deceptively benign appearing lesion.
Neuropeptide Y in the olfactory system, forebrain and pituitary of the teleost, Clarias batrachus.

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Gaikwad, Archana; Biju, K C; Saha, Subhash G; Subhedar, Nishikant

2004-03-01

Distribution of neuropeptide Y (NPY)-like immunoreactivity in the forebrain of catfish Clarias batrachus was examined with immunocytochemistry. Conspicuous immunoreactivity was seen in the olfactory receptor neurons (ORNs), their projections in the olfactory nerve, fascicles of the olfactory nerve layer in the periphery of bulb and in the medial olfactory tracts as they extend to the telencephalic lobes. Ablation of the olfactory organ resulted in loss of immunoreactivity in the olfactory nerve layer of the bulb and also in the fascicles of the medial olfactory tracts. This evidence suggests that NPY may serve as a neurotransmitter in the ORNs and convey chemosensory information to the olfactory bulb, and also to the telencephalon over the extrabulbar projections. In addition, network of beaded immunoreactive fibers was noticed throughout the olfactory bulb, which did not respond to ablation experiment. These fibers may represent centrifugal innervation of the bulb. Strong immunoreactivity was encountered in some ganglion cells of nervus terminalis. Immunoreactive fibers and terminal fields were widely distributed in the telencephalon. Several neurons of nucleus entopeduncularis were moderately immunoreactive; and a small population of neurons in nucleus preopticus periventricularis was also labeled. Immunoreactive terminal fields were particularly conspicuous in the preoptic, the tuberal areas, and the periventricular zone around the third ventricle and inferior lobes. NPY immunoreactive cells and fibers were detected in all the lobes of the pituitary gland. Present results describing the localization of NPY in the forebrain of C. batrachus are in concurrence with the pattern of the immunoreactivity encountered in other teleosts. However, NPY in olfactory system of C. batrachus is a novel feature that suggests a role for the peptide in processing of chemosensory information.
Speech-evoked auditory brainstem responses in children with hearing loss.

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Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine

2017-08-01

The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.
Cortical cholinergic hypofunction and behaviorial impairment produced by basal forebrain lesions in the rat

International Nuclear Information System (INIS)

Lerer, B.E.; Friedman, E.; Gamzu, E.

1986-01-01

The authors confirm the cortical ChAT and passive avoidance deficits resulting from bilateral KA lesions of the magnocellular nuclei of the basal forebrain (MNBF). Because of reported passive avoidance deficits, the authors were interested in whether bilateral MNBF lesions would interfere with learning in an active avoidance paradigm. Samples of rat cortex were stored at -80 C until assayed. ChAT was assayed by a modification method under saturating conditions; 20 mM choline and 2 mM C 14-acetylcoenzyme. The behavioral deficits assumed to be indicative of learning and memory problems were accompanied by a 20% decrease in cortical ChAT

Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

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Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

1998-01-01

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.
Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

Science.gov (United States)

Kwakowsky, Andrea; Milne, Michael R.; Waldvogel, Henry J.; Faull, Richard L.

2016-01-01

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease. PMID:27999310
Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

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Andrea Kwakowsky

2016-12-01

Full Text Available The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2 on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease.
Effects of brainstem lesions on the masseter inhibitory reflex. Functional mechanisms of reflex pathways

NARCIS (Netherlands)

Ongerboer de Visser, B. W.; Cruccu, G.; Manfredi, M.; Koelman, J. H.

1990-01-01

The masseter inhibitory reflex (MIR) was investigated in 16 patients with localized brainstem lesions involving the trigeminal system. The MIR consists of two phases of EMG silence (S1 and S2) evoked by stimulation of the mental nerve during maximal clenching of the teeth. The extent of the lesions
Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study.

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McNamara, Robert K; Schurdak, Jennifer D; Asch, Ruth H; Peters, Bart D; Lindquist, Diana M

2018-01-01

Neuropsychiatric disorders that frequently initially emerge during adolescence are associated with deficits in the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA), elevated proinflammatory signaling, and regional reductions in white matter integrity (WMI). This study determined the effects of altering brain DHA accrual during adolescence on WMI in the rat brain by diffusion tensor imaging (DTI), and investigated the potential mediating role of proinflammatory signaling. During periadolescent development, male rats were fed a diet deficient in n-3 fatty acids (DEF, n = 20), a fish oil-fortified diet containing preformed DHA (FO, n = 20), or a control diet (CON, n = 20). In adulthood, DTI scans were performed and brain WMI was determined using voxelwise tract-based spatial statistics (TBSS). Postmortem fatty acid composition, peripheral (plasma IL-1β, IL-6, and C-reactive protein [CRP]) and central (IL-1β and CD11b mRNA) proinflammatory markers, and myelin basic protein (MBP) mRNA expression were determined. Compared with CON rats, forebrain DHA levels were lower in DEF rats and higher in FO rats. Compared with CON rats, DEF rats exhibited greater radial diffusivity (RD) and mean diffusivity in the right external capsule, and greater axial diffusivity in the corpus callosum genu and left external capsule. DEF rats also exhibited greater RD than FO rats in the right external capsule. Forebrain MBP expression did not differ between groups. Compared with CON rats, central (IL-1β and CD11b) and peripheral (IL-1β and IL-6) proinflammatory markers were not different in DEF rats, and DEF rats exhibited lower CRP levels. These findings demonstrate that deficits in adolescent DHA accrual negatively impact forebrain WMI, independently of elevated proinflammatory signaling. © 2017 S. Karger AG, Basel.
DESCRIPTION OF BRAINSTEM AUDITORY EVOKED RESPONSES (AIR AND BONE CONDUCTION IN CHILDREN WITH NORMAL HEARING

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A. V. Pashkov

2014-01-01

Full Text Available Diagnosis of hearing level in small children with conductive hearing loss associated with congenital craniofacial abnormalities, particularly with agenesis of external ear and external auditory meatus is a pressing issue. Conventional methods of assessing hearing in the first years of life, i. e. registration of brainstem auditory evoked responses to acoustic stimuli in the event of air conduction, does not give an indication of the auditory analyzer’s condition due to potential conductive hearing loss in these patients. This study was aimed at assessing potential of diagnosing the auditory analyzer’s function with registering brainstem auditory evoked responses (BAERs to acoustic stimuli transmitted by means of a bone vibrator. The study involved 17 children aged 3–10 years with normal hearing. We compared parameters of registering brainstem auditory evoked responses (peak V depending on the type of stimulus transmission (air/bone in children with normal hearing. The data on thresholds of the BAERs registered to acoustic stimuli in the event of air and bone conduction obtained in this study are comparable; hearing thresholds in the event of acoustic stimulation by means of a bone vibrator correlates with the results of the BAERs registered to the stimuli transmitted by means of air conduction earphones (r = 0.9. High correlation of thresholds of BAERs to the stimuli transmitted by means of a bone vibrator with thresholds of BAERs registered when air conduction earphones were used helps to assess auditory analyzer’s condition in patients with any form of conductive hearing loss.
Physiological and Morphological Characterization of Organotypic Cocultures of the Chick Forebrain Area MNH and its Main Input Area DMA/DMP

OpenAIRE

Endepols, Heike; Jungnickel, Julia; Braun, Katharina

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostrai neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were lightand electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic syn...
Left-right asymmetry of maturation rates in human embryonic neural development

OpenAIRE

De Kovel, C.; Lisgo, S.; Karlebach, G.; Ju, J.; Cheng, G.; Fisher, S.; Francks, C.

2017-01-01

Background Left-right asymmetry is a fundamental organizing feature of the human brain, and neuro-psychiatric disorders such as schizophrenia sometimes involve alterations of brain asymmetry. As early as 8 weeks post conception, the majority of human fetuses move their right arms more than their left arms, but because nerve fibre tracts are still descending from the forebrain at this stage, spinal-muscular asymmetries are likely to play an important developmental role. Methods We used RNA seq...
SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism

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Ozair, Mohammad Zeeshan; Noggle, Scott; Warmflash, Aryeh; Krzyspiak, Joanna Ela; Brivanlou, Ali H.

2013-01-01

Human embryonic stem cells (hESCs) provide a valuable window into the dissection of the molecular circuitry underlying the early formation of the human forebrain. However, dissection of signaling events in forebrain development using current protocols is complicated by non-neural contamination and fluctuation of extrinsic influences. Here we show that SMAD7, a cell-intrinsic inhibitor of TGFβ signaling, is sufficient to directly convert pluripotent hESCs to an anterior neural fate. Time-course gene expression revealed down-regulation of MAPK components, and combining MEK1/2 inhibition with SMAD7-mediated TGFβ inhibition promoted telencephalic conversion. FGF-MEK and TGFβ-SMAD signaling maintain hESCs by promoting pluripotency genes and repressing neural genes. Our findings suggest that in the absence of these cues, pluripotent cells simply revert to a program of neural conversion. Hence the “primed” state of hESCs requires inhibition of the “default” state of neural fate acquisition. This has parallels in amphibians, suggesting an evolutionarily conserved mechanism. PMID:23034881
Multi-tensor investigation of orbitofrontal cortex tracts affected in subcaudate tractotomy.

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Yang, Jimmy C; Papadimitriou, George; Eckbo, Ryan; Yeterian, Edward H; Liang, Lichen; Dougherty, Darin D; Bouix, Sylvain; Rathi, Yogesh; Shenton, Martha; Kubicki, Marek; Eskandar, Emad N; Makris, Nikos

2015-06-01

Subcaudate tractotomy (SCT) is a neurosurgical lesioning procedure that can reduce symptoms in medically intractable obsessive compulsive disorder (OCD). Due to the putative importance of the orbitofrontal cortex (OFC) in symptomatology, fibers that connect the OFC, SCT lesion, and either the thalamus or brainstem were investigated with two-tensor tractography using an unscented Kalman filter approach. From this dataset, fibers were warped to Montreal Neurological Institute space, and probability maps with center-of-mass analysis were subsequently generated. In comparing fibers from the same OFC region, including medial OFC (mOFC), central OFC (cOFC), and lateral OFC (lOFC), the area of divergence for fibers connected with the thalamus versus the brainstem is posterior to the anterior commissure. At the anterior commissure, fibers connected with the thalamus run dorsal to those connected with the brainstem. As OFC fibers travel through the ventral aspect of the internal capsule, lOFC fibers are dorsal to cOFC and mOFC fibers. Using neuroanatomical comparison, tracts coursing between the OFC and thalamus are likely part of the anterior thalamic radiations, while those between the OFC and brainstem likely belong to the medial forebrain bundle. These data support the involvement of the OFC in OCD and may be relevant to creating differential lesional procedures of specific tracts or to developing deep brain stimulation programming paradigms.
Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

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Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

2013-09-05

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.
Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

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Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

2016-01-01

Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.
Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber.

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Nikodemus Gessele

Full Text Available Naked mole-rats (Heterocephalus glaber live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.
Cerebrovascular endothelin-1 hyper-reactivity is associated with transient receptor potential canonical channels 1 and 6 activation and delayed cerebral hypoperfusion after forebrain ischaemia in rats

DEFF Research Database (Denmark)

Johansson, S E; Andersen, X E D R; Hansen, R H

2015-01-01

. METHODS: Experimental forebrain ischaemia was induced in Wistar male rats by a two-vessel occlusion model, and the cerebral blood flow was measured by magnetic resonance imaging two days after reperfusion. In vitro vasoreactivity studies, immunofluorescence and quantitative PCR were performed on cerebral...... in the vascular smooth muscle cells was enhanced and correlated with decreased cerebral blood flow two days after forebrain ischaemia. Furthermore, under conditions when voltage-dependent calcium channels were inhibited, endothelin-1-induced cerebrovascular contraction was enhanced and this enhancement...... was presumably mediated by Ca(2+) influx via upregulated transient receptor potential canonical channels 1 and 6. CONCLUSIONS: Our data demonstrates that endothelin-1-mediated influx of extracellular Ca(2+) activates transient receptor potential canonical channels 1 and 6 in cerebral vascular smooth muscle cells...
Correlation of augmented startle reflex with brainstem electrophysiological responses in Tay-Sachs disease.

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Nakamura, Sadao; Saito, Yoshiaki; Ishiyama, Akihiko; Sugai, Kenji; Iso, Takashi; Inagaki, Masumi; Sasaki, Masayuki

2015-01-01

To clarify the evolution of an augmented startle reflex in Tay-Sachs disease and compare the temporal relationship between this reflex and brainstem evoked potentials. Clinical and electrophysiological data from 3 patients with Tay-Sachs disease were retrospectively collected. The augmented startle reflex appeared between the age of 3 and 17 months and disappeared between the age of 4 and 6 years. Analysis of brainstem auditory evoked potentials revealed that poor segregation of peak I, but not peak III, coincided with the disappearance of the augmented startle reflex. A blink reflex with markedly high amplitude was observed in a patient with an augmented startle reflex. The correlation between the augmented startle reflex and the preservation of peak I but not peak III supports the theory that the superior olivary nucleus is dispensable for this reflex. The blink reflex with high amplitudes may represent augmented excitability of reticular formation at the pontine tegmentum in Tay-Sachs disease, where the pattern generators for the augmented startle and blink reflexes may functionally overlap. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Inflammatory lesions of the brainstem and the cerebellopontine angle; Entzuendungen des Hirnstamms und des Kleinhirnbrueckenwinkels

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Lutz, J.; Jaeger, L. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen (Germany). Institut fuer Klinische Radiologie

2006-03-15

Inflammatory lesions of the brainstem and the cerebellopontine angle are often critical for the patient, because crucial neuronal and vascular structures are found in this region. The patient's prognosis mainly depends on rapid identification of the inflammation site and the radiological evaluation of the inflammation pathogenesis to develop therapeutic strategies. Therefore, cross-sectional imaging is complementary to laboratory and CSF analysis as well as biopsies. This article gives a survey of inflammatory lesions of the brainstem and the cerebellopontine angle. (orig.) [German] Entzuendliche Erkrankungen des Hirnstamms und Kleinhirnbrueckenwinkels stellen nicht selten eine kritische Situation fuer den Patienten dar, da in diesen Regionen wichtige neuronale Strukturen und Gefaesse verlaufen. Die Prognose und das weitere therapeutische Vorgehen haengen entscheidend von einer schnellen Diagnose der Entzuendungslokalisation sowie einer bildmorphologischen Einordnung der Entzuendungspathogenese ab. Folglich ergaenzt die Schnittbildgebung entscheidend die Liquoranalyse, die Biopsie und die Laboruntersuchungen. In diesem Artikel soll eine Uebersicht ueber die verschiedenen entzuendlichen Veraenderungen des Hirnstamms und Kleinhirnbrueckenwinkels gegeben werden. (orig.)
Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience.

Science.gov (United States)

Kelly, Paul J; Lin, Yijie Brittany; Yu, Alvin Y C; Ropper, Alexander E; Nguyen, Paul L; Marcus, Karen J; Hacker, Fred L; Weiss, Stephanie E

2011-09-01

To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.
A frontal cortex event-related potential driven by the basal forebrain

Science.gov (United States)

Nguyen, David P; Lin, Shih-Chieh

2014-01-01

Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497
Calcium imaging of basal forebrain activity during innate and learned behaviors

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Thomas Clarke Harrison

2016-05-01

Full Text Available The basal forebrain (BF plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate or performed a go/no-go auditory discrimination task (learned. Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors.
Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at cortico-lateral amygdala synaptic connections.

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Veronica Bianchi

Full Text Available The GDI1 gene encodes αGDI, which retrieves inactive GDP-bound RAB from membranes to form a cytosolic pool awaiting vesicular release. Mutations in GDI1 are responsible for X-linked Intellectual Disability. Characterization of the Gdi1-null mice has revealed alterations in the total number and distribution of hippocampal and cortical synaptic vesicles, hippocampal short-term synaptic plasticity and specific short-term memory deficits in adult mice, which are possibly caused by alterations of different synaptic vesicle recycling pathways controlled by several RAB GTPases. However, interpretation of these studies is complicated by the complete ablation of Gdi1 in all cells in the brain throughout development. In this study, we generated conditionally gene-targeted mice in which the knockout of Gdi1 is restricted to the forebrain, hippocampus, cortex and amygdala and occurs only during postnatal development. Adult mutant mice reproduce the short-term memory deficit previously reported in Gdi1-null mice. Surprisingly, the delayed ablation of Gdi1 worsens the pre-synaptic phenotype at cortico-amygdala synaptic connections compared to Gdi1-null mice. These results suggest a pivotal role of αGDI via specific RAB GTPases acting specifically in forebrain regions at the pre-synaptic sites involved in memory formation.

Reduced brain perfusion in basal forebrain associated with cognitive decline in Alzheimer's diseases: a Tc-99m HMPAO SPECT study

International Nuclear Information System (INIS)

Lee, M.C.; Kang, H.; Kang, E.; Lee, J.S.; Lee, D.S.; Lee, D.W.; Cho, M.J.

2002-01-01

Aim: Reduction of regional cerebral blood flow (rCBF) in various cerebral regions and decline of cognitive function have been reported in Alzheimer's disease (AD) patients. The aim of this study was to identify the brain areas showing correlation between longitudinal changes of rCBFs and decline of general mental function, measured by Mini-Mental State Examination (MMSE) in probable Alzheimer's disease patients. Materials and Methods: Nine probable AD patients according to NINCDS-ADRDA criteria and DSM-IV were studied with Tc-99m HMPAO SPECT at an initial point and at the follow-up after a period of average 1.8 year. MMSE score was obtained in both occasions (average MMSE 16.4 at initial study; average MMSE = 8.1 at follow-up). Single SPECT was performed in 30 age-matched normal controls. Each SPECT image was normalized to the cerebellar activity. Using statistical parametric mapping (SPM99), correlation was analyzed between individual changes in rCBF of two SPECT scans and the MMSE scores at the time of each study in AD patients. In addition, the SPECT images of the initial study and the follow-up study were compared with SPECT images of the age-matched normal group respectively. Results: Significant correlation between longitudinal changes of rCBFs and MMSE scores was found in left basal forebrain region including substantia innominata (x, y, z = -24, 16, -23; P < .05, corrected). Within a short follow-up period of 1.8 years, cerebral hypoperfusion extended to various cortical regions from bilateral temporo-parietal to bilateral frontal regions and cingulate cortex, compared to normal controls. Conclusion: The decline of cognitive function in individual AD patients was correlated with rCBF reduction in left basal forebrain. This finding supports the cholinergic hypothesis of AD since hypoperfusion in basal forebrain region might indicate deterioration of cholinergic neurons in nucleus basalis of Meynert or substantia innominata
The cerebroprotective effect of dextromethorphan assessed by 1H and 31P NMR spectroscopy during global forebrain ischemia in the rat

International Nuclear Information System (INIS)

Tulleken, C.A.F.; Rijen, P.C. van; Berkelbach van der Sprenkel, J.W.; Verheul, H.B.; Echteld, C.J.A. van; Balasz, R.; Lewis, P.

