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Sample records for auditory brain stem

  1. Auditory brain-stem responses in adrenomyeloneuropathy.

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    Grimes, A M; Elks, M L; Grunberger, G; Pikus, A M

    1983-09-01

    We studied three patients with adrenomyeloneuropathy. Complete audiologic assessment was obtained: two patients showed unimpaired peripheral hearing and one showed a mild high-frequency hearing loss. Auditory brain-stem responses were abnormal in both ears of all subjects, with one subject showing no response above wave I, and the other two having significant wave I to III and wave III to V interval prolongations. We concluded that auditory brain-stem response testing provides a simple, valid, reliable method for demonstrating neurologic abnormality in adrenomyeloneuropathy even prior to evidence of clinical signs.

  2. [State dependent modification of auditory brain stem potentials].

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    Maier, R; Rebentisch, E

    1984-11-01

    It is well known, amplitudes and latencies of auditory brain stem potentials are almost independent of viligance state. Contrary to that, simple cognitive requirements effect amplitude changes (enhancement of variance, amplitude reduction) in a part 2/3) of the subjects.

  3. Auditory Brain Stem Processing in Reptiles and Amphibians: Roles of Coupled Ears

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    Willis, Katie L.; Christensen-Dalsgaard, Jakob; Carr, Catherine

    2014-01-01

    Comparative approaches to the auditory system have yielded great insight into the evolution of sound localization circuits, particularly within the nonmammalian tetrapods. The fossil record demonstrates multiple appearances of tympanic hearing, and examination of the auditory brain stem of variou...

  4. Age and Gender Effects On Auditory Brain Stem Response (ABR

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    Yones Lotfi

    2012-10-01

    Full Text Available Objectives: Auditory Brain Stem Response (ABR is a result of eight nerve and brain stem nuclei stimulation. Several factors may affect the latencies, interpeak latencies and amplitudes in ABR especially sex and age. In this study, age and sex influence on ABR were studied. Methods: This study was performed on 120 cases (60 males and 60 females at Akhavan rehabilitation center of university of welfare and rehabilitation sciences, Tehran, Iran. Cases were divided in three age groups: 18-30, 31-50 and 51-70 years old. Each age group consists of 20 males and 20 females. Age and sex influences on absolute latency of wave I and V, and IPL of I-V were examined. Results: Independent t test showed that females have significantly shorter latency of wave I, V, and IPL I-V latency (P<0.001 than males. Two way ANOVA showed that latency of wave I, V and IPL I-V in 51-70 years old group was significantly higher than 18-30 and 31-50 years old groups (P<0.001 Discussion: According to the results of present study and similar studies, in clinical practice, different norms for older adults and both genders should be established.

  5. Brain stem auditory evoked responses in human infants and adults

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    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  6. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

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    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y. (Queen Mary Hospital, Hong Kong (Hong Kong))

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  7. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons

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    Brown, Maile R.; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H.

    2016-01-01

    Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express “high threshold” voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. PMID:27052580

  8. Assessment of Electrically Evoked Auditory Brain Stem Response of 30 Implanted Patients With Nucleus Multichannel Cochlear Implant

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    Dr. Soqrat Faghihzadeh

    2001-05-01

    Full Text Available Methods and Materials: Investigation of electrically evoked auditory brain stem response (EABR is a new issue, especially in implanted patients. Experiments were performed in C.I Center of Iranian Institute for Science and research expansion,1996 on 30 implanted patients with 22 spectra and MSP cochlear implant system and 30 normal subjects with the range of 3-33 years. Findings: I- EABR was obtained in the implanted patients. 2- Absolute latency of EABR waves is 1-1.5 ms shorter than ABR waves ‘P<0.05. 3-Absolute latency of wave V decreases as a function of electric stimulus magnitude (P<0.05. 4- No significant difference was observed in IPL Ill-V between ABR and EABR.