1991-01-01

Global forebrain ischemia was induced in the rat model by occlusion of both carotid arteries and subsequent lowering of the blood pressure. After 30 minutes of ischemia reperfusion was established. Using 1H and 31P NMR spectroscopy tissue pH values, lactate production, cellular energy index and N-acetyl-aspartate content were determined. The survival rates and histological damage were counted. (author)
Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.

Science.gov (United States)

Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula

2017-08-02

Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social
Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

DEFF Research Database (Denmark)

Larsen, K.B.; Laursen, H.; Graem, N.

2008-01-01

Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...
Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using 125I-Bolton-Hunter-CCK8

International Nuclear Information System (INIS)

Niehoff, D.L.

1989-01-01

The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, 125 I-Bolton-Hunter-CCK8 ( 125 I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of 125 I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species
Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using sup 125 I-Bolton-Hunter-CCK8

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Niehoff, D.L. (Abbott Laboratories, Abbott Park, IL (USA))

1989-03-01

The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, {sup 125}I-Bolton-Hunter-CCK8 ({sup 125}I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of {sup 125}I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species.
Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

International Nuclear Information System (INIS)

Zhong, Yanjun; Dong, Guicheng; Luo, Haiguang; Cao, Jie; Wang, Chang; Wu, Jianyuan; Feng, Yu-Qi; Yue, Jiang

2012-01-01

Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.
Progressive supranuclear palsy: neuronal and glial cytoskeletal pathology in the higher order processing autonomic nuclei of the lower brainstem.

Science.gov (United States)

Rüb, U; Del Tredici, K; Schultz, C; de Vos, R A I; Jansen Steur, E N H; Arai, K; Braak, H

2002-02-01

The medial and lateral parabrachial nuclei (MPB, LPB), the gigantocellular reticular nucleus (GI), the raphes magnus (RMG) and raphes obscurus nuclei (ROB), as well as the intermediate reticular zone (IRZ) represent pivotal subordinate brainstem centres, all of which control autonomic functions. In this study, we investigated the occurrence and severity of the neuronal and glial cytoskeletal pathology in these six brainstem nuclei from 17 individuals with clinically diagnosed and neuropathologically confirmed progressive supranuclear palsy (PSP). The association between the severity of the pathology and the duration of the disease was investigated by means of correlation analysis. The brainstem nuclei in all of the PSP cases were affected by the neuronal cytoskeletal pathology, with the IRZ and GI regularly showing severe involvement, the MPB, RMG, and ROB marked involvement, and the LPB mild involvement. In the six nuclear greys studied, glial cells undergo alterations of their cytoskeleton on an irregular basis, whereby diseased oligodendrocytes predominantly presented as coiled bodies and affected astrocytes as thorn-shaped astrocytes. In all six nuclei, the severity of the neuronal or glial cytoskeletal pathology showed no correlation with the duration of PSP. In view of their functional role, the neuronal pathology in the nuclei studied offers a possible explanation for the autonomic dysfunctions that eventually develop in the course of PSP.
How microelectrode array-based chick forebrain neuron biosensors respond to glutamate NMDA receptor antagonist AP5 and GABAA receptor antagonist musimol

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Serena Y. Kuang

2016-09-01

Full Text Available We have established a long-term, stable primary chick forebrain neuron (FBN culture on a microelectrode array platform as a biosensor system for neurotoxicant screening and for neuroelectrophysiological studies for multiple purposes. This paper reports some of our results, which characterize the biosensor pharmacologically. Dose-response experiments were conducted using NMDA receptor antagonist AP5 and GABAA receptor agonist musimol (MUS. The chick FBN biosensor (C-FBN-biosensor responds to the two agents in a pattern similar to that of rodent counterparts; the estimated EC50s (the effective concentration that causes 50% inhibition of the maximal effect are 2.3 μM and 0.25 μM, respectively. Intercultural and intracultural reproducibility and long-term reusability of the C-FBN-biosensor are addressed and discussed. A phenomenon of sensitization of the biosensor that accompanies intracultural reproducibility in paired dose-response experiments for the same agent (AP5 or MUS is reported. The potential application of the C-FBN-biosensor as an alternative to rodent biosensors in shared sensing domains (NMDA receptor and GABAA receptor is suggested. Keywords: Biosensor, Microelectrode array, Neurotoxicity, Chick forebrain neuron, AP5, Musimol
The auditory brainstem response in two lizard species

DEFF Research Database (Denmark)

Brittan-Powell, Elizabeth F; Christensen-Dalsgaard, Jakob; Tang, Yezhong

2010-01-01

Although lizards have highly sensitive ears, it is difficult to condition them to sound, making standard psychophysical assays of hearing sensitivity impractical. This paper describes non-invasive measurements of the auditory brainstem response (ABR) in both Tokay geckos (Gekko gecko; nocturnal...... animals, known for their loud vocalizations) and the green anole (Anolis carolinensis, diurnal, non-vocal animals). Hearing sensitivity was measured in 5 geckos and 7 anoles. The lizards were sedated with isoflurane, and ABRs were measured at levels of 1 and 3% isoflurane. The typical ABR waveform......). Above 5 kHz, however, anoles were more than 20 dB more sensitive than geckos and showed a wider range of sensitivity (1-7 kHz). Generally, thresholds from ABR audiograms were comparable to those of small birds. Best hearing sensitivity, however, extended over a larger frequency range in lizards than...
Axonal sprouting of a brainstem-spinal pathway after estrogen administration in the adult female rhesus monkey

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Vanderhorst, VGJM; Terasawa, E; Ralston, HJ

2002-01-01

The nucleus retroambiguus (NRA) is located in the caudal medulla oblongata and contains premotor neurons that project to motoneuronal cell groups in the brainstem and spinal cord. NRA projections to the lumbosacral cord are species specific and might be involved in mating behavior. In the female
Limbic encephalitis with antibodies to glutamic acid decarboxylase presenting with brainstem symptoms

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Faruk Incecik

2015-01-01

Full Text Available Limbic encephalitis (LE is a neurological syndrome that may present in association with cancer, infection, or as an isolate clinical condition often accompanying autoimmune disorders. LE associated with glutamic acid decarboxylase antibodies (anti-GAD is rare in children. Here, we characterized the clinical and laboratory features of a patient presenting with brainstem involvement with non-paraneoplastic LE associated with anti-GAD antibodies. In our patient, after plasma exchange, we determined a dramatic improvement of the neurological deficits.
Diffuse and focal presentations of brainstem tumors in children: the images and the prognostic value

International Nuclear Information System (INIS)

Menor, F.; Canete, A.; Romero, M. J.; Trilles, L.; Carvajal, E.; Marti-Bonmati, L.

2000-01-01

To determine whether the presentation of brainstem tumors as diffuse or focal lesions showed any prognostic value in children. A retrospective review was carried out of the neuroradiological findings in 43 children with brainstem tumors, all of whom underwent computed tomography (CT) and 31 of whom underwent magnetic resonance (MR). The diffuse tumors (n=20) were all located in the pons, spreading to mesencephalon in 6 cases and to medulla oblongata in 1, and exhibiting exophytic growth, preferentially to the prepontine cistern. They presented homogeneous low attenuation in CT (90%) and decrease/increased signal intensity in T1/T2-weighted MR images (91.6%). Contrast uptake was observed in 20% of cases, with agreement between CT and MR. The patients showed a good initial response to treatment (70%), a high rate of relapse (80%) and a 5-year survival of 12%. The focal tumors were located in the pons (11 cases, spreading to the medulla oblongata in 2), mesencephalon (11 cases, 9 tectal and 2 peduncular) and medulla oblongata (1 case), and exhibited exophytic growth predominantly to the pontocerebellar junction and to the cerebellar peduncles. They showed a certain tendency toward heterogeneity (21.7%), toward isoattenuation in CT (47.8%) and isointensity in T1-weighted MR images (26.3%). CT showed a rate of tumor uptake of 26%, while the rate of contrast iptake was 58% MR. Fifty percent of these lesions responded well to therapy, with a recurrence rate of 28% and 4-year survival of 63%. Neuroimaging helps to define two basic patterns in brainstem tumors that play a role in prognosis. The diffuse tumor, which characteristically shows a good initial response to therapy, has a worse prognosis, probably reflecting its histological aggressiveness. (Author) 21 refs
Effect of edaravone on acute brainstem-cerebellar infarction with vertigo and sudden hearing loss.

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Inoue, Yuta; Yabe, Takao; Okada, Kazunari; Nakamura, Yuka

2014-06-01

We report 2 cases with acute brainstem and brainstem-cerebellar infarction showed improvement of their signs and symptoms after administration of edaravone. Case 1, a 74-year-old woman who experienced sudden vertigo, also had dysarthria and left hemiplegia. Magnetic resonance imaging (MRI) showed an abnormal region in the right ventrolateral medulla oblongata. The patient's vertigo and hemiplegia improved completely after treatment. Case 2, a 50-year-old man who experienced sudden vertigo and sensorineural hearing loss (SNHL), developed dysarthria after admission. MRI revealed acute infarction in the right cerebellar hemisphere. Magnetic resonance angiography revealed dissection of the basilar artery and occlusion of the right anterior inferior cerebellar artery. The patient's vertigo and hearing remarkably improved. We have described 2 patients whose early symptoms were vertigo and sudden SNHL, but who were later shown to have ischemic lesions of the central nervous system. Edaravone is neuroprotective drug with free radical-scavenging actions. Free radicals in the ear are responsible for ischemic damage. Edaravone, a free radical scavenger, may be useful in the treatment of vertigo and SNHL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Comparison of Auditory Brainstem Response in Noise Induced Tinnitus and Non-Tinnitus Control Subjects

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Ghassem Mohammadkhani

2009-12-01

Full Text Available Background and Aim: Tinnitus is an unpleasant sound which can cause some behavioral disorders. According to evidence the origin of tinnitus is not only in peripheral but also in central auditory system. So evaluation of central auditory system function is necessary. In this study Auditory brainstem responses (ABR were compared in noise induced tinnitus and non-tinnitus control subjects.Materials and Methods: This cross-sectional, descriptive and analytic study is conducted in 60 cases in two groups including of 30 noise induced tinnitus and 30 non-tinnitus control subjects. ABRs were recorded ipsilateraly and contralateraly and their latencies and amplitudes were analyzed.Results: Mean interpeak latencies of III-V (p= 0.022, I-V (p=0.033 in ipsilatral electrode array and mean absolute latencies of IV (p=0.015 and V (p=0.048 in contralatral electrode array were significantly increased in noise induced tinnitus group relative to control group. Conclusion: It can be concluded from that there are some decrease in neural transmission time in brainstem and there are some sign of involvement of medial nuclei in olivery complex in addition to lateral lemniscus.
Musicians and Tone-Language Speakers Share Enhanced Brainstem Encoding but Not Perceptual Benefits for Musical Pitch

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Bidelman, Gavin M.; Gandour, Jackson T.; Krishnan, Ananthanarayan

2011-01-01

Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians…
Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.

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Miller, V M; Zhu, Y; Bucher, C; McGinnis, W; Ryan, L K; Siegel, A; Zalcman, S

2013-10-01

The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure
Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats.

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Ventskovska, Olena; Porkka-Heiskanen, Tarja; Karpova, Nina N

2015-04-01

Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf by sleep or sleep deprivation. Here we investigated whether 5-methylcytosine (5mC) DNA modification at Bdnf promoters p1, p4 and p9 influences Bdnf1, Bdnf4 and Bdnf9a expression during the normal inactive phase or after sleep deprivation (SD) (3, 6 and 12 h, end-times being ZT3, ZT6 and ZT12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical Bdnf expression: Bdnf1 expression was highest at ZT6 and Bdnf4 lowest at ZT12. Such variation was not observed in the basal forebrain. Also Bdnf p1 and p9 methylation levels differed only in the cortex, while Bdnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced Bdnf1 and Bdnf4 with the similar pattern for Bdnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5mC levels at the cortical Bdnf p4 and p9. Regression analysis between the 5mC promoter levels and the corresponding Bdnf transcript expression revealed significant negative correlations for the basal forebrain Bdnf1 and cortical Bdnf9a transcripts in only non-deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that Bdnf transcription during the light phase of undisturbed sleep-wake cycle but not after SD is regulated at least partially by brain site-specific DNA methylation. © 2014 European Sleep Research Society.
FMRP acts as a key messenger for dopamine modulation in the forebrain.

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Wang, Hansen; Wu, Long-Jun; Kim, Susan S; Lee, Frank J S; Gong, Bo; Toyoda, Hiroki; Ren, Ming; Shang, Yu-Ze; Xu, Hui; Liu, Fang; Zhao, Ming-Gao; Zhuo, Min

2008-08-28

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that controls translational efficiency and regulates synaptic plasticity. Here, we report that FMRP is involved in dopamine (DA) modulation of synaptic potentiation. AMPA glutamate receptor subtype 1 (GluR1) surface expression and phosphorylation in response to D1 receptor stimulation were reduced in cultured Fmr1(-/-) prefrontal cortex (PFC) neurons. Furthermore, D1 receptor signaling was impaired, accompanied by D1 receptor hyperphosphorylation at serine sites and subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in both PFC and striatum of Fmr1(-/-) mice. FMRP interacted with GRK2, and pharmacological inhibition of GRK2 rescued D1 receptor signaling in Fmr1(-/-) neurons. Finally, D1 receptor agonist partially rescued hyperactivity and enhanced the motor function of Fmr1(-/-) mice. Our study has identified FMRP as a key messenger for DA modulation in the forebrain and may provide insights into the cellular and molecular mechanisms underlying fragile X syndrome.
Beyond dreams: do sleep-related movements contribute to brain development?

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Mark S Blumberg

2010-11-01

Full Text Available Conventional wisdom has long held that the twitches of sleeping infants and adults are by-products of a dreaming brain. With the discovery of active (or REM sleep in the 1950s and the recognition soon thereafter that active sleep is characterized by inhibition of motor outflow, researchers elaborated on conventional wisdom and concluded that sleep-related twitches are epiphenomena that result from incomplete blockade of dream-related cortical activity. This view persists despite the fact that twitching is unaffected in infant and adults when the cortex is disconnected from the brainstem. In 1966, Roffwarg and colleagues introduced the ontogenetic hypothesis, which addressed the preponderance of active sleep in early infancy. This hypothesis posited that the brainstem mechanisms that produce active sleep provide direct ascending stimulation to the forebrain and descending stimulation to the musculature, thereby promoting brain and neuromuscular development. However, this hypothesis and the subsequent work that tested it did not directly address the developmental significance of twitching or sensory feedback as a contributor to activity-dependent development. Here I review recent findings that have inspired an elaboration of the ontogenetic hypothesis. Specifically, in addition to direct brainstem activation of cortex during active sleep, sensory feedback arising from limb twitches produces discrete and substantial activation of somatosensory cortex and, beyond that, of hippocampus. Delineating how twitching during active sleep contributes to the establishment, refinement, and maintenance of neural circuits may aid our understanding of the early developmental events that make sensorimotor integration possible. In addition, twitches may prove to be sensitive and powerful tools for assessing somatosensory function in humans across the lifespan as well as functional recovery in individuals with injuries or conditions that affect sensorimotor function.

Activation of Brainstem Pro-opiomelanocortin Neurons Produces Opioidergic Analgesia, Bradycardia and Bradypnoea.

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Cerritelli, Serena; Hirschberg, Stefan; Hill, Rob; Balthasar, Nina; Pickering, Anthony E

2016-01-01

Opioids are widely used medicinally as analgesics and abused for hedonic effects, actions that are each complicated by substantial risks such as cardiorespiratory depression. These drugs mimic peptides such as β-endorphin, which has a key role in endogenous analgesia. The β-endorphin in the central nervous system originates from pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and nucleus of the solitary tract (NTS). Relatively little is known about the NTSPOMC neurons but their position within the sensory nucleus of the vagus led us to test the hypothesis that they play a role in modulation of cardiorespiratory and nociceptive control. The NTSPOMC neurons were targeted using viral vectors in a POMC-Cre mouse line to express either opto-genetic (channelrhodopsin-2) or chemo-genetic (Pharmacologically Selective Actuator Modules). Opto-genetic activation of the NTSPOMC neurons in the working heart brainstem preparation (n = 21) evoked a reliable, titratable and time-locked respiratory inhibition (120% increase in inter-breath interval) with a bradycardia (125±26 beats per minute) and augmented respiratory sinus arrhythmia (58% increase). Chemo-genetic activation of NTSPOMC neurons in vivo was anti-nociceptive in the tail flick assay (latency increased by 126±65%, pneurons were found to project to key brainstem structures involved in cardiorespiratory control (nucleus ambiguus and ventral respiratory group) and endogenous analgesia (periaqueductal gray and midline raphe). Thus the NTSPOMC neurons may be capable of tuning behaviour by an opioidergic modulation of nociceptive, respiratory and cardiac control.
Ontogeny of cholecystokinin-like immunoreactivity in the Brazilian opossum brain.

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Fox, C A; Jeyapalan, M; Ross, L R; Jacobson, C D

1991-12-17

We have studied the anatomical distribution of cholecystokinin-like immunoreactive (CCK-IR) somata and fibers in the brain of the adult and developing Brazilian short-tailed opossum, Monodelphis domestica. Animals ranged in age from the day of birth (1PN) to young adulthood (180PN). A nickel enhanced, avidin-biotin, indirect immunohistochemical technique was used to identify CCK-IR structures. Somata containing CCK immunoreactivity were observed in the cerebral cortex, hippocampus, hypothalamus, thalamus, midbrain, and brainstem in the adult. Cholecystokinin immunoreactive fibers had a wide distribution in the adult Monodelphis brain. The only major region of the brain that did not contain CCK-IR fibers was the cerebellum. The earliest expression of CCK immunoreactivity was found in fibers in the dorsal brainstem of 5-day-old opossum pups. It is possible that the CCK-IR fibers in the brainstem at 5PN are of vagal origin. Cholecystokinin immunoreactive somata were observed in the brainstem on 10PN. The CCK-IR cell bodies observed in the brainstem at 10PN may mark the first expression of CCK-IR elements intrinsic to the brain. A broad spectrum of patterns of onset of CCK expression was observed in the opossum brain. The early occurrence and varied ontogenesis of CCK-IR structures indicates CCK may be involved in the function of a variety of circuits from the brainstem to the cerebral cortex. The early expression of CCK-IR structures in the dorsal brainstem suggests that CCK may modulate feeding behavior in the Monodelphis neonate. Cholecystokinin immunoreactivity in forebrain structures such as the suprachiasmatic nucleus, medial preoptic area, thalamus and cortical structures indicates that CCK may also be involved in circadian rhythmicity, reproductive functions, as well as the state of arousal of the Brazilian opossum. The ontogenic timing of CCK immunoreactivity in specific circuitry also indicates that CCK expression does not occur simultaneously throughout the
Collateralization of descending spinal pathways from red nucleus and other brainstem cell groups in rat, cat and monkey

NARCIS (Netherlands)

A.M. Huisman (Margriet)

1983-01-01

textabstractThe somatotopically organized rubrospinal pathway is the major component of the laterally descending brainstem pathways, and is especially involved in steering of fractionated movements of the distal parts of the limbs. Electrophysiological studies in cat showed that this fiber
Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

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Sessle, B J

2000-01-01

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.
Mutations in ZIC2 in human holoprosencephaly: description of a Novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals

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Solomon, Benjamin D.; Lacbawan, Felicitas; Mercier, Sandra; Clegg, Nancy J.; Delgado, Mauricio R.; Rosenbaum, Kenneth; Dubourg, Christèle; David, Veronique; Olney, Ann Haskins; Wehner, Lars-Erik; Hehr, Ute; Bale, Sherri; Paulussen, Aimee; Smeets, Hubert J.; Hardisty, Emily; Tylki-Szymanska, Anna; Pronicka, Ewa; Clemens, Michelle; McPherson, Elizabeth; Hennekam, Raoul C. M.; Hahn, Jin; Stashinko, Elaine; Levey, Eric; Wieczorek, Dagmar; Roeder, Elizabeth; Schell-Apacik, Chayim Can; Booth, Carol W.; Thomas, Ronald L.; Kenwrick, Sue; Cummings, Derek A. T.; Bous, Sophia M.; Keaton, Amelia; Balog, Joan Z.; Hadley, Donald; Zhou, Nan; Long, Robert; Vélez, Jorge I.; Pineda-Alvarez, Daniel E.; Odent, Sylvie; Roessler, Erich; Muenke, Maximilian

2010-01-01

BACKGROUND: Holoprosencephaly (HPE), the most common malformation of the human forebrain, may be due to mutations in genes associated with non-syndromic HPE. Mutations in ZIC2, located on chromosome 13q32, are a common cause of non-syndromic, non-chromosomal HPE. OBJECTIVE: To characterise genetic
Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring.