  9. Effect of middle ear effusion on the brain-stem auditory evoked response of Cavalier King Charles Spaniels.

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    Harcourt-Brown, Thomas R; Parker, John E; Granger, Nicolas; Jeffery, Nick D

    2011-06-01

    Brain-stem auditory evoked responses (BAER) were assessed in 23 Cavalier King Charles Spaniels with and without middle ear effusion at sound intensities ranging from 10 to 100 dB nHL. Significant differences were found between the median BAER threshold for ears where effusions were present (60 dB nHL), compared to those without (30 dB nHL) (P=0.001). The slopes of latency-intensity functions from both groups did not differ, but the y-axis intercept when the x value was zero was greater in dogs with effusions (P=0.009), consistent with conductive hearing loss. Analysis of latency-intensity functions suggested the degree of hearing loss due to middle ear effusion was 21 dB (95% confidence between 10 and 33 dB). Waves I-V inter-wave latency at 90 dB nHL was not significantly different between the two groups. These findings demonstrate that middle ear effusion is associated with a conductive hearing loss of 10-33 dB in affected dogs despite the fact that all animals studied were considered to have normal hearing by their owners. Copyright © 2010. Published by Elsevier Ltd.

  10. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

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    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. Copyright © 2016 the American Physiological Society.

  11. [Loss of brain stem auditory evoked potential waves I and II during controlled hypotension].

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    Papadopoulos, G; Lang, M; Link, J; Schäfer, M; Schaffartzik, W; Eyrich, K; Bornfeld, N; Foerster, M H

    1995-11-01

    For surgical removal of a malignant choroid melanoma, it is necessary to reduce systolic blood pressure to around 50-60 mmHg in order to prevent choroidal haemorrhages. However, blood pressure reduction is associated with the risk of cerebral ischaemia. We report a patient with a malignant choroid melanoma in whom waves I and II of the brainstem auditory evoked potentials (BAEP) disappeared during surgery under controlled arterial hypotension and hypothermia (31.1 degrees C). The waves could be recorded again immediately after the mean arterial pressure was increased from 48 to 77 mmHg. The oesophageal temperature had dropped by 0.3 degrees C at this time. The 2-channel electroencephalogram (EEG) showed no irregularities during this time period. A bilateral, reversible, apparently blood-pressure-dependent loss of waves I and II during arterial hypotension despite a normal EEG has to our knowledge not been previously described in the literature. The isolated loss of waves I and II with maintenance of waves III, IV, and V is unusual. The literature contains reports of acoustic neurinoma patients in whom only wave V could be recorded. This is regarded as an indication of continued impulse conduction despite the loss of waves I to IV. Others have observed a patient with temporary and reversible loss of BAEP wave I due to vasospasm of the internal auditory artery that apparently occurred during or shortly after manipulation of the internal auditory meatus. Assuming anatomic peculiarities in the blood supply to the generators of the BAEP waves, a stenosis of the basilar artery could be considered as the cause of the bilateral reversible loss of waves I and II. Another potential source could be induced hypothermia, but this does not seem very likely because the patient's temperature was 0.3 degrees C lower at the return of the waves than at their loss.

  12. [Increase in intracranial pressure in monitoring brain stem auditory evoked potentials using headphones].

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    Schwarz, G; Pfurtscheller, G; Tritthart, H; List, W F

    1988-11-01

    Ten measurements of intracranial pressure (ICP) (ventricular n = 5, epidural n = 3) in 8 patients (3 after aneurysm surgery, 5 with head trauma) were performed before and after application of conventional headphones for stimulating brainstem auditory evoked potentials (BAEP). The effects of miniature earphones and sound tubes on ICP were also studied. In 7 of 10 measurements after application of headphones a reversible increase of ICP (mean 26 +/- 19% in patients with ICP greater than 10 mmHg was recorded; in 3 patients (ICP less than or equal to 10 mgHg) no changes of ICP were seen. Using miniature earphones and sound tubes no increase of ICP was noted in any patient, and hence these can be recommended for stimulating BAEP in case of increased ICP.