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Ferreira, Diorginis Soares; Liu, Yuri; Fernandes, Mariana Pinheiro; Lagranha, Claudia Jacques

2016-10-01

Studies in humans and animal models have established a close relationship between early environment insult and subsequent risk of development of non-communicable diseases, including the cardiovascular. Whereas experimental evidences highlight the early undernutrition and the late cardiovascular disease relation, the central mechanisms linking the two remain unknown. Owing to the oxidative balance influence in several pathologies, the aim of the present study was to evaluate the effects of maternal undernutrition (i.e. a low-protein (LP) diet) on oxidative balance in the brainstem. Male rats from mothers fed with an LP diet (8% casein) throughout the perinatal period (i.e. gestation and lactation) showed 10× higher lipid peroxidation levels than animals treated with normoprotein (17% casein) at 100 days of age. In addition, we observed the following reductions in enzymatic activities: superoxide dismutase, 16%; catalase, 30%; glutathione peroxidase, 34%; glutathione-S-transferase, 51%; glutathione reductase, 23%; glucose-6-phosphate dehydrogenase, 31%; and in non-enzymatic glutathione system, 46%. This study is the first to focus on the role of maternal LP nutrition in oxidative balance in a central nervous system structure responsible for cardiovascular control in adult rats. Our data observed changes in oxidative balance in the offspring, therefore, bring a new concept related to early undernutrition and can help in the development of a new clinical strategy to combat the effects of nutritional insult. Wherein the central oxidative imbalance is a feasible mechanism underlying the hypertension risk in adulthood triggered by maternal LP diet.
Cytoskeletal Regulation Dominates Temperature-Sensitive Proteomic Changes of Hibernation in Forebrain of 13-Lined Ground Squirrels

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Hindle, Allyson G.; Martin, Sandra L.

2013-01-01

13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy – wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase
Cytoskeletal regulation dominates temperature-sensitive proteomic changes of hibernation in forebrain of 13-lined ground squirrels.

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Allyson G Hindle

Full Text Available 13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy - wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins
Large central lesions compressing the hypothalamus and brainstem. Operative approaches and combination treatment with radiosurgery

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Inoue, Hiroshi K.; Negishi, Masatoshi; Kohga, Hideaki; Hirato, Masafumi; Ohye, Chihiro [Gunma Univ., Maebashi (Japan). School of Medicine; Shibazaki, Tohru

1998-09-01

A major aim of minimally invasive neurosurgery is to preserve function in the brain and cranial nerves. Based on previous results of radiosurgery for central lesions (19 craniopharyngiomas, 46 pituitary adenomas, 9 meningeal tumors), combined micro- and/or radiosurgery was applied for large lesions compressing the hypothalamus and/or brainstem. A basal interhemispheric approach via superomedial orbitotomy or a transcallosal-transforaminal approach was used for these large tumors. Tumors left behind in the hypothalamus or cavernous sinus were treated with radiosurgery using a gamma unit. Preoperative hypothalamo-pituitary functions were preserved in most of these patients. Radiosurgical results were evaluated in patients followed for more than 2 years after treatment. All 9 craniopharyngiomas decreased in size after radiosurgery, although a second treatment was required in 4 patients. All 20 pituitary adenomas were stable or decreased in size and 5 of 7 functioning adenomas showed normalized values of hormones in the serum. All 3 meningeal tumors were stable or decreased in size after treatment. No cavernous sinus symptoms developed after radiosurgery. We conclude that combined micro- and radio-neurosurgery is an effective and less invasive treatment for large central lesions compressing the hypothalamus and brainstem. (author)
Large central lesions compressing the hypothalamus and brainstem. Operative approaches and combination treatment with radiosurgery

International Nuclear Information System (INIS)

Inoue, Hiroshi K.; Negishi, Masatoshi; Kohga, Hideaki; Hirato, Masafumi; Ohye, Chihiro; Shibazaki, Tohru

1998-01-01

A major aim of minimally invasive neurosurgery is to preserve function in the brain and cranial nerves. Based on previous results of radiosurgery for central lesions (19 craniopharyngiomas, 46 pituitary adenomas, 9 meningeal tumors), combined micro- and/or radiosurgery was applied for large lesions compressing the hypothalamus and/or brainstem. A basal interhemispheric approach via superomedial orbitotomy or a transcallosal-transforaminal approach was used for these large tumors. Tumors left behind in the hypothalamus or cavernous sinus were treated with radiosurgery using a gamma unit. Preoperative hypothalamo-pituitary functions were preserved in most of these patients. Radiosurgical results were evaluated in patients followed for more than 2 years after treatment. All 9 craniopharyngiomas decreased in size after radiosurgery, although a second treatment was required in 4 patients. All 20 pituitary adenomas were stable or decreased in size and 5 of 7 functioning adenomas showed normalized values of hormones in the serum. All 3 meningeal tumors were stable or decreased in size after treatment. No cavernous sinus symptoms developed after radiosurgery. We conclude that combined micro- and radio-neurosurgery is an effective and less invasive treatment for large central lesions compressing the hypothalamus and brainstem. (author)
Interactions between Brainstem Noradrenergic Neurons and the Nucleus Accumbens Shell in Modulating Memory for Emotionally Arousing Events

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Kerfoot, Erin C.; Williams, Cedric L.

2011-01-01

The nucleus accumbens shell (NAC) receives axons containing dopamine-[beta]-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these…
Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study.

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Zant, Janneke C; Kim, Tae; Prokai, Laszlo; Szarka, Szabolcs; McNally, James; McKenna, James T; Shukla, Charu; Yang, Chun; Kalinchuk, Anna V; McCarley, Robert W; Brown, Ritchie E; Basheer, Radhika

2016-02-10

Understanding the control of sleep-wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep-wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that "selective" stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of "selective" optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non-cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. Optogenetics is a revolutionary tool to assess the roles of particular groups of neurons in behavioral
Coping with flow: behavior, neurophysiology and modeling of the fish lateral line system.

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Mogdans, Joachim; Bleckmann, Horst

2012-12-01

With the mechanosensory lateral line fish perceive water motions relative to their body surface and local pressure gradients. The lateral line plays an important role in many fish behaviors including the detection and localization of dipole sources and the tracking of prey fish. The sensory units of the lateral line are the neuromasts which are distributed across the surface of the animal. Water motions are received and transduced into neuronal signals by the neuromasts. These signals are conveyed by afferent nerve fibers to the fish brain and processed by lateral line neurons in parts of the brainstem, cerebellum, midbrain, and forebrain. In the cerebellum, midbrain, and forebrain, lateral line information is integrated with sensory information from other modalities. The present review introduces the peripheral morphology of the lateral line, and describes our understanding of lateral line physiology and behavior. It focuses on recent studies that have investigated: how fish behave in unsteady flow; what kind of sensory information is provided by flow; and how fish use and process this information. Finally, it reports new theoretical and biomimetic approaches to understand lateral line function.
Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study.

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Robert Edward Sims

Full Text Available Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K(+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.
Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

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Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

2010-08-01

Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.
The Monoamine Brainstem Reticular Formation as a Paradigm for Re-Defining Various Phenotypes of Parkinson's Disease Owing Genetic and Anatomical Specificity.

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Gambardella, Stefano; Ferese, Rosangela; Biagioni, Francesca; Busceti, Carla L; Campopiano, Rosa; Griguoli, Anna M P; Limanaqi, Fiona; Novelli, Giuseppe; Storto, Marianna; Fornai, Francesco

2017-01-01

The functional anatomy of the reticular formation (RF) encompasses a constellation of brain regions which are reciprocally connected to sub-serve a variety of functions. Recent evidence indicates that neuronal degeneration within one of these regions spreads synaptically along brainstem circuitries. This is exemplified by the recruitment of various brainstem reticular nuclei in specific Parkinson's disease (PD) phenotypes, and by retrospective analysis of lethargic post-encephalitic parkinsonism. In fact, the spreading to various monoamine reticular nuclei can be associated with occurrence of specific motor and non-motor symptoms (NMS). This led to re-consider PD as a brainstem monoamine disorder (BMD). This definition surpasses the anatomy of meso-striatal motor control to include a variety of non-motor domains. This concept clearly emerges from the quite specific clinical-anatomical correlation which can be drawn in specific paradigms of PD genotypes. Therefore, this review article focuses on the genetics and neuroanatomy of three PD genotypes/phenotypes which can be selected as prototype paradigms for a differential recruitment of the RF leading to differential occurrence of NMS: (i) Parkin-PD, where NMS are rarely reported; (ii) LRRK2-PD and slight SNC point mutations, where the prevalence of NMS resembles idiopathic PD; (iii) Severe SNCA point mutations and multiplications, where NMS are highly represented.
Combined laryngeal inflammation and trauma mediate long-lasting immunoreactivity response in the brainstem sensory nuclei in the rat

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Kristina eSimonyan

2012-11-01

Full Text Available Somatosensory feedback from the larynx plays a critical role in regulation of normal upper airway functions, such as breathing, deglutition and voice production, while altered laryngeal sensory feedback is known to elicit a variety of pathological reflex responses, including persistent coughing, dysphonia and laryngospasm. Despite its clinical impact, the central mechanisms underlying the development of pathological laryngeal responses remain poorly understood. We examined the effects of persistent vocal fold (VF inflammation and trauma, as frequent causes of long-lasting modulation of laryngeal sensory feedback, on brainstem immunoreactivity in the rat. Combined VF inflammation and trauma were induced by injection of lipopolysaccharide (LPS solution and compared to VF trauma alone from injection of vehicle solution and to controls without any VF manipulations. Using a c-fos marker, we found significantly increased Fos-like immunoreactivity (FLI in the bilateral intermediate/parvicellular reticular formation (IRF/PCRF with a trend in the left solitary tract nucleus (NTS only in animals with LPS-induced VF inflammation and trauma. Further, FLI in the right NTS was significantly correlated with the severity of LPS-induced VF changes. However, increased brainstem FLI response was not associated with FLI changes in the first-order neurons of the laryngeal afferents located in the nodose and jugular ganglia in either group. Our data indicate that complex VF alterations (i.e., inflammation/trauma vs. trauma alone may cause prolonged excitability of the brainstem nuclei receiving a direct sensory input from the larynx, which, in turn, may lead to (malplastic changes within the laryngeal central sensory control.
Auditory Brainstem Response Wave Amplitude Characteristics as a Diagnostic Tool in Children with Speech Delay with Unknown Causes

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Susan Abadi

2016-09-01

Full Text Available Speech delay with an unknown cause is a problem among children. This diagnosis is the last differential diagnosis after observing normal findings in routine hearing tests. The present study was undertaken to determine whether auditory brainstem responses to click stimuli are different between normally developing children and children suffering from delayed speech with unknown causes. In this cross-sectional study, we compared click auditory brainstem responses between 261 children who were clinically diagnosed with delayed speech with unknown causes based on normal routine auditory test findings and neurological examinations and had >12 months of speech delay (case group and 261 age- and sex-matched normally developing children (control group. Our results indicated that the case group exhibited significantly higher wave amplitude responses to click stimuli (waves I, III, and V than did the control group (P=0.001. These amplitudes were significantly reduced after 1 year (P=0.001; however, they were still significantly higher than those of the control group (P=0.001. The significant differences were seen regardless of the age and the sex of the participants. There were no statistically significant differences between the 2 groups considering the latency of waves I, III, and V. In conclusion, the higher amplitudes of waves I, III, and V, which were observed in the auditory brainstem responses to click stimuli among the patients with speech delay with unknown causes, might be used as a diagnostic tool to track patients’ improvement after treatment.
Dopamine receptor gene expression by enkephalin neurons in rat forebrain

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Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B.

1990-01-01

In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons
Dopamine receptor gene expression by enkephalin neurons in rat forebrain

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Le Moine, C.; Normand, E.; Guitteny, A.F.; Fouque, B.; Teoule, R.; Bloch, B. (Universite de Bordeaux II (France))

1990-01-01

In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of the substantia nigra, ventral tegmental area, and forebrain, especially in caudate putamen, nucleus accumbens, olfactory tubercle, and piriform cortex. Hybridization with D2 and preproenkephalin A probes in adjacent sections, as well as combined hybridization with the two probes in the same sections, demonstrated that all detectable enkephalin neurons in the striatum contained the D2 receptor mRNA. Large neurons in caudate putamen, which were unlabeled with the preproenkephalin A probe and which may have been cholinergic, also expressed the D2 receptor gene. Haloperidol treatment (14 or 21 days) provoked an increase in mRNA content for D2 receptor and preproenkephalin A in the striatum. This suggests that the increase in D2 receptor number observed after haloperidol treatment is due to increased activity of the D2 gene. These results indicate that in the striatum, the enkephalin neurons are direct targets for dopamine liberated from mesostriatal neurons.

Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development

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Congyu Xu

2017-10-01

Full Text Available Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.
Astrocitary niches in human adult medulla oblongata.

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Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

2013-04-01

Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density. Copyright © 2012 Elsevier GmbH. All rights reserved.
Exploding Head Syndrome as Aura of Migraine with Brainstem Aura: A Case Report.

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Rossi, Fabian H; Gonzalez, Elizabeth; Rossi, Elisa Marie; Tsakadze, Nina

2018-01-01

This article reports a case of exploding head syndrome (EHS) as an aura of migraine with brainstem aura (MBA). A middle-aged man presented with intermittent episodes of a brief sensation of explosion in the head, visual flashing, vertigo, hearing loss, tinnitus, confusion, ataxia, dysarthria, and bilateral visual impairment followed by migraine headache. The condition was diagnosed as MBA. Explosive head sensation, sensory phenomena, and headaches improved over time with nortriptyline. This case shows that EHS can present as a primary aura symptom in patients with MBA.
The mRNA expression and histological integrity in rat forebrain motor and sensory regions are minimally affected by acrylamide exposure through drinking water

International Nuclear Information System (INIS)

Bowyer, John F.; Latendresse, John R.; Delongchamp, Robert R.; Warbritton, Alan R.; Thomas, Monzy; Divine, Becky; Doerge, Daniel R.

2009-01-01

A study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum, substantia nigra and parietal cortex of rat after a 2-week acrylamide exposure. The highest dose tested (maximally tolerated) of approximately 44 mg/kg/day resulted in a significant decreased body weight, sluggishness, and locomotor activity reduction. These physiological effects were not accompanied by prominent changes in gene expression in the forebrain. All the expression changes seen in the 1200 genes that were evaluated in the three brain regions were ≤ 1.5-fold, and most not significant. Very few, if any, statistically significant changes were seen in mRNA levels of the more than 50 genes directly related to the cholinergic, noradrenergic, GABAergic or glutamatergic neurotransmitter systems in the striatum, substantia nigra or parietal cortex. All the expression changes observed in genes related to dopaminergic function were less than 1.5-fold and not statistically significant and the 5HT1b receptor was the only serotonin-related gene affected. Therefore, gene expression changes were few and modest in basal ganglia and sensory cortex at a time when the behavioral manifestations of acrylamide toxicity had become prominent. No histological evidence of axonal, dendritic or neuronal cell body damage was found in the forebrain due to the acrylamide exposure. As well, microglial activation was not present. These findings are consistent with the absence of expression changes in genes related to changes in neuroinflammation or neurotoxicity. Over all, these data suggest that oral ingestion of acrylamide in drinking water or food, even at maximally tolerable levels, induced neither marked changes in gene expression nor neurotoxicity in the motor and
Anatomical details of the brainstem and cranial nerves visualized by high resolution readout-segmented multi-shot echo-planar diffusion-weighted images using unidirectional MPG at 3T

International Nuclear Information System (INIS)

Naganawa, Shinji; Yamazaki, Masahiro; Kawai, Hisashi; Sone, Michihiko; Nakashima, Tsutomu; Isoda, Haruo

2011-01-01

We compared diffusion-weighted imaging (DWI) with readout-segmented multi-shot echo-planar imaging (rs-EPI) and single-shot EPI, both using unidirectional motion-probing gradient, in 10 patients for visualization of the anatomical structures in the brainstem. DWI by rs-EPI was significantly better than DWI by single-shot EPI for visualizing the medial longitudinal fasciculus, lateral lemniscus, corticospinal tract, and seventh/eighth cranial nerves and offered significantly less distortion of the brainstem. (author)
Functional Neuroanatomy of Human Cortex Cerebri in Relation to Wanting Sex and Having It

NARCIS (Netherlands)

Georgiadis, Janniko R.