  13. Evaluation of brain stem auditory evoked potentials in stable patients with chronic obstructive pulmonary disease

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    Gupta Prem

    2008-01-01

    Full Text Available Though there are few studies addressing brainstem auditory evoked potentials (BAEP in patients with chronic obstructive pulmonary disease (COPD, subclinical BAEP abnormalities in stable COPD patients have not been studied. The present study aimed to evaluate the BAEP abnormalities in this study group. Materials and Methods : In the present study, 80 male subjects were included: COPD group comprised 40 smokers with stable COPD with no clinical neuropathy; 40 age-matched healthy volunteers served as the control group. Latencies of BAEP waves I, II, III, IV, and V, together with interpeak latencies (IPLs of I-III, I-V, and III-V, and amplitudes of waves I-Ia and V-Va were studied in both the groups to compare the BAEP abnormalities in COPD group; the latter were correlated with patient characteristics and Mini-Mental Status Examination Questionnaire (MMSEQ scores to seek any significant correlation. Results: Twenty-six (65% of the 40 COPD patients had BAEP abnormalities. We observed significantly prolonged latencies of waves I, III, V over left ear and waves III, IV, V over right ear; increased IPLs of I-V, III-V over left ear and of I-III, I-V, III-V over right side. Amplitudes of waves I-Ia and V-Va were decreased bilaterally. Over left ear, the latencies of wave I and III were significantly correlated with FEV 1 ; and amplitude of wave I-Ia, with smoking pack years. A weak positive correlation between amplitude of wave I-Ia and duration of illness; and a weak negative correlation between amplitude of wave V-Va and MMSEQ scores were seen over right side. Conclusions : We observed significant subclinical BAEP abnormalities on electrophysiological evaluation in studied stable COPD male patients having mild-to-moderate airflow obstruction.

  14. Therapeutic potential of stem cells in auditory hair cell repair

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    Ryuji Hata

    2009-01-01

    Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

  15. A low-affinity antagonist reveals saturation and desensitization in mature synapses in the auditory brain stem.

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    Chanda, Soham; Xu-Friedman, Matthew A

    2010-04-01

    Postsynaptic receptor desensitization has been observed to contribute to depression in immature synapses. However, it is not clear whether desensitization persists and causes depression in mature synapses. We investigate this issue at the endbulb of Held, the synapse made by auditory nerve (AN) fibers onto bushy cells (BCs) of the anteroventral cochlear nucleus, where depression could influence the processing of sound information. Experiments using cyclothiazide (CTZ) have implicated desensitization in endbulbs from postnatal day 16 (P16) to P21 mice, but application of γ-D-glutamylglycine (DGG) did not reveal desensitization in endbulbs >P22. To reconcile these findings, we have studied the effects of both CTZ and DGG on endbulbs from P5 to P40 CBA/CaJ mice. In paired-pulse protocols, both CTZ and DGG reduced depression in all ages at intervals 20 ms, consistent with DGG's use to prevent saturation. DGG application revealed receptor saturation even under conditions of very low release probability. Preventing desensitization by CTZ occluded the effects of DGG on desensitization and revealed the effects of saturation at short intervals. We developed an approach to separate DGG's effect on saturation from its effect on desensitization, which showed that desensitization has an impact during bursts of auditory nerve activity. Dynamic-clamp experiments indicated that desensitization can reduce BC spike probability and increase latency and jitter. Thus desensitization may affect sound processing in the mature auditory system.

  16. Effect Of Electromagnetic Waves Emitted From Mobile Phone On Brain Stem Auditory Evoked Potential In Adult Males.

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    Singh, K

    2015-01-01

    Mobile phone (MP) is commonly used communication tool. Electromagnetic waves (EMWs) emitted from MP may have potential health hazards. So, it was planned to study the effect of electromagnetic waves (EMWs) emitted from the mobile phone on brainstem auditory evoked potential (BAEP) in male subjects in the age group of 20-40 years. BAEPs were recorded using standard method of 10-20 system of electrode placement and sound click stimuli of specified intensity, duration and frequency.Right ear was exposed to EMW emitted from MP for about 10 min. On comparison of before and after exposure to MP in right ear (found to be dominating ear), there was significant increase in latency of II, III (p wave, amplitude of I-Ia wave (p wave (P waves of BAEP in left ear before vs after MP. On comparison of right (having exposure routinely as found to be dominating ear) and left ears (not exposed to MP), before exposure to MP, IPL of IIl-V wave and amplitude of V-Va is more (wave (< 0.001) in left ear. After exposure to MP, the amplitude of V-Va was (p < 0.05) more in right ear compared to left ear. In conclusion, EMWs emitted from MP affects the auditory potential.