Neuroanatomical textbooks typically restrict the central nervous system control of sexual responsiveness to the hypothalamus, brainstem and spinal cord. However, for all its primitive functions human sex is surprisingly complex and versatile. This review aims to extend the neuroanatomy of sexual
Direct Induction and Functional Maturation of Forebrain GABAergic Neurons from Human Pluripotent Stem Cells

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Alfred Xuyang Sun

2016-08-01

Full Text Available Gamma-aminobutyric acid (GABA-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs into GABAergic neurons (iGNs with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6–8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs. Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons.
Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

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Leeman Jonathan E

2012-07-01

Full Text Available Abstract Background Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS of brainstem metastases. Methods We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89. Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44% had received whole brain radiation therapy (WBRT prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%. The median tumor volume was 0.94 cm3 (range: 0.01-4.2 with a median prescription dose of 17 Gy (range: 12–24 delivered in 1–5 fractions. Results Median follow-up for the cohort was 3.2 months (range: 0.4-20.6. Nineteen patients (52% had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79% experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40% had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of
A comparative study of blood flow in the cerebellum and brainstem between Machado-Joseph disease and olivopontocerebellar atrophy

International Nuclear Information System (INIS)

Fukumitsu, Nobuyoshi; Suzuki, Masahiko; Ito Yasuhiko; Iguchi, Yasuyuki; Mori, Yutaka

2002-01-01

In recent years, the neurogenic and pathological differences between Machado-Joseph disease (MJD) and sporadic olivopontocerebellar atrophy (OPCA) have been clarified. We performed N-isopropyl-p-[I-123] iodoamphetamine (IMP) SPECT on 9 patients with MJD and 12 patients with OPCA. The blood flow of the cerebellum in the MJD group was significantly decreased than that of the control group (p<0.0001). That of OPCA group was significantly decreased than those of the control and MJD groups (p<0.0001, respectively). The blood flow of the brainstem in the MJD group was significantly decreased than that of the control group (p<0.001). That of OPCA group was significantly decreased than those of the control and MJD groups (p<0.0001, respectively). The blood flow of cerebellum and brainstem in the OPCA group were much decreased than those of MJD group. IMP distribution pattern in MJD patients obviously differed from that of OPCA patients. (author)
Brainstem GLP-1 signalling contributes to cancer anorexia-cachexia syndrome in the rat.

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Borner, Tito; Liberini, Claudia G; Lutz, Thomas A; Riediger, Thomas

2018-03-15

The cancer anorexia-cachexia syndrome (CACS) is a frequent and severe condition in cancer patients. Currently, no pharmacological treatment is approved for the therapy of CACS. Centrally, glucagon-like peptide-1 (GLP-1) is expressed in the nucleus tractus solitarii (NTS) and is implicated in malaise, nausea and food aversion. The NTS is reciprocally connected to brain sites implicated in the control of energy balance including the area postrema (AP), which mediates CACS in certain tumour models. Given the role of GLP-1 as a mediator of anorexia under acute sickness conditions, we hypothesized that brainstem GLP-1 signalling might play a role in the mediation of CACS. Using hepatoma tumour-bearing (TB) rats, we first tested whether the chronic delivery of the GLP-1R antagonist exendin-9 (Ex-9) into the fourth ventricle attenuates CACS. Second, we investigated whether a genetic knockdown of GLP-1 expression in the NTS ameliorates CACS. Ex-9 attenuated anorexia, body weight loss, muscle and fat depletion compared to TB controls. Similarly, TB animals with a knockdown of GLP-1 expression in the NTS had higher food intake, reduced body weight loss, and higher lean and fat mass compared to TB controls. Our study identifies brainstem GLP-1 as crucial mediator of CACS in hepatoma TB rats. The GLP-1R represents a promising target against CACS and possibly other forms of disease-related anorexia/cachexia. Copyright © 2017 Elsevier Ltd. All rights reserved.
PAM50: Unbiased multimodal template of the brainstem and spinal cord aligned with the ICBM152 space.

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De Leener, Benjamin; Fonov, Vladimir S; Collins, D Louis; Callot, Virginie; Stikov, Nikola; Cohen-Adad, Julien

2018-01-15

Template-based analysis of multi-parametric MRI data of the spinal cord sets the foundation for standardization and reproducibility, thereby helping the discovery of new biomarkers of spinal-related diseases. While MRI templates of the spinal cord have been recently introduced, none of them cover the entire spinal cord. In this study, we introduced an unbiased multimodal MRI template of the spinal cord and the brainstem, called PAM50, which is anatomically compatible with the ICBM152 brain template and uses the same coordinate system. The PAM50 template is based on 50 healthy subjects, covers the full spinal cord (C1 to L2 vertebral levels) and the brainstem, is available for T1-, T2-and T2*-weighted MRI contrasts and includes a probabilistic atlas of the gray matter and white matter tracts. Template creation accuracy was assessed by computing the mean and maximum distance error between each individual spinal cord centerline and the PAM50 centerline, after registration to the template. Results showed high accuracy for both T1- (mean = 0.37 ± 0.06 mm; max = 1.39 ± 0.58 mm) and T2-weighted (mean = 0.11 ± 0.03 mm; max = 0.71 ± 0.27 mm) contrasts. Additionally, the preservation of the spinal cord topology during the template creation process was verified by comparing the cross-sectional area (CSA) profile, averaged over all subjects, and the CSA profile of the PAM50 template. The fusion of the PAM50 and ICBM152 templates will facilitate group and multi-center studies of combined brain and spinal cord MRI, and enable the use of existing atlases of the brainstem compatible with the ICBM space. Copyright © 2017 Elsevier Inc. All rights reserved.
Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.

Science.gov (United States)

Maskey, Dhiraj; Kim, Hyung Gun; Suh, Myung-Whan; Roh, Gu Seob; Kim, Myeung Ju

2014-08-01

The increasing use of mobile communication has triggered an interest in its possible effects on the regulation of neurotransmitter signals. Due to the close proximity of mobile phones to hearing-related brain regions during usage, its use may lead to a decrease in the ability to segregate sounds, leading to serious auditory dysfunction caused by the prolonged exposure to radiofrequency (RF) radiation. The interplay among auditory processing, excitation and inhibitory molecule interactions plays a major role in auditory function. In particular, inhibitory molecules, such a glycine, are predominantly localized in the auditory brainstem. However, the effects of exposure to RF radiation on auditory function have not been reported to date. Thus, the aim of the present study was to investigate the effects of exposure to RF radiation on glycine receptor (GlyR) immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific absorption rate of 4.0 W/kg for three months using free-floating immunohistochemistry. Compared with the sham control (SC) group, a significant loss of staining intensity of neuropils and cells in the different subdivisions of the auditory brainstem regions was observed in the mice exposed to RF radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was also noted in the cochlear nuclear complex [anteroventral cochlear nucleus (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR) analysis also revealed a significant threshold elevation of in the exposed (E4) group, which may be associated with auditory dysfunction. The present study suggests that the auditory brainstem region
Binaural interaction in the auditory brainstem response: a normative study.

Science.gov (United States)

Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Battmer, Rolf-Dieter; Dhooge, Ingeborg J M

2015-04-01

Binaural interaction can be investigated using auditory evoked potentials. A binaural interaction component can be derived from the auditory brainstem response (ABR-BIC) and is considered evidence for binaural interaction at the level of the brainstem. Although click ABR-BIC has been investigated thoroughly, data on 500 Hz tone-burst (TB) ABR-BICs are scarce. In this study, characteristics of click and 500 Hz TB ABR-BICs are described. Furthermore, reliability of both click and 500 Hz TB ABR-BIC are investigated. Eighteen normal hearing young adults (eight women, ten men) were included. ABRs were recorded in response to clicks and 500 Hz TBs. ABR-BICs were derived by subtracting the binaural response from the sum of the monaural responses measured in opposite ears. Good inter-rater reliability is obtained for both click and 500 Hz TB ABR-BICs. The most reliable peak in click ABR-BIC occurs at a mean latency of 6.06 ms (SD 0.354 ms). Reliable 500 Hz TB ABR-BIC are obtained with a mean latency of 9.47 ms (SD 0.678 ms). Amplitudes are larger for 500 Hz TB ABR-BIC than for clicks. The most reliable peak in click ABR-BIC occurs at the downslope of wave V. Five hundred Hertz TB ABR-BIC is characterized by a broad positivity occurring at the level of wave V. The ABR-BIC is a useful technique to investigate binaural interaction in certain populations. Examples are bilateral hearing aid users, bilateral cochlear implant users and bimodal listeners. The latter refers to the combination of unilateral cochlear implantation and contralateral residual hearing. The majority of these patients have residual hearing in the low frequencies. The current study suggests that 500 Hz TB ABR-BIC may be a suitable technique to assess binaural interaction in this specific population of cochlear implant users. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
The Monoamine Brainstem Reticular Formation as a Paradigm for Re-Defining Various Phenotypes of Parkinson’s Disease Owing Genetic and Anatomical Specificity

Science.gov (United States)

Gambardella, Stefano; Ferese, Rosangela; Biagioni, Francesca; Busceti, Carla L.; Campopiano, Rosa; Griguoli, Anna M. P.; Limanaqi, Fiona; Novelli, Giuseppe; Storto, Marianna; Fornai, Francesco

2017-01-01

The functional anatomy of the reticular formation (RF) encompasses a constellation of brain regions which are reciprocally connected to sub-serve a variety of functions. Recent evidence indicates that neuronal degeneration within one of these regions spreads synaptically along brainstem circuitries. This is exemplified by the recruitment of various brainstem reticular nuclei in specific Parkinson’s disease (PD) phenotypes, and by retrospective analysis of lethargic post-encephalitic parkinsonism. In fact, the spreading to various monoamine reticular nuclei can be associated with occurrence of specific motor and non-motor symptoms (NMS). This led to re-consider PD as a brainstem monoamine disorder (BMD). This definition surpasses the anatomy of meso-striatal motor control to include a variety of non-motor domains. This concept clearly emerges from the quite specific clinical-anatomical correlation which can be drawn in specific paradigms of PD genotypes. Therefore, this review article focuses on the genetics and neuroanatomy of three PD genotypes/phenotypes which can be selected as prototype paradigms for a differential recruitment of the RF leading to differential occurrence of NMS: (i) Parkin-PD, where NMS are rarely reported; (ii) LRRK2-PD and slight SNC point mutations, where the prevalence of NMS resembles idiopathic PD; (iii) Severe SNCA point mutations and multiplications, where NMS are highly represented. PMID:28458632
Overexpression of the NR2A subunit in the forebrain impairs long-term social recognition and non-social olfactory memory.

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Jacobs, S A; Tsien, J Z

2014-04-01

Animals must recognize and remember conspecifics and potential mates, and distinguish these animals from potential heterospecific competitors and predators. Despite its necessity, aged animals are known to exhibit impaired social recognition memory. As the brain ages, the ratio of NR2A:NR2B in the brain increases over time and has been postulated to underlie the cognitive decline observed during the aging process. Here, we test the hypothesis that an increased NR2A:NR2B subunit ratio underlies long-term social recognition memory. Using transgenic overexpression of NR2A in the forebrain regions, we investigated the ability of these mice to learn and remember male and female conspecifics, mice of another strain and animals of another rodent species, the rat. Furthermore, due to the importance of olfaction in social recognition, we tested the olfactory memory in the NR2A transgenic mice. Our series of behavioral experiments revealed significant impairments in the NR2A transgenic mice in long-term social memory of both male and female conspecifics. Additionally, the NR2A transgenic mice are unable to recognize mice of another strain or rats. The NR2A transgenic mice also exhibited long-term memory impairments in the olfactory recognition task. Taken together, our results provide evidence that an increased NR2A:NR2B ratio in the forebrain leads to reduced long-term memory function, including the ethologically important memories such as social recognition and olfactory memory.
Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits

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Miriam Annika Vogt

2014-11-01

Full Text Available The cyclic AMP (cAMP-response element binding protein (CREB is an activity-dependent transcription factor playing a role in synaptic plasticity, learning and memory, and emotional behavior. However, the impact of Creb ablation on rodent behavior is vague as e.g. memory performance of different Creb mutant mice depends on the specific type of mutation per se but additionally on the background and learning protocol differences. Here we present the first targeted ablation of CREB induced during adulthood selectively in principal forebrain neurons in a pure background strain of C57BL/6 mice. All hippocampal principal neurons exhibited lack of CREB expression. Mutant mice showed a severe anxiety phenotype in the openfield and novel object exploration test as well as in the Dark-Light Box Test, but unaltered hippocampus-dependent long-term memory in the Morris water maze and in context dependent fear conditioning. On the molecular level, CREB ablation led to CREM up regulation in the hippocampus and frontal cortex which may at least in part compensate for the loss of CREB. BDNF, a postulated CREB target gene, was down regulated in the frontal lobe but not in the hippocampus; neurogenesis remained unaltered. Our data indicate that in the adult mouse forebrain the late onset of CREB ablation can, in case of memory functionality, be compensated for and is not essential for memory consolidation and retrieval during adulthood. In contrast, the presence of CREB protein during adulthood seems to be pivotal for the regulation of emotional behavior.
Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism-associated MET receptor tyrosine kinase.

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Kamitakahara, Anna; Wu, Hsiao-Huei; Levitt, Pat

2017-12-15

Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a MET EGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD. © 2017 Wiley Periodicals, Inc.
Surgical outcome of motor deficits and neurological status in brainstem cavernous malformations based on preoperative diffusion tensor imaging: a prospective randomized clinical trial.

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Li, Da; Jiao, Yu-Ming; Wang, Liang; Lin, Fu-Xin; Wu, Jun; Tong, Xian-Zeng; Wang, Shuo; Cao, Yong

2018-03-16

OBJECTIVE Surgical management of brainstem lesions is challenging due to the highly compact, eloquent anatomy of the brainstem. This study aimed to evaluate the safety and efficacy of preoperative diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in brainstem cavernous malformations (CMs). METHODS A prospective randomized controlled clinical trial was performed by using stratified blocked randomization. The primary eligibility criterion of the study was being a surgical candidate for brainstem CMs (with informed consent). The study enrolled 23 patients who underwent preoperative DTI/DTT and 24 patients who did not (the control group). The pre- and postoperative muscle strength of both limbs and modified Rankin Scale (mRS) scores were evaluated. Muscle strength of any limb at 12 months after surgery at the clinic visit was the primary outcome; worsened muscle strength was considered to be a poor outcome. Outcome assessors were blinded to patient management. This study reports the preliminary results of the interim analysis. RESULTS The cohort included 47 patients (22 women) with a mean age of 35.7 years. The clinical baselines between these 2 groups were not significantly different. In the DTI/DTT group, the corticospinal tract was affected in 17 patients (73.9%): it was displaced, deformed/partially interrupted, or completely interrupted in 6, 7, and 4 patients, respectively. The surgical approach and brainstem entry point were adjusted in 3 patients (13.0%) based on DTI/DTT data. The surgical morbidity of the DTI/DTT group (7/23, 30.4%) was significantly lower than that of the control group (19/24, 79.2%, p = 0.001). At 12 months, the mean mRS score (1.1, p = 0.034) and percentage of patients with worsened motor deficits (4.3%, p = 0.006) were significantly lower in the DTI/DTT group than in the control group (1.7% and 37.5%). Multivariate logistic regression identified the absence of preoperative DTI/DTT (OR 0.06, 95% CI 0.01-0.73, p = 0
Thresholds of Tone Burst Auditory Brainstem Responses for Infants and Young Children with Normal Hearing in Taiwan

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Chung-Yi Lee

2007-10-01

Conclusion: Based on the published research and our study, we suggest setting the normal criterion levels for infants and young children in Taiwan of the tone burst auditory brainstem response to air-conducted tones as 30 dB nHL for 500 and 1000 Hz, and 25 dB nHL for 2000 and 4000 Hz.
Mechanisms of spectral and temporal integration in the mustached bat inferior colliculus

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Wenstrup, Jeffrey James; Nataraj, Kiran; Sanchez, Jason Tait

2012-01-01

This review describes mechanisms and circuitry underlying combination-sensitive response properties in the auditory brainstem and midbrain. Combination-sensitive neurons, performing a type of auditory spectro-temporal integration, respond to specific, properly timed combinations of spectral elements in vocal signals and other acoustic stimuli. While these neurons are known to occur in the auditory forebrain of many vertebrate species, the work described here establishes their origin in the auditory brainstem and midbrain. Focusing on the mustached bat, we review several major findings: (1) Combination-sensitive responses involve facilitatory interactions, inhibitory interactions, or both when activated by distinct spectral elements in complex sounds. (2) Combination-sensitive responses are created in distinct stages: inhibition arises mainly in lateral lemniscal nuclei of the auditory brainstem, while facilitation arises in the inferior colliculus (IC) of the midbrain. (3) Spectral integration underlying combination-sensitive responses requires a low-frequency input tuned well below a neuron's characteristic frequency (ChF). Low-ChF neurons in the auditory brainstem project to high-ChF regions in brainstem or IC to create combination sensitivity. (4) At their sites of origin, both facilitatory and inhibitory combination-sensitive interactions depend on glycinergic inputs and are eliminated by glycine receptor blockade. Surprisingly, facilitatory interactions in IC depend almost exclusively on glycinergic inputs and are largely independent of glutamatergic and GABAergic inputs. (5) The medial nucleus of the trapezoid body (MNTB), the lateral lemniscal nuclei, and the IC play critical roles in creating combination-sensitive responses. We propose that these mechanisms, based on work in the mustached bat, apply to a broad range of mammals and other vertebrates that depend on temporally sensitive integration of information across the audible spectrum. PMID:23109917

Outer brain barriers in rat and human development

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Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

2015-01-01

Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...
Salivary peptide tyrosine-tyrosine 3-36 modulates ingestive behavior without inducing taste aversion.

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Hurtado, Maria D; Sergeyev, Valeriy G; Acosta, Andres; Spegele, Michael; La Sala, Michael; Waler, Nickolas J; Chiriboga-Hurtado, Juan; Currlin, Seth W; Herzog, Herbert; Dotson, Cedrick D; Gorbatyuk, Oleg S; Zolotukhin, Sergei

2013-11-20

Hormone peptide tyrosine-tyrosine (PYY) is secreted into circulation from the gut L-endocrine cells in response to food intake, thus inducing satiation during interaction with its preferred receptor, Y2R. Clinical applications of systemically administered PYY for the purpose of reducing body weight were compromised as a result of the common side effect of visceral sickness. We describe here a novel approach of elevating PYY in saliva in mice, which, although reliably inducing strong anorexic responses, does not cause aversive reactions. The augmentation of salivary PYY activated forebrain areas known to mediate feeding, hunger, and satiation while minimally affecting brainstem chemoreceptor zones triggering nausea. By comparing neuronal pathways activated by systemic versus salivary PYY, we identified a metabolic circuit associated with Y2R-positive cells in the oral cavity and extending through brainstem nuclei into hypothalamic satiety centers. The discovery of this alternative circuit that regulates ingestive behavior without inducing taste aversion may open the possibility of a therapeutic application of PYY for the treatment of obesity via direct oral application.
ESTROGEN RECEPTOR-alpha IMMUNOREACTIVE NEURONS IN THE BRAINSTEM AND SPINAL CORD OF THE FEMALE RHESUS MONKEY : SPECIES-SPECIFIC CHARACTERISTICS

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Vanderhorst, V. G. J. M.; Terasawa, E.; Ralston, H. J.

2009-01-01

The distribution pattern of estrogen receptors in the rodent CNS has been reported extensively, but mapping of estrogen receptors in primates is incomplete. In this study we describe the distribution of estrogen receptor alpha immunoreactive (ER-alpha 1R) neurons in the brainstem and spinal cord of
Brainstem auditory evoked potentials with the use of acoustic clicks and complex verbal sounds in young adults with learning disabilities.