  17. Auditory brain-stem response, CT and MR imaging in a family with classical type Pelizaeus-Merzbacher Disease

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    Shiomi, M.; Ookuni, H.; Sugita, T.

    1987-05-01

    A family in which 5 males in successive generations were clinically suspected to be affected with the classical X-linked recessive form of Pelizaeus-Merzbacher disease (PMD) is presented. Two brothers and their maternal uncle were examined by one of the authors (MS). In two brothers, aged 3 years and 2 years, the disease became obvious within a month after birth with nystagmus and head tremor. Head control and sitting were achieved at the age of 18 months at which time they began to speak. They could not stand nor walk without support. They had dysmetria, weakness and hyper-reflexia of lower extremities, and mild mental retardation. Their maternal uncle, aged 37 years, showed psychomotor retardation from birth and subsequently developed spastic paraplegia. He had been able to walk with crutches until adolescence. He had dysmetria, scanning speech, athetoid posture of fingers and significant intellectual deficits. Auditory brainstem response in both brothers revealed well defined waves I and II, low amplitude wave III and an absence of all subsequent components. CT demonstrated mild cerebral atrophy in the elder brother and was normal in the younger brother, but in their uncle, CT showed atrophy of the brainstem, cerebellum and cerebrum, and low density of the white matter of the centrum semiovale. MRI was performed in both brothers. Although the brainstem, the internal capsule and the thalamus were myelinated, the myelination in the subcortical white matter was restricted to periventricular regions on IR sequence scans. On SE sequence, the subcortical white matter was imaged as a brighter area than the cerebral cortex. These results demonstrate that the degree of myelination in these patients was roughly equal to that of 3-to 6-month old infants.

  18. A Brain System for Auditory Working Memory.

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    Kumar, Sukhbinder; Joseph, Sabine; Gander, Phillip E; Barascud, Nicolas; Halpern, Andrea R; Griffiths, Timothy D

    2016-04-20

    The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance. Copyright © 2016 Kumar et al.

  19. Childhood Brain Stem Glioma Treatment

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    ... factors for brain stem glioma include: Having certain genetic disorders , such as neurofibromatosis type 1 (NF1). The signs and symptoms of brain stem glioma are not the same in every child. Signs ...

  20. Identification of neonatal hearing impairment: evaluation of transient evoked otoacoustic emission, distortion product otoacoustic emission, and auditory brain stem response test performance.

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    Norton, S J; Gorga, M P; Widen, J E; Folsom, R C; Sininger, Y; Cone-Wesson, B; Vohr, B R; Mascher, K; Fletcher, K

    2000-10-01

    The purpose of this study was to compare the performance of transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), and auditory brain stem responses (ABRs) as tools for identification of neonatal hearing impairment. A total of 4911 infants including 4478 graduates of neonatal intensive care units, 353 well babies with one or more risk factors for hearing loss (Joint Committee on Infant Hearing, 1994) and 80 well babies without risk factor who did not pass one or more neonatal test were targeted as the potential subject pool on which test performance would be assessed. During the neonatal period, they were evaluated using TEOAEs in response to an 80 dB pSPL click, DPOAE responses to two stimulus conditions (L1 = L2 = 75 dB SPL and L1 = 65 dB SPL L2 = 50 dB SPL), and ABR elicited by a 30 dB nHL click. In an effort to describe test performance, these "at-risk" infants were asked to return for behavioral audiologic assessments, using visual reinforcement audiometry (VRA) at 8 to 12 mo corrected age, regardless of neonatal test results. Sixty-four percent of these subjects returned and reliable VRA data were obtained on 95.6% of these returnees. This approach is in contrast to previous studies in which, by necessity, efforts were made to follow only those infants who "failed" the neonatal screening tests. The accuracy of the neonatal measures in predicting hearing status at 8 to 12 mo corrected age was determined. Only those infants who provided reliable, monaural VRA test results were included in the analysis. Separate analyses were performed without regard to intercurrent events (i.e., events between the neonatal and VRA tests that could cause their results to disagree), and then after accounting for the possible influence of intercurrent events such as otitis media and late-onset or progressive hearing loss. Low refer rates were achieved for the stopping criteria used in the present study, especially when a protocol

  1. Brain stem evoked response to forward and reversed speech in humans.

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    Galbraith, Gary C; Amaya, Elizabeth M; de Rivera, Jacinta M Diaz; Donan, Namee M; Duong, Mylien T; Hsu, Jeffrey N; Tran, Kim; Tsang, Lian P

    2004-09-15

    Speech stimuli played in reverse are perceived as unfamiliar and alien-sounding, even though phoneme duration and fundamental voicing frequency are preserved. Although language perception ultimately resides in the neocortex, the brain stem plays a vital role in processing auditory information, including speech. The present study measured brain stem frequency-following responses (FFR) evoked by forward and reverse speech stimuli recorded from electrodes oriented horizontally and vertically to measure signals with putative origins in auditory nerve and rostral brain stem, respectively. The vertical FFR showed increased amplitude due to forward speech. It is concluded that familiar phonological and prosodic properties of forward speech selectively activate central brain stem neurons.

  2. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis.

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    Ren, Hongmiao; Chen, Jichuan; Wang, Yinan; Zhang, Shichang; Zhang, Bo

    2013-01-01

    Stem cell-based regenerative therapy is a potential cellular therapeutic strategy for patients with incurable brain diseases. Embryonic neural stem cells (NSCs) represent an attractive cell source in regenerative medicine strategies in the treatment of diseased brains. Here, we assess the capability of intracerebral embryonic NSCs transplantation for C57BL/6J mice with presbycusis in vivo. Morphology analyses revealed that the neuronal rate of apoptosis was lower in the aged group (10 months of age) but not in the young group (2 months of age) after NSCs transplantation, while the electrophysiological data suggest that the Auditory Brain Stem Response (ABR) threshold was significantly decreased in the aged group at 2 weeks and 3 weeks after transplantation. By contrast, there was no difference in the aged group at 4 weeks post-transplantation or in the young group at any time post-transplantation. Furthermore, immunofluorescence experiments showed that NSCs differentiated into neurons that engrafted and migrated to the brain, even to sites of lesions. Together, our results demonstrate that NSCs transplantation improve the auditory of C57BL/6J mice with presbycusis.

  3. Opposite brain laterality in analogous auditory and visual tests.

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    Oltedal, Leif; Hugdahl, Kenneth

    2017-11-01

    Laterality for language processing can be assessed by auditory and visual tasks. Typically, a right ear/right visual half-field (VHF) advantage is observed, reflecting left-hemispheric lateralization for language. Historically, auditory tasks have shown more consistent and reliable results when compared to VHF tasks. While few studies have compared analogous tasks applied to both sensory modalities for the same participants, one such study by Voyer and Boudreau [(2003). Cross-modal correlation of auditory and visual language laterality tasks: a serendipitous finding. Brain Cogn, 53(2), 393-397] found opposite laterality for visual and auditory language tasks. We adapted an experimental paradigm based on a dichotic listening and VHF approach, and applied the combined language paradigm in two separate experiments, including fMRI in the second experiment to measure brain activation in addition to behavioural data. The first experiment showed a right-ear advantage for the auditory task, but a left half-field advantage for the visual task. The second experiment, confirmed the findings, with opposite laterality effects for the visual and auditory tasks. In conclusion, we replicate the finding by Voyer and Boudreau (2003) and support their interpretation that these visual and auditory language tasks measure different cognitive processes.

  4. The human brain maintains contradictory and redundant auditory sensory predictions.

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    Marika Pieszek

    Full Text Available Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants' task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound as well as violations of the visual-auditory prediction (i.e., an incongruent sound elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]. Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.

  5. Music and the auditory brain: where is the connection?

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    Israel eNelken

    2011-09-01

    Full Text Available Sound processing by the auditory system is understood in unprecedented details, even compared with sensory coding in the visual system. Nevertheless, we don't understand yet the way in which some of the simplest perceptual properties of sounds are coded in neuronal activity. This poses serious difficulties for linking neuronal responses in the auditory system and music processing, since music operates on abstract representations of sounds. Paradoxically, although perceptual representations of sounds most probably occur high in auditory system or even beyond it, neuronal responses are strongly affected by the temporal organization of sound streams even in subcortical stations. Thus, to the extent that music is organized sound, it is the organization, rather than the sound, which is represented first in the auditory brain.