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Kouni, Sophia N; Giannopoulos, Sotirios; Ziavra, Nausika; Koutsojannis, Constantinos

2013-01-01

Acoustic signals are transmitted through the external and middle ear mechanically to the cochlea where they are transduced into electrical impulse for further transmission via the auditory nerve. The auditory nerve encodes the acoustic sounds that are conveyed to the auditory brainstem. Multiple brainstem nuclei, the cochlea, the midbrain, the thalamus, and the cortex constitute the central auditory system. In clinical practice, auditory brainstem responses (ABRs) to simple stimuli such as click or tones are widely used. Recently, complex stimuli or complex auditory brain responses (cABRs), such as monosyllabic speech stimuli and music, are being used as a tool to study the brainstem processing of speech sounds. We have used the classic 'click' as well as, for the first time, the artificial successive complex stimuli 'ba', which constitutes the Greek word 'baba' corresponding to the English 'daddy'. Twenty young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) comprised the diseased group. Twenty sex-, age-, education-, hearing sensitivity-, and IQ-matched normal subjects comprised the control group. Measurements included the absolute latencies of waves I through V, the interpeak latencies elicited by the classical acoustic click, the negative peak latencies of A and C waves, as well as the interpeak latencies of A-C elicited by the verbal stimulus 'baba' created on a digital speech synthesizer. The absolute peak latencies of waves I, III, and V in response to monoaural rarefaction clicks as well as the interpeak latencies I-III, III-V, and I-V in the dyslexic subjects, although increased in comparison with normal subjects, did not reach the level of a significant difference (pwave C and the interpeak latencies of A-C elicited by verbal stimuli were found to be increased in the dyslexic group in comparison with the control group (p=0.0004 and p=0.045, respectively). In the subgroup consisting of 10 patients suffering from
Visual cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon

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Nightingale, S. (Royal Victoria Infirmary, Newcastle upon Tyne (UK)); Schofield, I.S.; Dawes, P.J.D.K. (Newcastle upon Tyne Univ. (UK). Newcastle General Hospital)

1984-01-01

Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon during radiotherapy in and around the middle ear, and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings.
Guillain-Barré Syndrome with Absent Brainstem Reflexes: a Case Report

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Susana Gordon Chaves

2014-02-01

Full Text Available A 41-year-old man was admitted to an intensive care unit following respiratory arrest. One day prior to admission, he had complaints of nausea and pain involving lower limbs. On the night of admission he developed diplopia, dysphagia, and rapidly progressive quadriparesis. He developed respiratory failure requiring mechanical lung ventilation 24 hours later. On the fifth day of hospital stay the patient became comatose with absent brainstem reflexes and appeared to be brain dead. The cerebrospinal fluid showed albuminocytological dissociation. The electroencephalogram revealed an alpha rhythmical activity. The electrophysiological evaluation revealed an inexcitability of all nerves. Guillain-Barré syndrome was suspected. With supportive treatment the patient had a remarkable recovery and now is able to independently conduct his daily activities.
Age-related hearing loss in dogs : Diagnosis with Brainstem-Evoked Response Audiometry and Treatment with Vibrant Soundbridge Middle Ear Implant.

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ter Haar, G.

2009-01-01

Age-related hearing loss (ARHL) is the most common cause of acquired hearing impairment in dogs. Diagnosis requires objective electrophysiological tests (brainstem evoked response audiometry [BERA]) evaluating the entire audible frequency range in dogs. In our laboratory a method was developed to
A new strategic neurosurgical planning tool for brainstem cavernous malformations using interactive computer graphics with multimodal fusion images.

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Kin, Taichi; Nakatomi, Hirofumi; Shojima, Masaaki; Tanaka, Minoru; Ino, Kenji; Mori, Harushi; Kunimatsu, Akira; Oyama, Hiroshi; Saito, Nobuhito

2012-07-01

In this study, the authors used preoperative simulation employing 3D computer graphics (interactive computer graphics) to fuse all imaging data for brainstem cavernous malformations. The authors evaluated whether interactive computer graphics or 2D imaging correlated better with the actual operative field, particularly in identifying a developmental venous anomaly (DVA). The study population consisted of 10 patients scheduled for surgical treatment of brainstem cavernous malformations. Data from preoperative imaging (MRI, CT, and 3D rotational angiography) were automatically fused using a normalized mutual information method, and then reconstructed by a hybrid method combining surface rendering and volume rendering methods. With surface rendering, multimodality and multithreshold techniques for 1 tissue were applied. The completed interactive computer graphics were used for simulation of surgical approaches and assumed surgical fields. Preoperative diagnostic rates for a DVA associated with brainstem cavernous malformation were compared between conventional 2D imaging and interactive computer graphics employing receiver operating characteristic (ROC) analysis. The time required for reconstruction of 3D images was 3-6 hours for interactive computer graphics. Observation in interactive mode required approximately 15 minutes. Detailed anatomical information for operative procedures, from the craniotomy to microsurgical operations, could be visualized and simulated three-dimensionally as 1 computer graphic using interactive computer graphics. Virtual surgical views were consistent with actual operative views. This technique was very useful for examining various surgical approaches. Mean (±SEM) area under the ROC curve for rate of DVA diagnosis was significantly better for interactive computer graphics (1.000±0.000) than for 2D imaging (0.766±0.091; pcomputer graphics than with 2D images. Interactive computer graphics was also useful in helping to plan the surgical
Electroretinogram (ERG) to photic stimuli should be carefully distinct from photic brainstem reflex in patients with deep coma.

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Mitsuhashi, Masahiro; Hitomi, Takefumi; Aoyama, Akihiro; Kaido, Toshimi; Ikeda, Akio; Takahashi, Ryosuke

2017-08-31

Patient 1: A 35-year-old woman became deep coma because of intracranial hemorrhage after pulmonary surgery. Patient 2: A 39-year-old woman became deep coma because of cerebellar hemorrhage after hepatic surgery. Scalp-recorded digital electroencephalography (EEG) showed electrocerebral inactivity in both cases. In addition, both EEG showed repetitive discharges at bilateral frontopolar electrodes in response to photic stimuli. The amplitude and latency of the discharges was 17 μV and 24 msec in case 1, and 9 μV and 27 msec in case 2 respectively. The activity at left frontopolar electrode disappeared after coverage of the ipsilateral eye. Based on these findings, we could exclude the possibility of brainstem response and judged it as electroretinogram (ERG). Photic stimulation is a useful activation method in EEG recording, and we can also evaluate brainstem function by checking photic blink reflex if it is evoked. However, we should be cautious about the distinction of ERG from photic blink reflex when brain death is clinically suspected.
Abnormal auditory forward masking pattern in the brainstem response of individuals with Asperger syndrome

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Johan Källstrand

2010-05-01

Full Text Available Johan Källstrand1, Olle Olsson2, Sara Fristedt Nehlstedt1, Mia Ling Sköld1, Sören Nielzén21SensoDetect AB, Lund, Sweden; 2Department of Clinical Neuroscience, Section of Psychiatry, Lund University, Lund, SwedenAbstract: Abnormal auditory information processing has been reported in individuals with autism spectrum disorders (ASD. In the present study auditory processing was investigated by recording auditory brainstem responses (ABRs elicited by forward masking in adults diagnosed with Asperger syndrome (AS. Sixteen AS subjects were included in the forward masking experiment and compared to three control groups consisting of healthy individuals (n = 16, schizophrenic patients (n = 16 and attention deficit hyperactivity disorder patients (n = 16, respectively, of matching age and gender. The results showed that the AS subjects exhibited abnormally low activity in the early part of their ABRs that distinctly separated them from the three control groups. Specifically, wave III amplitudes were significantly lower in the AS group than for all the control groups in the forward masking condition (P < 0.005, which was not the case in the baseline condition. Thus, electrophysiological measurements of ABRs to complex sound stimuli (eg, forward masking may lead to a better understanding of the underlying neurophysiology of AS. Future studies may further point to specific ABR characteristics in AS individuals that separate them from individuals diagnosed with other neurodevelopmental diseases.Keywords: asperger syndrome, auditory brainstem response, forward masking, psychoacoustics
Relationship between structural brainstem and brain plasticity and lower-limb training in spinal cord injury: a longitudinal pilot study

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Michael eVilliger

2015-05-01

Full Text Available Rehabilitative training has shown to improve significantly motor outcomes and functional walking capacity in patients with incomplete spinal cord injury (iSCI. However, whether performance improvements during rehabilitation relate to brain plasticity or whether it is based on functional adaptation of movement strategies remain uncertain. This study assessed training improvement-induced structural brain plasticity in chronic iSCI patients using longitudinal MRI.We used tensor-based morphometry (TBM to analyze longitudinal brain volume changes associated with intensive virtual reality (VR-augmented lower limb training in nine traumatic iSCI patients. The MRI data was acquired before and after a 4-week training period (16-20 training sessions. Before training, voxel-based morphometry (VBM and voxel-based cortical thickness (VBCT assessed baseline morphometric differences in nine iSCI patients compared to 14 healthy controls. The intense VR-augmented training of limb control improved significantly balance, walking speed, ambulation, and muscle strength in patients. Retention of clinical improvements was confirmed by the 3-4 months follow-up. In patients relative to controls, reductions in VBM of white matter volume within the brainstem and cerebellum and VBCT showed cortical thinning in the primary motor cortex. Over time, TBM revealed significant improvement-induced increases in the left middle temporal and occipital gyrus, left temporal pole and fusiform gyrus, both hippocampi, cerebellum, corpus callosum, and brainstem in iSCI patients. This study demonstrates structural plasticity at the cortical and brainstem level as a consequence of VR-augmented training in iSCI patients. These structural changes may serve as neuroimaging biomarkers of VR-augmented lower limb neurorehabilitation in addition to performance measures to detect improvements in rehabilitative training.
Relationship between structural brainstem and brain plasticity and lower-limb training in spinal cord injury: a longitudinal pilot study

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Villiger, Michael; Grabher, Patrick; Hepp-Reymond, Marie-Claude; Kiper, Daniel; Curt, Armin; Bolliger, Marc; Hotz-Boendermaker, Sabina; Kollias, Spyros; Eng, Kynan; Freund, Patrick

2015-01-01

Rehabilitative training has shown to improve significantly motor outcomes and functional walking capacity in patients with incomplete spinal cord injury (iSCI). However, whether performance improvements during rehabilitation relate to brain plasticity or whether it is based on functional adaptation of movement strategies remain uncertain. This study assessed training improvement-induced structural brain plasticity in chronic iSCI patients using longitudinal MRI. We used tensor-based morphometry (TBM) to analyze longitudinal brain volume changes associated with intensive virtual reality (VR)-augmented lower limb training in nine traumatic iSCI patients. The MRI data was acquired before and after a 4-week training period (16–20 training sessions). Before training, voxel-based morphometry (VBM) and voxel-based cortical thickness (VBCT) assessed baseline morphometric differences in nine iSCI patients compared to 14 healthy controls. The intense VR-augmented training of limb control improved significantly balance, walking speed, ambulation, and muscle strength in patients. Retention of clinical improvements was confirmed by the 3–4 months follow-up. In patients relative to controls, VBM revealed reductions of white matter volume within the brainstem and cerebellum and VBCT showed cortical thinning in the primary motor cortex. Over time, TBM revealed significant improvement-induced volume increases in the left middle temporal and occipital gyrus, left temporal pole and fusiform gyrus, both hippocampi, cerebellum, corpus callosum, and brainstem in iSCI patients. This study demonstrates structural plasticity at the cortical and brainstem level as a consequence of VR-augmented training in iSCI patients. These structural changes may serve as neuroimaging biomarkers of VR-augmented lower limb neurorehabilitation in addition to performance measures to detect improvements in rehabilitative training. PMID:25999842
The role of eABR with intracochlear test electrode in decision making between cochlear and brainstem implants: preliminary results.

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Cinar, Betul Cicek; Yarali, Mehmet; Atay, Gamze; Bajin, Munir Demir; Sennaroglu, Gonca; Sennaroglu, Levent

2017-09-01

The objective of the study was to discuss the findings of intraoperative electrically evoked auditory brainstem response (eABR) test results with a recently designed intracochlear test electrode (ITE) in terms of their relation to decisions of cochlear or auditory brainstem implantation. This clinical study was conducted in Hacettepe University, Department of Otolaryngology, Head and Neck Surgery and Department of Audiology. Subjects were selected from inner ear malformation (IEM) database. Eleven subjects with profound sensorineural hearing loss were included in the current study with age range from 1 year 3 months to 4 years 3 months for children with prelingual hearing loss. There was only one 42-year-old post-lingual subject. eABR was recorded with an ITE and intraoperatively with an original cochlear implant (CI) electrode in 11 cases with different IEMs. Findings of eABR with ITE and their relation to the decision for CI or auditory brainstem implant (ABI) are discussed. Positive eABR test results were found to be dependent on close to normal cochlear structures and auditory nerve. The probability of positive result decreases with increasing degree of malformation severity. The prediction value of eABR via ITE on decision for hearing restoration was found to be questionable in this study. The results of eABR with ITE have predictive value on what we will get with the actual CI electrode. ITE appears to stimulate the cochlea like an actual CI. If the eABR is positive, the results are reliable. However, if eABR is negative, the results should be evaluated with preoperative audiological testing and MRI findings.
Studying respiratory rhythm generation in a developing bird: Hatching a new experimental model using the classic in vitro brainstem-spinal cord preparation.

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Vincen-Brown, Michael A; Whitesitt, Kaitlyn C; Quick, Forrest G; Pilarski, Jason Q

2016-04-01

It has been more than thirty years since the in vitro brainstem-spinal cord preparation was first presented as a method to study automatic breathing behaviors in the neonatal rat. This straightforward preparation has led to an incredible burst of information about the location and coordination of several spontaneously active microcircuits that form the ventrolateral respiratory network of the brainstem. Despite these advances, our knowledge of the mechanisms that regulate central breathing behaviors is still incomplete. Investigations into the nature of spontaneous breathing rhythmicity have almost exclusively focused on mammals, and there is a need for comparative experimental models to evaluate several unresolved issues from a different perspective. With this in mind, we sought to develop a new avian in vitro model with the long term goal to better understand questions associated with the ontogeny of respiratory rhythm generation, neuroplasticity, and whether multiple, independent oscillators drive the major phases of breathing. The fact that birds develop in ovo provides unparalleled access to central neuronal networks throughout the prenatal period - from embryo to hatchling - that are free from confounding interactions with mother. Previous studies using in vitro avian models have been strictly limited to the early embryonic period. Consequently, the details and even the presence of brainstem derived breathing-related rhythmogenesis in birds have never been described. In the present study, we used the altricial zebra finch (Taeniopygia guttata) and show robust spontaneous motor outflow through cranial motor nerve IX, which is first detectable on embryonic day four and continues through prenatal and early postnatal development without interruption. We also show that brainstem oscillations change dramatically over the course of prenatal development, sometimes within hours, which suggests rapid maturational modifications in growth and connectivity. We propose
Transcriptional Profiling of Cholinergic Neurons From Basal Forebrain Identifies Changes in Expression of Genes Between Sleep and Wake.

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Nikonova, Elena V; Gilliland, Jason DA; Tanis, Keith Q; Podtelezhnikov, Alexei A; Rigby, Alison M; Galante, Raymond J; Finney, Eva M; Stone, David J; Renger, John J; Pack, Allan I; Winrow, Christopher J

2017-06-01

To assess differences in gene expression in cholinergic basal forebrain cells between sleeping and sleep-deprived mice sacrificed at the same time of day. Tg(ChAT-eGFP)86Gsat mice expressing enhanced green fluorescent protein (eGFP) under control of the choline acetyltransferase (Chat) promoter were utilized to guide laser capture of cholinergic cells in basal forebrain. Messenger RNA expression levels in these cells were profiled using microarrays. Gene expression in eGFP(+) neurons was compared (1) to that in eGFP(-) neurons and to adjacent white matter, (2) between 7:00 am (lights on) and 7:00 pm (lights off), (3) between sleep-deprived and sleeping animals at 0, 3, 6, and 9 hours from lights on. There was a marked enrichment of ChAT and other markers of cholinergic neurons in eGFP(+) cells. Comparison of gene expression in these eGFP(+) neurons between 7:00 am and 7:00 pm revealed expected differences in the expression of clock genes (Arntl2, Per1, Per2, Dbp, Nr1d1) as well as mGluR3. Comparison of expression between spontaneous sleep and sleep-deprived groups sacrificed at the same time of day revealed a number of transcripts (n = 55) that had higher expression in sleep deprivation compared to sleep. Genes upregulated in sleep deprivation predominantly were from the protein folding pathway (25 transcripts, including chaperones). Among 42 transcripts upregulated in sleep was the cold-inducible RNA-binding protein. Cholinergic cell signatures were characterized. Whether the identified genes are changing as a consequence of differences in behavioral state or as part of the molecular regulatory mechanism remains to be determined. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.
Salvinorin A preserves cerebral pial artery autoregulation after forebrain ischemia via the PI3K/AKT/cGMP pathway

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H.P. Dong

2018-03-01

Full Text Available This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR control group received DMSO (1 µL/kg immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg and LY294002 (10 µM, L-NAME (10 μM, or norbinaltorphimine (norBIN, 1 μM after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF were also measured. The phosphorylation of AKT (p-AKT was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.
Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex.

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Okabe, Naohiko; Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.
Visual cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon

International Nuclear Information System (INIS)

Nightingale, S.; Schofield, I.S.; Dawes, P.J.D.K.

1984-01-01

Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon during radiotherapy in and around the middle ear, and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings. (author)
Lateralization and Binaural Interaction of Middle-Latency and Late-Brainstem Components of the Auditory Evoked Response.

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Dykstra, Andrew R; Burchard, Daniel; Starzynski, Christian; Riedel, Helmut; Rupp, Andre; Gutschalk, Alexander

2016-08-01

We used magnetoencephalography to examine lateralization and binaural interaction of the middle-latency and late-brainstem components of the auditory evoked response (the MLR and SN10, respectively). Click stimuli were presented either monaurally, or binaurally with left- or right-leading interaural time differences (ITDs). While early MLR components, including the N19 and P30, were larger for monaural stimuli presented contralaterally (by approximately 30 and 36 % in the left and right hemispheres, respectively), later components, including the N40 and P50, were larger ipsilaterally. In contrast, MLRs elicited by binaural clicks with left- or right-leading ITDs did not differ. Depending on filter settings, weak binaural interaction could be observed as early as the P13 but was clearly much larger for later components, beginning at the P30, indicating some degree of binaural linearity up to early stages of cortical processing. The SN10, an obscure late-brainstem component, was observed consistently in individuals and showed linear binaural additivity. The results indicate that while the MLR is lateralized in response to monaural stimuli-and not ITDs-this lateralization reverses from primarily contralateral to primarily ipsilateral as early as 40 ms post stimulus and is never as large as that seen with fMRI.
Physiological Characterization of Vestibular Efferent Brainstem Neurons Using a Transgenic Mouse Model

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Leijon, Sara; Magnusson, Anna K.