  6. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

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    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  7. Brain metabolism during hallucination-like auditory stimulation in schizophrenia.

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    Guillermo Horga

    Full Text Available Auditory verbal hallucinations (AVH in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1 at rest and (2 during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia.

  8. Neural mechanisms of auditory categorization: from across brain areas to within local microcircuits

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    Joji eTsunada

    2014-06-01

    Full Text Available Categorization enables listeners to efficiently encode and respond to auditory stimuli. Behavioral evidence for auditory categorization has been well documented across a broad range of human and non-human animal species. Moreover, neural correlates of auditory categorization have been documented in a variety of different brain regions in the ventral auditory pathway, which is thought to underlie auditory-object processing and auditory perception. Here, we review and discuss how neural representations of auditory categories are transformed across different scales of neural organization in the ventral auditory pathway: from across different brain areas to within local microcircuits. We propose different neural transformations across different scales of neural organization in auditory categorization. Along the ascending auditory system in the ventral pathway, there is a progression in the encoding of categories from simple acoustic categories to categories for abstract information. On the other hand, in local microcircuits, different classes of neurons differentially compute categorical information.

  9. Brain tumor stem cell dancing

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2014-09-01

    Full Text Available Background. Issues regarding cancer stem cell (CSC movement are important in neurosphere biology as cell-cell or cell-environment interactions may have significant impacts on CSC differentiation and contribute to the heterogeneity of the neurosphere. Aims. Despite the growing body of literature data on the biology of brain tumor stem cells, floating CSC-derived neurospheres have been scarcely characterized from a morphological and ultrastructural point of view. Results. Here we report a morphological and ultrastructural characterization performed by live imaging and scanning electron microscopy. Glioblastoma multiforme (GBM CSC-derived neurospheres are heterogeneous and are constituted by cells, morphologically different, capable of forming highly dynamic structures. These dynamic structures are regulated by not serendipitous cell-cell interactions, and they synchronously pulsate following a cyclic course made of "fast" and "slow" alternate phases. Autocrine/paracrine non canonical Wnt signalling appears to be correlated with the association status of neurospheres. Conclusions. The results obtained suggest that GBM CSCs can behave both as independents cells and as "social" cells, highly interactive with other members of its species, giving rise to a sort of "multicellular organism".

  10. Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

    Science.gov (United States)

    Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

    2012-01-01

    Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

  11. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    OpenAIRE

    Qiao, Guanqun; Li, Qingquan; Peng, Gang; Ma, Jun; Fan, Hongwei; Li, Yingbin

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain t...

  12. Somatosensory and acoustic brain stem reflex myoclonus.

    OpenAIRE

    Shibasaki, H; Kakigi, R; Oda, K; Masukawa, S

    1988-01-01

    A patient with brain stem reflex myoclonus due to a massive midbrain infarct was studied electrophysiologically. Myoclonic jerks were elicited at variable latencies by tapping anywhere on the body or by acoustic stimuli, and mainly involved flexor muscles of upper extremities. The existence of convergence of somatosensory and acoustic inputs in the brain stem was suggested. This myoclonus seemed to be mediated by a mechanism similar to the spino-bulbo-spinal reflex.

  13. 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?

  14. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  15. The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks.

    Directory of Open Access Journals (Sweden)

    Sven eVanneste

    2012-05-01

    Full Text Available Tinnitus is the perception of a sound in the absence of an external sound source. It is characterized by sensory components such as the perceived loudness, the lateralization, the tinnitus type (pure tone, noise-like and associated emotional components, such as distress and mood changes. Source localization of qEEG data demonstrate the involvement of auditory brain areas as well as several non-auditory brain areas such as the anterior cingulate cortex (dorsal and subgenual, auditory cortex (primary and secondary, dorsal lateral prefrontal cortex, insula, supplementary motor area, orbitofrontal cortex (including the inferior frontal gyrus, parahippocampus, posterior cingulate cortex and the precuneus, in different aspects of tinnitus. Explaining these non-auditory brain areas as constituents of separable subnetworks, each reflecting a specific aspect of the tinnitus percept increases the explanatory power of the non-auditory brain areas involvement in tinnitus. Thus the unified percept of tinnitus can be considered an emergent property of multiple parallel dynamically changing and partially overlapping subnetworks, each with a specific spontaneous oscillatory pattern and functional connectivity signature.