2014-01-01

The functional role of efferent innervation of the vestibular end-organs in the inner ear remains elusive. This study provides the first physiological characterization of the cholinergic vestibular efferent (VE) neurons in the brainstem by utilizing a transgenic mouse model, expressing eGFP under a choline-acetyltransferase (ChAT)-locus spanning promoter in combination with targeted patch clamp recordings. The intrinsic electrical properties of the eGFP-positive VE neurons were compared to the properties of the lateral olivocochlear (LOC) brainstem neurons, which gives rise to efferent innervation of the cochlea. Both VE and the LOC neurons were marked by their negative resting membrane potential neurons differed significantly in the depolarizing range. When injected with positive currents, VE neurons fired action potentials faithfully to the onset of depolarization followed by sparse firing with long inter-spike intervals. This response gave rise to a low response gain. The LOC neurons, conversely, responded with a characteristic delayed tonic firing upon depolarizing stimuli, giving rise to higher response gain than the VE neurons. Depolarization triggered large TEA insensitive outward currents with fast inactivation kinetics, indicating A-type potassium currents, in both the inner ear-projecting neuronal types. Immunohistochemistry confirmed expression of Kv4.3 and 4.2 ion channel subunits in both the VE and LOC neurons. The difference in spiking responses to depolarization is related to a two-fold impact of these transient outward currents on somatic integration in the LOC neurons compared to in VE neurons. It is speculated that the physiological properties of the VE neurons might be compatible with a wide-spread control over motion and gravity sensation in the inner ear, providing likewise feed-back amplification of abrupt and strong phasic signals from the semi-circular canals and of tonic signals from the gravito-sensitive macular organs. PMID:24867596

The selective alpha7 nicotinic acetylcholine receptor agonist A-582941 activates immediate early genes in limbic regions of the forebrain

DEFF Research Database (Denmark)

Thomsen, M S; Mikkelsen, J D; Timmermann, D B

2008-01-01

to study whether alpha7 nAChR stimulation activates brain regions involved in cognition in juvenile as well as adult individuals. Here, we compared the effects of the novel and selective alpha7 nAChR agonist 2-methyl-5-(6-phenyl-pyridazin-3-yl)-octahydro-pyrrolo[3,4-c]pyrrole (A-582941) in the juvenile...... regions critically involved in working memory and attention. Furthermore, this effect is more pronounced in juvenile than adult rats, indicating that the juvenile forebrain is more responsive to alpha7 nAChR stimulation. This observation may be relevant in the treatment of juvenile-onset schizophrenia....
Brainstem edema caused by traumatic carotid-cavernous fistula: A case report and review of the literature

OpenAIRE

YU, JINLU; GUO, YUNBAO; ZHAO, SHUJIE; XU, KAN

2015-01-01

Brainstem edema caused by traumatic carotid-cavernous fistula (TCCF) is rare, and there is little information available regarding its clinical characteristics. The present report describes the case of a 51-year-old man with TCCF, who presented with right exophthalmos and intracranial bruit for 1 week. One month prior to admission at hospital, he fractured the frontal and ethmoid sinuses. Digital subtraction angiography confirmed the diagnosis of TCCF, and magnetic resonance imaging (MRI) sugg...
Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

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Christelle Anaclet

2010-01-01

Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle
Attention-related modulation of auditory brainstem responses during contralateral noise exposure.

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Ikeda, Kazunari; Sekiguchi, Takahiro; Hayashi, Akiko

2008-10-29

As determinants facilitating attention-related modulation of the auditory brainstem response (ABR), two experimental factors were examined: (i) auditory discrimination; and (ii) contralateral masking intensity. Tone pips at 80 dB sound pressure level were presented to the left ear via either single-tone exposures or oddball exposures, whereas white noise was delivered continuously to the right ear at variable intensities (none--80 dB sound pressure level). Participants each conducted two tasks during stimulation, either reading a book (ignoring task) or detecting target tones (attentive task). Task-related modulation within the ABR range was found only during oddball exposures at contralateral masking intensities greater than or equal to 60 dB. Attention-related modulation of ABR can thus be detected reliably during auditory discrimination under contralateral masking of sufficient intensity.
Concentrated pitch discrimination modulates auditory brainstem responses during contralateral noise exposure.

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Ikeda, Kazunari; Sekiguchi, Takahiro; Hayashi, Akiko

2010-03-31

This study examined a notion that auditory discrimination is a requisite for attention-related modulation of the auditory brainstem response (ABR) during contralateral noise exposure. Given that the right ear was exposed continuously with white noise at an intensity of 60-80 dB sound pressure level, tone pips at 80 dB sound pressure level were delivered to the left ear through either single-stimulus or oddball procedures. Participants conducted reading (ignoring task) and counting target tones (attentive task) during stimulation. The oddball but not the single-stimulus procedures elicited task-related modulations in both early (ABR) and late (processing negativity) event-related potentials simultaneously. The elicitation of the attention-related ABR modulation during contralateral noise exposure is thus considered to require auditory discrimination and have the corticofugal nature evidently.
Searching for the optimal stimulus eliciting auditory brainstem responses in humans

DEFF Research Database (Denmark)

Fobel, Oliver; Dau, Torsten

2004-01-01

-chirp, was based on estimates of human basilar membrane (BM) group delays derived from stimulus-frequency otoacoustic emissions (SFOAE) at a sound pressure level of 40 dB [Shera and Guinan, in Recent Developments in Auditory Mechanics (2000)]. The other chirp, referred to as the A-chirp, was derived from latency...
The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain.

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Peng, Y; Lu, Z; Li, G; Piechowicz, M; Anderson, M; Uddin, Y; Wu, J; Qiu, S

2016-07-01

The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which has a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD.
Microbiome-Gut-Brain Axis: A Pathway for Improving Brainstem Serotonin Homeostasis and Successful Autoresuscitation in SIDS-A Novel Hypothesis.

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Praveen, Vijayakumar; Praveen, Shama

2016-01-01

Sudden infant death syndrome (SIDS) continues to be a major public health issue. Following its major decline since the "Back to Sleep" campaign, the incidence of SIDS has plateaued, with an annual incidence of about 1,500 SIDS-related deaths in the United States and thousands more throughout the world. The etiology of SIDS, the major cause of postneonatal mortality in the western world, is still poorly understood. Although sleeping in prone position is a major risk factor, SIDS continues to occur even in the supine sleeping position. The triple-risk model of Filiano and Kinney emphasizes the interaction between a susceptible infant during a critical developmental period and stressor/s in the pathogenesis of SIDS. Recent evidence ranges from dysregulated autonomic control to findings of altered neurochemistry, especially the serotonergic system that plays an important role in brainstem cardiorespiratory/thermoregulatory centers. Brainstem serotonin (5-HT) and tryptophan hydroxylase-2 (TPH-2) levels have been shown to be lower in SIDS, supporting the evidence that defects in the medullary serotonergic system play a significant role in SIDS. Pathogenic bacteria and their enterotoxins have been associated with SIDS, although no direct evidence has been established. We present a new hypothesis that the infant's gut microbiome, and/or its metabolites, by its direct effects on the gut enterochromaffin cells, stimulates the afferent gut vagal endings by releasing serotonin (paracrine effect), optimizing autoresuscitation by modulating brainstem 5-HT levels through the microbiome-gut-brain axis, thus playing a significant role in SIDS during the critical period of gut flora development and vulnerability to SIDS. The shared similarities between various risk factors for SIDS and their relationship with the infant gut microbiome support our hypothesis. Comprehensive gut-microbiome studies are required to test our hypothesis.
Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain.

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Ariana Frederick

Full Text Available Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP and Enkephalin (Enk, expressed in distinct neuronal populations throughout the forebrain. Regions examined included the limbic forebrain (dorsal striatum, nucleus accumbens, amygdala, stria terminalis, thalamus medial habenula of the thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in nearly all neurons (~90%, and PER2 was expressed in a slightly lower proportion of cells. There was no specific correlation to SubP- or Enk- expressing subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were expressed in a much smaller percentage of cells, and Enk was rarely found in the same cells that expressed the clock proteins (SubP was undetectable. These results indicate that clock genes are not unique to specific cell types, and further studies will be required to determine the factors that contribute to the regulation of clock gene expression throughout the brain.
Imaging of glial cell morphology, SOD1 distribution and elemental composition in the brainstem and hippocampus of the ALS hSOD1G93A rat.

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Stamenković, Stefan; Dučić, Tanja; Stamenković, Vera; Kranz, Alexander; Andjus, Pavle R

2017-08-15

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor and cognitive domains of the CNS. Mutations in the Cu,Zn-superoxide dismutase (SOD1) cause 20% of familial ALS and provoke formation of intracellular aggregates and copper and zinc unbinding, leading to glial activation and neurodegeneration. Therefore, we investigated glial cell morphology, intracellular SOD1 distribution, and elemental composition in the brainstem and hippocampus of the hSOD1 G93A transgenic rat model of ALS. Immunostaining for astrocytes, microglia and SOD1 revealed glial proliferation and progressive tissue accumulation of SOD1 in both brain regions of ALS rats starting already at the presymptomatic stage. Glial cell morphology analysis in the brainstem of ALS rats revealed astrocyte activation occurring before disease symptoms onset, followed by activation of microglia. Hippocampal ALS astrocytes exhibited an identical reactive profile, while microglial morphology was unchanged. Additionally, ALS brainstem astrocytes demonstrated progressive SOD1 accumulation in the cell body and processes, while microglial SOD1 levels were reduced and its distribution limited to distal cell processes. In the hippocampus both glial cell types exhibited SOD1 accumulation in the cell body. X-ray fluorescence imaging revealed decreased P and increased Ca, Cl, K, Ni, Cu and Zn in the brainstem, and higher levels of Cl, Ni and Cu, but lower levels of Zn in the hippocampus of symptomatic ALS rats. These results bring new insights into the glial response during disease development and progression in motor as well as in non-motor CNS structures, and indicate disturbed tissue elemental homeostasis as a prominent hallmark of disease pathology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei

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Reis, Renata; Hennessy, Edel; Murray, Caoimhe; Griffin, Éadaoin W.

2015-01-01

Aims The processes by which neurons degenerate in chronic neurodegenerative diseases remain unclear. Synaptic loss and axonal pathology frequently precede neuronal loss and protein aggregation demonstrably spreads along neuroanatomical pathways in many neurodegenerative diseases. The spread of neuronal pathology is less studied. Methods We previously demonstrated severe neurodegeneration in the posterior thalamus of multiple prion disease strains. Here we used the ME7 model of prion disease to examine the nature of this degeneration in the posterior thalamus and the major brainstem projections into this region. Results We objectively quantified neurological decline between 16 and 18 weeks post‐inoculation and observed thalamic subregion‐selective neuronal, synaptic and axonal pathology while demonstrating relatively uniform protease‐resistant prion protein (PrP) aggregation and microgliosis across the posterior thalamus. Novel amyloid precursor protein (APP) pathology was particularly prominent in the thalamic posterior (PO) and ventroposterior lateral (VPL) nuclei. The brainstem nuclei forming the major projections to these thalamic nuclei were examined. Massive neuronal loss in the PO was not matched by significant neuronal loss in the interpolaris (Sp5I), while massive synaptic loss in the ventral posteromedial nucleus (VPM) did correspond with significant neuronal loss in the principal trigeminal nucleus. Likewise, significant VPL synaptic loss was matched by significant neuronal loss in the gracile and cuneate nuclei. Conclusion These findings demonstrate significant spread of neuronal pathology from the thalamus to the brainstem in prion disease. The divergent neuropathological features in adjacent neuronal populations demonstrates that there are discrete pathways to neurodegeneration in different neuronal populations. PMID:25727649
Basal forebrain motivational salience signal enhances cortical processing and decision speed

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Sylvina M Raver

2015-10-01

Full Text Available The basal forebrain (BF contains major projections to the cerebral cortex, and plays a well-documented role in arousal, attention, decision-making, and in modulating cortical activity. BF neuronal degeneration is an early event in Alzheimer’s disease and dementias, and occurs in normal cognitive aging. While the BF is best known for its population of cortically projecting cholinergic neurons, the region is anatomically and neurochemically diverse, and also contains prominent populations of non-cholinergic projection neurons. In recent years, increasing attention has been dedicated to these non-cholinergic BF neurons in order to better understand how non-cholinergic BF circuits control cortical processing and behavioral performance. In this review, we focus on a unique population of putative non-cholinergic BF neurons that encodes the motivational salience of stimuli with a robust ensemble bursting response. We review recent studies that describe the specific physiological and functional characteristics of these BF salience-encoding neurons in behaving animals. These studies support the unifying hypothesis whereby BF salience-encoding neurons act as a gain modulation mechanism of the decision-making process to enhance cortical processing of behaviorally relevant stimuli, and thereby facilitate faster and more precise behavioral responses. This function of BF salience-encoding neurons represents a critical component in determining which incoming stimuli warrant an animal’s attention, and is therefore a fundamental and early requirement of behavioral flexibility.
MR measurement of normal brainstem cerebellum and corpus callosum on midsagittal section

International Nuclear Information System (INIS)

Kogame, Saeko; Sawa, S.; Inoue, Yuichi; Fukuda, Teruo; Tada, Takuji; Shakudo, Miyuki; Yahata, Kunifumi; Shimizu, Hiroshi; Onoyama, Yasuhito.

1989-01-01

The dimensions of the brainstem, cerebellum and corpus callosum were measured on magnetic resonance (MR) images with sagittal spin-echo sequence. Eighty-two normal adults (average 49.6 years old) were measured. The mesencephalic, pontine or cerebellar diamaters and lengths could be measured more accurately and reproducibly than medullary diameter and length. The anterio-posterior diameter of the pons and the cerebellum was 23.2±1.4 mm and 26.4±2.5 mm respectively. The length of the pons and the cerebellum was 27.8±2 mm and 45.8±3.5 mm respectively. We have observed focal thinning at the body of corpus callosum in 73%. This narrowing is almost unquestionably a normal variant. (author)
Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice.

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Hotta, Harumi; Uchida, Sae; Kagitani, Fusako; Maruyama, Naoki

2011-05-01

We examined whether activity of the nucleus basalis of Meynert (NBM) regulates regional cerebral cortical blood flow (rCBF) in mice, using laser speckle and laser Doppler flowmetry. In anesthetized mice, unilateral focal stimulation, either electrical or chemical, of the NBM increased rCBF of the ipsilateral cerebral cortex in the frontal, parietal and occipital lobes, independent of changes in systemic blood pressure. Most of vasodilative responses to low intensity stimuli (2 times threshold intensity: 2T) were abolished by atropine (a muscarinic cholinergic blocker), whereas responses to higher intensity stimuli (3T) were abolished by atropine and mecamylamine (a nicotinic cholinergic blocker). Blood flow changes were largest when the tip of the electrode was located within the area containing cholinergic neurons shown by choline acetyltransferase-immunocytochemistry. These results suggest that cholinergic projections from basal forebrain neurons in mice cause vasodilation in the ipsilateral cerebral cortex by a combination of muscarinic and nicotinic mechanisms, as previously found in rats and cats.
The amygdala and basal forebrain as a pathway for motivationally guided attention.

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Peck, Christopher J; Salzman, C Daniel

2014-10-08

Visual stimuli associated with rewards attract spatial attention. Neurophysiological mechanisms that mediate this process must register both the motivational significance and location of visual stimuli. Recent neurophysiological evidence indicates that the amygdala encodes information about both of these parameters. Furthermore, the firing rate of amygdala neurons predicts the allocation of spatial attention. One neural pathway through which the amygdala might influence attention involves the intimate and bidirectional connections between the amygdala and basal forebrain (BF), a brain area long implicated in attention. Neurons in the rhesus monkey amygdala and BF were therefore recorded simultaneously while subjects performed a detection task in which the stimulus-reward associations of visual stimuli modulated spatial attention. Neurons in BF were spatially selective for reward-predictive stimuli, much like the amygdala. The onset of reward-predictive signals in each brain area suggested different routes of processing for reward-predictive stimuli appearing in the ipsilateral and contralateral fields. Moreover, neurons in the amygdala, but not BF, tracked trial-to-trial fluctuations in spatial attention. These results suggest that the amygdala and BF could play distinct yet inter-related roles in influencing attention elicited by reward-predictive stimuli. Copyright © 2014 the authors 0270-6474/14/3413757-11$15.00/0.
Working memory capacity and visual-verbal cognitive load modulate auditory-sensory gating in the brainstem: toward a unified view of attention.

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Sörqvist, Patrik; Stenfelt, Stefan; Rönnberg, Jerker

2012-11-01

Two fundamental research questions have driven attention research in the past: One concerns whether selection of relevant information among competing, irrelevant, information takes place at an early or at a late processing stage; the other concerns whether the capacity of attention is limited by a central, domain-general pool of resources or by independent, modality-specific pools. In this article, we contribute to these debates by showing that the auditory-evoked brainstem response (an early stage of auditory processing) to task-irrelevant sound decreases as a function of central working memory load (manipulated with a visual-verbal version of the n-back task). Furthermore, individual differences in central/domain-general working memory capacity modulated the magnitude of the auditory-evoked brainstem response, but only in the high working memory load condition. The results support a unified view of attention whereby the capacity of a late/central mechanism (working memory) modulates early precortical sensory processing.
Deletion of beta-2-microglobulin ameliorates spinal cord lesion load and promotes recovery of brainstem NAA levels in a murine model of multiple sclerosis.

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Denic, Aleksandar; Pirko, Istvan; Wootla, Bharath; Bieber, Allan; Macura, Slobodan; Rodriguez, Moses

2012-09-01

We used genetic deletion of β2-microglobulin to study the influence of CD8(+) T cells on spinal cord demyelination, remyelination, axonal loss and brainstem N-acetyl aspartate levels during the acute and chronic phases of Theiler's murine encephalomyelitis virus (TMEV) infection. We used β2m(-/-) and β2m(+/+) B10.Q mice (of H-2(q) background) normally susceptible to TMEV-induced demyelination. Over the disease course, β2m(+/+) mice had increasing levels of demyelination and minimal late-onset remyelination. In contrast, β2m(-/-) mice had steady levels of demyelination from 45-390 dpi and remyelination was extensive and more complete. Early in the disease, brainstem NAA levels drop in both strains, but accordingly with remyelination and axonal preservation, NAA recover in β2m(-/-) mice despite equivalent brainstem pathology. At 270 dpi, β2m(+/+) mice had significantly fewer spinal cord axons than β2m(-/-) mice (up to 28% less). In addition, β2m(+/+) mice lost axons of all calibers, whereas β2m(-/-) mice had a modest loss of only medium- and large-caliber axons. This study further supports the hypothesis that CD8(+) T cells are involved in demyelination, and axonal loss following Theiler's virus-induced demyelination. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.
Basal forebrain projections to the lateral habenula modulate aggression reward.

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Golden, Sam A; Heshmati, Mitra; Flanigan, Meghan; Christoffel, Daniel J; Guise, Kevin; Pfau, Madeline L; Aleyasin, Hossein; Menard, Caroline; Zhang, Hongxing; Hodes, Georgia E; Bregman, Dana; Khibnik, Lena; Tai, Jonathan; Rebusi, Nicole; Krawitz, Brian; Chaudhury, Dipesh; Walsh, Jessica J; Han, Ming-Hu; Shapiro, Matt L; Russo, Scott J

2016-06-30

Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.
Beneficial auditory and cognitive effects of auditory brainstem implantation in children.

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Colletti, Liliana

2007-09-01

This preliminary study demonstrates the development of hearing ability and shows that there is a significant improvement in some cognitive parameters related to selective visual/spatial attention and to fluid or multisensory reasoning, in children fitted with auditory brainstem implantation (ABI). The improvement in cognitive paramenters is due to several factors, among which there is certainly, as demonstrated in the literature on a cochlear implants (CIs), the activation of the auditory sensory canal, which was previously absent. The findings of the present study indicate that children with cochlear or cochlear nerve abnormalities with associated cognitive deficits should not be excluded from ABI implantation. The indications for ABI have been extended over the last 10 years to adults with non-tumoral (NT) cochlear or cochlear nerve abnormalities that cannot benefit from CI. We demonstrated that the ABI with surface electrodes may provide sufficient stimulation of the central auditory system in adults for open set speech recognition. These favourable results motivated us to extend ABI indications to children with profound hearing loss who were not candidates for a CI. This study investigated the performances of young deaf children undergoing ABI, in terms of their auditory perceptual development and their non-verbal cognitive abilities. In our department from 2000 to 2006, 24 children aged 14 months to 16 years received an ABI for different tumour and non-tumour diseases. Two children had NF2 tumours. Eighteen children had bilateral cochlear nerve aplasia. In this group, nine children had associated cochlear malformations, two had unilateral facial nerve agenesia and two had combined microtia, aural atresia and middle ear malformations. Four of these children had previously been fitted elsewhere with a CI with no auditory results. One child had bilateral incomplete cochlear partition (type II); one child, who had previously been fitted unsuccessfully elsewhere
Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion.

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Lee, A Moses; Hoy, Jennifer L; Bonci, Antonello; Wilbrecht, Linda; Stryker, Michael P; Niell, Cristopher M

2014-07-16

Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion. Copyright © 2014 Elsevier Inc. All rights reserved.

Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants

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Joubert, Fanny; Loiseau, Camille; Perrin-Terrin, Anne-Sophie; Cayetanot, Florence; Frugière, Alain; Voituron, Nicolas; Bodineau, Laurence

2016-01-01

We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral, and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas ~45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labeled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labeled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labeled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by (i) the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, (ii) the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and (iii) the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modeling the breathing network of premature infants. PMID:28018238
Key brainstem structures activated during hypoxic exposure in one-day-old mice highlight characteristics for modelling breathing network in premature infants

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Fanny JOUBERT

2016-12-01

Full Text Available We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas approximately 45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labelled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labelled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labelled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by i the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, ii the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and iii the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modelling the breathing network of premature infants.
Auditory brainstem responses of CBA/J mice with neonatal conductive hearing losses and treatment with GM1 ganglioside.

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Money, M K; Pippin, G W; Weaver, K E; Kirsch, J P; Webster, D B

1995-07-01

Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal conductive hearing loss ameliorates the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The present investigation demonstrates the extent of a conductive loss caused by atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate the conductive hearing loss. Auditory brainstem responses were recorded from four groups of seven mice each: two groups received daily subcutaneous injections of saline (one group had normal hearing; the other had a conductive hearing loss); the other two groups received daily subcutaneous injections of GM1 ganglioside (one group had normal hearing; the other had a conductive hearing loss). In mice with a conductive loss, decreases in hearing sensitivity were greatest at high frequencies. The decreases were determined by comparing mean ABR thresholds of the conductive loss mice with those of normal hearing mice. The conductive hearing loss induced in the mice in this study was similar to that seen in humans with congenital aural atresias. GM1 ganglioside treatment had no significant effect on ABR wave I thresholds or latencies in either group.
The auditory brainstem response in two lizard species.

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Brittan-Powell, Elizabeth F; Christensen-Dalsgaard, Jakob; Tang, Yezhong; Carr, Catherine; Dooling, Robert J

2010-08-01

Although lizards have highly sensitive ears, it is difficult to condition them to sound, making standard psychophysical assays of hearing sensitivity impractical. This paper describes non-invasive measurements of the auditory brainstem response (ABR) in both Tokay geckos (Gekko gecko; nocturnal animals, known for their loud vocalizations) and the green anole (Anolis carolinensis, diurnal, non-vocal animals). Hearing sensitivity was measured in 5 geckos and 7 anoles. The lizards were sedated with isoflurane, and ABRs were measured at levels of 1 and 3% isoflurane. The typical ABR waveform in response to click stimulation showed one prominent and several smaller peaks occurring within 10 ms of the stimulus onset. ABRs to brief tone bursts revealed that geckos and anoles were most sensitive between 1.6-2 kHz and had similar hearing sensitivity up to about 5 kHz (thresholds typically 20-50 dB SPL). Above 5 kHz, however, anoles were more than 20 dB more sensitive than geckos and showed a wider range of sensitivity (1-7 kHz). Generally, thresholds from ABR audiograms were comparable to those of small birds. Best hearing sensitivity, however, extended over a larger frequency range in lizards than in most bird species.
Effects of 12 months continuous positive airway pressure on sympathetic activity related brainstem function and structure in obstructive sleep apnea.

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Luke Anthony Henderson

2016-03-01

Full Text Available Muscle sympathetic nerve activity (MSNA is greatly elevated in patients with obstructive sleep apnoea (OSA during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 subjects with OSA prior to and following 6 and 12 months of continuous positive airway pressure (CPAP treatment. We found that 6 and 12 months of CPAP treatment significantly reduced the elevated resting MSNA in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MNSA likely due to its effects on restoring brainstem structure and function.
Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats

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Tsujimura, Takanori; Kondo, Masahiro; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Saito, Kimiko; Tohara, Haruka; Ueda, Koichiro; Sessle, Barry J; Iwata, Koichi

2009-01-01

In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and γ-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABAA receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABAA receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin–NTS, lingual muscle–NTS and lingual muscle–Pa5–NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures. PMID:19124539
Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats.

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Tsujimura, Takanori; Kondo, Masahiro; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Saito, Kimiko; Tohara, Haruka; Ueda, Koichiro; Sessle, Barry J; Iwata, Koichi

2009-02-15

In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and gamma-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABA(A) receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABA(A) receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin-NTS, lingual muscle-NTS and lingual muscle-Pa5-NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures.
Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area—an anterograde tract-tracing study

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Papp, Rege S.; Palkovits, Miklós

2014-01-01

The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribu...
Immunohistochemical characterisation and localisation of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and the effects of unilateral vestibular deafferentation.

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Ashton, John C; Zheng, Yiwen; Liu, Ping; Darlington, Cynthia L; Smith, Paul F

2004-09-24

CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular pathways. We used immunohistochemistry to study the distribution of CB1 receptor protein in the VNC, and Western blotting to measure CB1 receptor expression in the VNC following unilateral vestibular deafferentation (UVD); the hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were also analysed for comparison. This study confirms a previous electrophysiological demonstration that CB1 receptors exist in significant densities in the VNC and are likely to contribute to the neurochemical control of the vestibular reflexes. Nonetheless, CB1 receptor expression did not change significantly in the VNC during vestibular compensation. In addition, despite some small but significant changes in CB1 receptor expression in the CA2/3 and the DG following UVD, in no case were these differences statistically significant in comparison to both control groups.
Stress-induced changes in the expression of the clock protein PERIOD1 in the rat limbic forebrain and hypothalamus: role of stress type, time of day, and predictability.

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Sherin Al-Safadi

Full Text Available Stressful events can disrupt circadian rhythms in mammals but mechanisms underlying this disruption remain largely unknown. One hypothesis is that stress alters circadian protein expression in the forebrain, leading to functional dysregulation of the brain circadian network and consequent disruption of circadian physiological and behavioral rhythms. Here we characterized the effects of several different stressors on the expression of the core clock protein, PER1 and the activity marker, FOS in select forebrain and hypothalamic nuclei in rats. We found that acute exposure to processive stressors, restraint and forced swim, elevated PER1 and FOS expression in the paraventricular and dorsomedial hypothalamic nuclei and piriform cortex but suppressed PER1 and FOS levels exclusively in the central nucleus of the amygdala (CEAl and oval nucleus of the bed nucleus of the stria terminalis (BNSTov. Conversely, systemic stressors, interleukin-1β and 2-Deoxy-D-glucose, increased PER1 and FOS levels in all regions studied, including the CEAl and BNSTov. PER1 levels in the suprachiasmatic nucleus (SCN, the master pacemaker, were unaffected by any of the stress manipulations. The effect of stress on PER1 and FOS was modulated by time of day and, in the case of daily restraint, by predictability. These results demonstrate that the expression of PER1 in the forebrain is modulated by stress, consistent with the hypothesis that PER1 serves as a link between stress and the brain circadian network. Furthermore, the results show that the mechanisms that control PER1 and FOS expression in CEAl and BNSTov are uniquely sensitive to differences in the type of stressor. Finally, the finding that the effect of stress on PER1 parallels its effect on FOS supports the idea that Per1 functions as an immediate-early gene. Our observations point to a novel role for PER1 as a key player in the interface between stress and circadian rhythms.
Test-retest reliability of speech-evoked auditory brainstem response in healthy children at a low sensation level.

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Zakaria, Mohd Normani; Jalaei, Bahram

2017-11-01

Auditory brainstem responses evoked by complex stimuli such as speech syllables have been studied in normal subjects and subjects with compromised auditory functions. The stability of speech-evoked auditory brainstem response (speech-ABR) when tested over time has been reported but the literature is limited. The present study was carried out to determine the test-retest reliability of speech-ABR in healthy children at a low sensation level. Seventeen healthy children (6 boys, 11 girls) aged from 5 to 9 years (mean = 6.8 ± 3.3 years) were tested in two sessions separated by a 3-month period. The stimulus used was a 40-ms syllable /da/ presented at 30 dB sensation level. As revealed by pair t-test and intra-class correlation (ICC) analyses, peak latencies, peak amplitudes and composite onset measures of speech-ABR were found to be highly replicable. Compared to other parameters, higher ICC values were noted for peak latencies of speech-ABR. The present study was the first to report the test-retest reliability of speech-ABR recorded at low stimulation levels in healthy children. Due to its good stability, it can be used as an objective indicator for assessing the effectiveness of auditory rehabilitation in hearing-impaired children in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.
Brainstem auditory evoked response characteristics in normal-hearing subjects with chronic tinnitus and in non-tinnitus group

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Shadman Nemati

2014-06-01

Full Text Available Background and Aim: While most of the people with tinnitus have some degrees of hearing impairment, a small percent of patients admitted to ear, nose and throat clinics or hearing evaluation centers are those who complain of tinnitus despite having normal hearing thresholds. This study was performed to better understanding of the reasons of probable causes of tinnitus and to investigate possible changes in the auditory brainstem function in normal-hearing patients with chronic tinnitus.Methods: In this comparative cross-sectional, descriptive and analytic study, 52 ears (26 with and 26 without tinnitus were examined. Components of the auditory brainstem response (ABR including wave latencies and wave amplitudes were determined in the two groups and analyzed using appropriate statistical methods.Results: The mean differences between the absolute latencies of waves I, III and V was less than 0.1 ms between the two groups that was not statistically significant. Also, the interpeak latency values of waves I-III, III-V and I-V in both groups had no significant difference. Only, the V/I amplitude ratio in the tinnitus group was significantly higher (p=0.04.Conclusion: The changes observed in amplitude of waves, especially in the latter ones, can be considered as an indication of plastic changes in neuronal activity and its possible role in generation of tinnitus in normal-hearing patients.
A rare case of acute poster ior reversible encephalopathy syndrome involving brainstem in a child

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Olfa Chakroun-Walha

2016-11-01

Full Text Available Posterior reversible encephalopathy syndrome (PRES is a rare entity involving brainstem in very rare reported cases. We describe here the case of a boy who presented to the emergency department for headaches and strabismus. Diagnosis of PRES was retained by magnetic resonance imaging. The causes were blood pressure urgency and renal failure. Location of lesions was very rarely reported in literature and neurological troubles were persistent. Emergency physicians should evocate PRES each time there is a clinical context associated with neurological troubles by a normal brain CT scan. Early diagnosis is very important to treat its causes and improve prognosis.
Brainstem Auditory Evoked Potentials in Patients with Subarachnoid Haemorrhage

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Mikhail Matveev

2009-10-01

Full Text Available Objective. The aim of the present study is to typify BAEPs configurations of patients with different location of lesions caused by subarachnoid haemorrhage (SAH and the ensuing complications, in view of assessing the auditory-brainstem system disturbance.Methods. The typization was performed by comparing BAEPs with standard patterns from two sets of types of BAEPs by ipsilateral and binaural stimulation and by cross-stimulation.Results. 94 BAEPs were used for collection of normal referential values: for the absolute latencies and the absolute amplitudes of waves I, II, III, IV and V; for inter-peak latencies I-III, II-III, III-V, I-V and II-V; for amplitude ratios I/V and III/V. 146 BAEPs of patients with mild SAH and 55 from patients with severe SAH, were typified. In 5 types of BAEPs out of a total of 11, the percentage of the potentials in patients with mild SAH and severe SAH differed significantly (p<0.01.Conclusions. The use of sets of types of BAEPs by ipsilateral, binaural and cross-stimulation correctly classifies the potentials in patients with mild and severe SAH.
The maturational process of the auditory system in the first year of life characterized by brainstem auditory evoked potentials

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Raquel Beltrão Amorim

2009-01-01

Full Text Available The study of brainstem auditory evoked potentials (BAEP allows obtaining the electrophysiological activity generated in the cochlear nerve to the inferior colliculus. In the first months of life, a period of greater neuronal plasticity, important changes are observed in the absolute latency and inter-peak intervals of BAEP, which occur up to the completion of the maturational process, around 18 months of life in full-term newborns, when the response is similar to that of adults. OBJECTIVE: The goal of this study was to establish normal values of absolute latencies for waves I, III and V and inter-peak intervals I-III, III-V and I-V of the BAEP performed in full-term infants attending the Infant Hearing Health Program of the Speech-Language Pathology and Audiology Course at Bauru School of Dentistry, Brazil, with no risk history for hearing impairment. MATERIAL AND METHODS: The stimulation parameters were: rarefaction click stimulus presented by the 3ª insertion phone, intensity of 80 dBnHL and a rate of 21.1 c/s, band-pass filter of 30 and 3,000 Hz and average of 2,000 stimuli. A sample of 86 infants was first divided according to their gestational age in preterm (n=12 and full-term (n=74, and then according to their chronological age in three periods: P1: 0 to 29 days (n=46, P2: 30 days to 5 months 29 days (n=28 and P3: above 6 months (n= 12. RESULTS: The absolute latency of wave I was similar to that of adults, generally in the 1st month of life, demonstrating a complete process maturity of the auditory nerve. For waves III and V, there was a gradual decrease of absolute latencies with age, characterizing the maturation of axons and synaptic mechanisms in the brainstem level. CONCLUSION: Age proved to be a determining factor in the absolute latency of the BAEP components, especially those generated in the brainstem, in the first year of life.
Early developmental gene enhancers affect subcortical volumes in the adult human brain.

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Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

2016-05-01

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Distribution and morphology of serotonin-immunoreactive neurons in the brainstem of the New Zealand white rabbit

DEFF Research Database (Denmark)

Bjarkam, C R; Sørensen, J C; Geneser, F A

1997-01-01

The aim of the present study was to demonstrate the morphology and distribution of the serotonergic neurons in the brainstem of the New Zealand white rabbit by using a highly specific immunocytochemical procedure. It was possible to divide the serotonergic neurons into a rostral group, which......, which were large and multipolar, were morphologically different from the serotonergic neurons in the midline, which were mostly small and relatively nonpolar. The serotonergic system of the New Zealand white rabbit has undergone a major lateralization, like the serotonergic system of man and higher...
[Neuronal control of posture and locomotion in decerebrated and spinalized animals].

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Musienko, P E; Gorskiĭ, O V; Kilimnik, V A; Kozlovskaia, I B; Courtine, G; Edgerton, V R; Gerasimenko, Iu P

2013-03-01

We have found that the brainstem-spinal cord circuitry of decerebrated cats actively maintain the equilibrium during standing, walking and imposed mechanical perturbations similar to that observed in intact animals. The corrective hindlimb motor responses during standing included redistribution of the extensor activity ipsilateral and contralateral to perturbation. The postural corrections in walking cats were due to considerable modification of EMG pattern in the limbs as well as changing of the swing-stance phases of the step cycle and ground reaction forces depending of perturbation side. Thus the basic mechanisms for balance control of decerebrated animals in these two forms of motor behavior are different. Balance-related adjustments relied entirely on the integration of somatosensory information arising from the moving hindquarters because of the suppression of vestibular, visual, and head-neck-trunk sensory input. We propose that the somatosensory input from the hindquarters in concert with the lumbosacral spinal circuitry can control the dynamics of the hindquarters sufficient to sustain balance. We found that, after isolation from the brainstem or forebrain, lumbosacral circuits receiving tonic epidural electrical stimulation can effectively control equilibrium during standing and stepping. Detailed analyses of the relationships among muscle activity, trunk kinematics, and limb kinetics indicate that spinal motor systems utilize a combination of feedback and feedforward strategies to maintain dynamic equilibrium during walking. The unexpected ability of spinal circuitries to exert efficient postural control in the presence of epidural electrical stimulation in decerebrated and spinal cats have significant implications for the potential of humans with a severe spinal cord injury to regain a significant level of functional standing and walking capacities.
Stacking denoising auto-encoders in a deep network to segment the brainstem on MRI in brain cancer patients: A clinical study.

Science.gov (United States)

Dolz, Jose; Betrouni, Nacim; Quidet, Mathilde; Kharroubi, Dris; Leroy, Henri A; Reyns, Nicolas; Massoptier, Laurent; Vermandel, Maximilien

2016-09-01

Delineation of organs at risk (OARs) is a crucial step in surgical and treatment planning in brain cancer, where precise OARs volume delineation is required. However, this task is still often manually performed, which is time-consuming and prone to observer variability. To tackle these issues a deep learning approach based on stacking denoising auto-encoders has been proposed to segment the brainstem on magnetic resonance images in brain cancer context. Additionally to classical features used in machine learning to segment brain structures, two new features are suggested. Four experts participated in this study by segmenting the brainstem on 9 patients who underwent radiosurgery. Analysis of variance on shape and volume similarity metrics indicated that there were significant differences (p<0.05) between the groups of manual annotations and automatic segmentations. Experimental evaluation also showed an overlapping higher than 90% with respect to the ground truth. These results are comparable, and often higher, to those of the state of the art segmentation methods but with a considerably reduction of the segmentation time. Copyright © 2016 Elsevier Ltd. All rights reserved.
Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

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Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

2017-12-04

Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

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Lauritzen, Knut H; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A; Storm-Mathisen, Jon; Bergersen, Linda H

2016-12-01

Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABA A ) receptor subunits α 1 . However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders. Copyright © 2016 Elsevier Inc. All rights reserved.
The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrain

DEFF Research Database (Denmark)

Leone, Dino P; Srinivasan, Karpagam; Brakebusch, Cord

2010-01-01

family member, Cdc42, affects the polarity and proliferation of radial glial cells in the VZ. Here, we show that another family member, Rac1, is required for the normal proliferation and differentiation of SVZ progenitors and for survival of both VZ and SVZ progenitors. A forebrain-specific loss of Rac1...... leads to an SVZ-specific reduction in proliferation, a concomitant increase in cell cycle exit, and premature differentiation. In Rac1 mutants, the SVZ and VZ can no longer be delineated, but rather fuse to become a single compact zone of intermingled cells. Cyclin D2 expression, which is normally...... expressed by both VZ and SVZ progenitors, is reduced in Rac1 mutants, suggesting that the mutant cells differentiate precociously. Rac1-deficient mice can still generate SVZ-derived upper layer neurons, indicating that Rac1 is not required for the acquisition of upper layer neuronal fates, but instead...
Rapid measurement of auditory filter shape in mice using the auditory brainstem response and notched noise.

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Lina, Ioan A; Lauer, Amanda M

2013-04-01

The notched noise method is an effective procedure for measuring frequency resolution and auditory filter shapes in both human and animal models of hearing. Briefly, auditory filter shape and bandwidth estimates are derived from masked thresholds for tones presented in noise containing widening spectral notches. As the spectral notch widens, increasingly less of the noise falls within the auditory filter and the tone becomes more detectible until the notch width exceeds the filter bandwidth. Behavioral procedures have been used for the derivation of notched noise auditory filter shapes in mice; however, the time and effort needed to train and test animals on these tasks renders a constraint on the widespread application of this testing method. As an alternative procedure, we combined relatively non-invasive auditory brainstem response (ABR) measurements and the notched noise method to estimate auditory filters in normal-hearing mice at center frequencies of 8, 11.2, and 16 kHz. A complete set of simultaneous masked thresholds for a particular tone frequency were obtained in about an hour. ABR-derived filter bandwidths broadened with increasing frequency, consistent with previous studies. The ABR notched noise procedure provides a fast alternative to estimating frequency selectivity in mice that is well-suited to high through-put or time-sensitive screening. Copyright © 2013 Elsevier B.V. All rights reserved.
SU-F-T-392: Superior Brainstem and Cochlea Sparing with VMAT for Glioblastoma Multiforme

Energy Technology Data Exchange (ETDEWEB)

Briere, TM; McAleer, MF; Levy, LB; Yang, JN; Anderson, MD [Cancer Ctr., Houston, TX (United States)

2016-06-15

Purpose: Volumetric arc therapy (VMAT) can provide similar target coverage and normal tissue sparing as IMRT but with shorter treatment times. At our institution VMAT was adopted for the treatment glioblastoma multiforme (GBM) after a small number of test plans demonstrated its non-inferiority. In this study, we compare actual clinical treatment plans for a larger cohort of patients treated with either VMAT or IMRT. Methods: 90 GBM patients were included in this study, 45 treated with IMRT and 45 with VMAT. All planning target volumes (PTVs) were prescribed a dose of 50 Gy, with a simultaneous integrated boost to 60 Gy. Most IMRT plans used 5 non-coplanar beams, while most VMAT plans used 2 coplanar beams. Statistical analysis was performed using Fisher’s exact test or the Wilcoxon-Mann-Whitney rank sum test. Included in the analysis were patient and treatment characteristics as well as the doses to the target volumes and organs at risk. Results: Treatment times for the VMAT plans were reduced by 5 minutes compared with IMRT. The PTV coverage was similar, with at least 95% covered for all plans, while the median boost PTV dose differed by 0.1 Gy between the IMRT and VMAT cohorts. The doses to the brain, optic chiasm, optic nerves and eyes were not significantly different. The mean dose to the brainstem, however, was 9.4 Gy less with VMAT (p<0.001). The dose to the ipsilateral and contralateral cochleae were respectively 19.7 and 9.5 Gy less (p<0.001). Conclusion: Comparison of clinical treatment plans for separate IMRT and VMAT cohorts demonstrates that VMAT can save substantial treatment time while providing similar target coverage and superior sparing of the brainstem and cochleae. To our knowledge this is the first study to demonstrate this benefit of VMAT in the management of GBM.
Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

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Eduardo Bondan

Full Text Available ABSTRACT Recent studies have demonstrated that curcumin (Cur has antioxidant, anti-inflammatory and anti-fibrotic effects. Ethidium bromide (EB injections into the central nervous system (CNS are known to induce local oligodendroglial and astrocytic loss, resulting in primary demyelination and neuroinflammation. Peripheral astrogliosis is seen around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP. This investigation aimed to evaluate the effect of Cur administration on astrocytic response following gliotoxic injury. Wistar rats were injected with EB into the cisterna pontis and treated, or not, with Cur (100 mg/kg/day, intraperitoneal route during the experimental period. Brainstem sections were collected at 15, 21 and 31 days after EB injection and processed for GFAP immunohistochemical staining. Astrocytic reactivity was measured in a computerized system for image analysis. In Cur-treated rats, the GFAP-stained area around the lesion was significantly smaller in all periods after EB injection compared to untreated animals, showing that Cur reduces glial scar development following injury.
Proposed Toxic and Hypoxic Impairment of a Brainstem Locus in Autism

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Woody R. McGinnis

2013-12-01

Full Text Available Electrophysiological findings implicate site-specific impairment of the nucleus tractus solitarius (NTS in autism. This invites hypothetical consideration of a large role for this small brainstem structure as the basis for seemingly disjointed behavioral and somatic features of autism. The NTS is the brain’s point of entry for visceral afference, its relay for vagal reflexes, and its integration center for autonomic control of circulatory, immunological, gastrointestinal, and laryngeal function. The NTS facilitates normal cerebrovascular perfusion, and is the seminal point for an ascending noradrenergic system that modulates many complex behaviors. Microvascular configuration predisposes the NTS to focal hypoxia. A subregion—the “pNTS”—permits exposure to all blood-borne neurotoxins, including those that do not readily transit the blood-brain barrier. Impairment of acetylcholinesterase (mercury and cadmium cations, nitrates/nitrites, organophosphates, monosodium glutamate, competition for hemoglobin (carbon monoxide, nitrates/nitrites, and higher blood viscosity (net systemic oxidative stress are suggested to potentiate microcirculatory insufficiency of the NTS, and thus autism.
Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area – an anterograde tract-tracing study

OpenAIRE

Rege Sugárka Papp; Rege Sugárka Papp; Miklos ePalkovits; Miklos ePalkovits

2014-01-01

The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribu...
Calretinin as a marker for premotor neurons involved in upgaze in human brainstem

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Christopher eAdamczyk

2015-12-01

Full Text Available Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF, which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of calretinin input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and calretinin may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and calretinin positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan component of perineuronal nets, parvalbumin or calretinin and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without calretinin coexpression, which were intermingled. The parvalbumin/calretinin positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking calretinin are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as
Brain Activity and Human Unilateral Chewing

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Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

2012-01-01

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631
Influence of sucrose ingestion on brainstem and hypothalamic intrinsic oscillations in lean and obese women.

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Kilpatrick, Lisa A; Coveleskie, Kristen; Connolly, Lynn; Labus, Jennifer S; Ebrat, Bahar; Stains, Jean; Jiang, Zhiguo; Suyenobu, Brandall Y; Raybould, Helen E; Tillisch, Kirsten; Mayer, Emeran A

2014-05-01

The study of intrinsic fluctuations in the blood oxygen level-dependent signal of functional magnetic resonance imaging can provide insight into the effect of physiologic states on brain processes. In an effort to better understand the brain-gut communication induced by the absorption and metabolism of nutrients in healthy lean and obese individuals, we investigated whether ingestion of nutritive and non-nutritive sweetened beverages differentially engages the hypothalamus and brainstem vagal pathways in lean and obese women. In a 2-day, double-blind crossover study, 11 lean and 11 obese healthy women underwent functional magnetic resonance imaging scans after ingestion of 2 beverages of different sucrose content, but identical sweetness. During scans, subjects rested with eyes closed. Blood oxygen level-dependent fluctuations demonstrated significantly greater power in the highest frequency band (slow-3: 0.073-0.198 Hz) after ingestion of high-sucrose compared with low-sucrose beverages in the nucleus tractus solitarius for both groups. Obese women had greater connectivity between the right lateral hypothalamus and a reward-related brain region and weaker connectivity with homeostasis and gustatory-related brain regions than lean women. In a functional magnetic resonance imaging study, we observed sucrose-related changes in oscillatory dynamics of blood oxygen level-dependent fluctuations in brainstem and hypothalamus in lean and obese women. The observed frequency changes are consistent with a rapid vagally mediated mechanism due to nutrient absorption, rather than sweet taste receptor activation. These findings provide support for altered interaction between homeostatic and reward networks in obese individuals. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
Diffusion tractography of the subcortical auditory system in a postmortem human brain

OpenAIRE

Sitek, Kevin

2017-01-01

The subcortical auditory system is challenging to identify with standard human brain imaging techniques: MRI signal decreases toward the center of the brain as well as at higher resolution, both of which are necessary for imaging small brainstem auditory structures.Using high-resolution diffusion-weighted MRI, we asked:Can we identify auditory structures and connections in high-resolution ex vivo images?Which structures and connections can be mapped in vivo?
Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.

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Mennenga, Sarah E; Gerson, Julia E; Koebele, Stephanie V; Kingston, Melissa L; Tsang, Candy W S; Engler-Chiurazzi, Elizabeth B; Baxter, Leslie C; Bimonte-Nelson, Heather A

2015-04-01

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory
Enhanced auditory brainstem response and parental bonding style in children with gastrointestinal symptoms.

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Shizuka Seino

Full Text Available The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS are unclear. We hypothesized that children with chronic gastrointestinal (GI symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP responses and receive more inadequate parental bonding.Children aged seven and their mothers (141 pairs participated. BAEP was measured by summation of 1,000 waves of the electroencephalogram triggered by 75 dB click sounds. The mothers completed their Children's Somatization Inventory (CSI and Parental Bonding Instrument (PBI. CSI results revealed 66 (42% children without GI symptoms (controls and 75 (58% children with one or more GI symptoms (GI group. The III wave in the GI group (median 4.10 interquartile range [3.95-4.24] ms right, 4.04 [3.90-4.18] ms left had a significantly shorter peak latency than controls (4.18 [4.06-4.34] ms right, p = 0.032, 4.13 [4.02-4.24] ms left, p = 0.018. The female GI group showed a significantly shorter peak latency of the III wave (4.00 [3.90-4.18] ms than controls (4.18 [3.97-4.31] ms, p = 0.034 in the right side. BAEP in the male GI group did not significantly differ from that in controls. GI scores showed a significant correlation with the peak latency of the III wave in the left side (rho = -0.192, p = 0.025. The maternal care PBI scores in the GI group (29 [26]-[33] were significantly lower than controls (31 [28.5-33], p = 0.010, while the maternal over-protection PBI scores were significantly higher in the GI group (16 [12]-[17] than controls (13 [10.5-16], p = 0.024. Multiple regression analysis in females also supported these findings.It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms.
Organization of the auditory brainstem in a lizard, Gekko gecko. I. Auditory nerve, cochlear nuclei, and superior olivary nuclei.

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Tang, Yezhong; Christensen-Dalsgaard, Jakob; Carr, Catherine E

2012-06-01

We used tract tracing to reveal the connections of the auditory brainstem in the Tokay gecko (Gekko gecko). The auditory nerve has two divisions, a rostroventrally directed projection of mid- to high best-frequency fibers to the nucleus angularis (NA) and a more dorsal and caudal projection of low to middle best-frequency fibers that bifurcate to project to both the NA and the nucleus magnocellularis (NM). The projection to NM formed large somatic terminals and bouton terminals. NM projected bilaterally to the second-order nucleus laminaris (NL), such that the ipsilateral projection innervated the dorsal NL neuropil, whereas the contralateral projection crossed the midline and innervated the ventral dendrites of NL neurons. Neurons in NL were generally bitufted, with dorsoventrally oriented dendrites. NL projected to the contralateral torus semicircularis and to the contralateral ventral superior olive (SOv). NA projected to ipsilateral dorsal superior olive (SOd), sent a major projection to the contralateral SOv, and projected to torus semicircularis. The SOd projected to the contralateral SOv, which projected back to the ipsilateral NM, NL, and NA. These results suggest homologous patterns of auditory connections in lizards and archosaurs but also different processing of low- and high-frequency information in the brainstem. Copyright © 2011 Wiley Periodicals, Inc.
Brainstem dysfunction in patients with late-onset Lennox-Gastaut syndrome: Voxel-based morphometry and tract-based spatial statistics study

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Kang Min Park

2016-01-01

Full Text Available Background: There have been a few reports of patients who developed Lennox-Gastaut syndrome (LGS in the second decades of their life. Objectives: The aim of this study was to investigate electroclinical presentation in patients with late-onset LGS. In addition, we evaluated structural abnormalities of the brain, which may give some clue about the common pathogenic pathway in LGS. Materials and Methods: We enrolled the patients with late-onset LGS. We collected electroclinical characteristics of the patients and evaluated structural abnormalities using voxel-based morphometry (VBM and tract-based spatial statistics (TBSS analysis. Results: The three subjects were diagnosed with late-onset LGS. The patients have no mental retardation and normal background activities on electroencephalography (EEG, and they had generalized paroxysmal fast activities on EEG, especially during sleep. The TBSS analysis revealed that fractional anisotropy values in the patients were significantly reduced in the white matter of brainstem compared with normal controls. However, VBM analysis did not show any significant difference between the patients and normal controls. Conclusions: Patients with late-onset LGS have different clinical and EEG characteristics from those with early-onset LGS. In addition, we demonstrated that brainstem dysfunction might contribute to the pathogenesis of late-onset LGS.
Piracetam-induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.

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Durand-Rivera, A; Gonzalez-Pina, R; Hernandez-Godinez, B; Ibanez-Contreras, A; Bueno-Nava, A; Alfaro-Rodriguez, A

2012-10-01

We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. In this report, we discuss the significance of these observations. © 2012 John Wiley & Sons A/S.
Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons

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Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David

2014-01-01

Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676
Topological characteristics of brainstem lesions in clinically definite and clinically probable cases of multiple sclerosis: An MRI-study

International Nuclear Information System (INIS)

Brainin, M.; Omasits, M.; Reisner, T.; Neuhold, A.; Wicke, L.

1987-01-01

Disseminated lesions in the white matter of the cerebral hemispheres and confluent lesions at the borders of the lateral ventricles as seen on MRI are both considered acceptable paraclinical evidence for the diagnosis of multiple sclerosis. Similar changes are, however, also found in vascular diseases of the brain. We therefore aimed at identifying those additional traits in the infratentorial region, which in our experience are not frequently found in cerebrovascular pathology. We evaluated MR brain scans of 68 patients and found pontine lesions in 71% of cases with a clinically definite diagnosis (17 out of 24) and in 33% of cases with a probable diagnosis (14 out of 43). Lesions in the medulla oblongata were present in 50% and 16%, respectively, and in the midbrain in 25% and 7%, respectively. With rare exceptions all brainstem lesions were contiguous with the cisternal or ventricular cerebrospinal fluid spaces. In keeping with post-mortem reports the morphological spectrum ranged from large confluent patches to solitary, well delineated paramedian lesions or discrete linings of the cerebrospinal fluid border zones and were most clearly depicted from horizontal and sagittal T2 weighted SE-sequences. If there is a predilection for the outer or inner surfaces of the brainstem, such lesions can be considered an additional typical feature of multiple sclerosis and can be more reliably weighted as paraclinical evidence for a definite diagnosis. (orig.)
Clinical Value of Dorsal Medulla Oblongata Involvement Detected with Conventional MRI for Prediction of Outcome in Children with Enterovirus 71-related Brainstem Encephalitis.

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Liu, Kun; Zhou, Yongjin; Cui, Shihan; Song, Jiawen; Ye, Peipei; Xiang, Wei; Huang, Xiaoyan; Chen, Yiping; Yan, Zhihan; Ye, Xinjian

2018-04-05

Brainstem encephalitis is the most common neurologic complication after enterovirus 71 infection. The involvement of brainstem, especially the dorsal medulla oblongata, can cause severe sequelae or death in children with enterovirus 71 infection. We aimed to determine the prevalence of dorsal medulla oblongata involvement in children with enterovirus 71-related brainstem encephalitis (EBE) by using conventional MRI and to evaluate the value of dorsal medulla oblongata involvement in outcome prediction. 46 children with EBE were enrolled in the study. All subjects underwent a 1.5 Tesla MR examination of the brain. The disease distribution and clinical data were collected. Dichotomized outcomes (good versus poor) at longer than 6 months were available for 28 patients. Logistic regression was used to determine whether the MRI-confirmed dorsal medulla oblongata involvement resulted in improved clinical outcome prediction when compared with other location involvement. Of the 46 patients, 35 had MRI evidence of dorsal medulla oblongata involvement, 32 had pons involvement, 10 had midbrain involvement, and 7 had dentate nuclei involvement. Patients with dorsal medulla oblongata involvement or multiple area involvement were significantly more often in the poor outcome group than in the good outcome group. Logistic regression analysis showed that dorsal medulla oblongata involvement was the most significant single variable in outcome prediction (predictive accuracy, 90.5%), followed by multiple area involvement, age, and initial glasgow coma scale score. Dorsal medulla oblongata involvement on conventional MRI correlated significantly with poor outcomes in EBE children, improved outcome prediction when compared with other clinical and disease location variables, and was most predictive when combined with multiple area involvement, glasgow coma scale score and age.
Detection of Perinatal Cytomegalovirus Infection and Sensorineural Hearing Loss in Belgian Infants by Measurement of Automated Auditory Brainstem Response▿

OpenAIRE

Verbeeck, Jannick; Van Kerschaver, Erwin; Wollants, Elke; Beuselinck, Kurt; Stappaerts, Luc; Van Ranst, Marc

2008-01-01

Since auditory disability causes serious problems in the development of speech and in the total development of a child, it is crucial to diagnose possible hearing impairment as soon as possible after birth. This study evaluates the neonatal hearing screening program in Flanders, Belgium. The auditory ability of 118,438 babies was tested using the automated auditory brainstem response. We selected 194 babies with indicative hearing impairment and 332 matched controls to investigate the associa...

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