  16. Neurofibromatosis type 1: brain stem tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bilaniuk, L.T. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Molloy, P.T. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Zimmerman, R.A. [Department of Radiology, The Children`s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA (United States); Phillips, P.C. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Vaughan, S.N. [Division of Neurology, Children`s Hospital of Philadelphia, PA (United States); Liu, G.T. [Division of Neuro-Ophthalmology, Children`s Hospital of Philadelphia, PA (United States); Sutton, L.N. [Division of Neurosurgery, Children`s Hospital of Philadelphia, PA (United States); Needle, M. [Division of Oncology, The Children`s Hospital of Philadelphia. PA (United States)

    1997-09-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs.

  17. Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

    Directory of Open Access Journals (Sweden)

    Sandra Hackelberg

    Full Text Available Impairment of spiral ganglion neurons (SGNs of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM, the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC were differentiated into neural precursor cells (NPCs and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus. To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

  18. Tinnitus alters resting state functional connectivity (RSFC in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS.

    Directory of Open Access Journals (Sweden)

    Juan San Juan

    Full Text Available Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex and non-region of interest (adjacent non-auditory cortices and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz, broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to

  19. Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS).

    Science.gov (United States)

    San Juan, Juan; Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

    2017-01-01

    Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom

  20. Breath-holding spells may be associated with maturational delay in myelination of brain stem.

    Science.gov (United States)

    Vurucu, Sebahattin; Karaoglu, Abdulbaki; Paksu, Sukru M; Oz, Oguzhan; Yaman, Halil; Gulgun, Mustafa; Babacan, Oguzhan; Unay, Bulent; Akin, Ridvan

    2014-02-01

    To evaluate possible contribution of maturational delay of brain stem in the etiology of breath-holding spells in children using brain stem auditory evoked potentials. The study group included children who experienced breath-holding spells. The control group consisted of healthy age- and sex-matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brain stem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brain stem auditory evoked potentials. The mean age of study and control groups was 26.3 ± 14.6 and 28.9 ± 13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared with the control group (2.07 ± 0.2 milliseconds; 1.92 ± 0.13 milliseconds and 4.00 ± 0.27 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.009 and P = 0.03, respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared with those of control group were significantly prolonged (2.09 ± 0.24 milliseconds; 1.92 ± 0.13 milliseconds and 4.04 ± 0.28 milliseconds; 3.83 ± 0.19 milliseconds; P = 0.007 and P = 0.01, respectively). Our results consider that maturational delay in myelination of brain stem may have a role in the etiology of breath-holding spells in children.

  1. Network Analysis of Functional Brain Connectivity Driven by Gamma-Band Auditory Steady-State Response in Auditory Hallucinations.

    Science.gov (United States)

    Ying, Jun; Zhou, Dan; Lin, Ke; Gao, Xiaorong

    The auditory steady-state response (ASSR) may reflect activity from different regions of the brain. Particularly, it was reported that the gamma-band ASSR plays an important role in working memory, speech understanding, and recognition. Traditionally, the ASSR has been determined by power spectral density analysis, which cannot detect the exact overall distributed properties of the ASSR. Functional network analysis has recently been applied in electroencephalography studies. Previous studies on resting or working state found a small-world organization of the brain network. Some researchers have studied dysfunctional networks caused by diseases. The present study investigates the brain connection networks of schizophrenia patients with auditory hallucinations during an ASSR task. A directed transfer function is utilized to estimate the brain connectivity patterns. Moreover, the structures of brain networks are analyzed by converting the connectivity matrices into graphs. It is found that for normal subjects, network connections are mainly distributed at the central and frontal-temporal regions. This indicates that the central regions act as transmission hubs of information under ASSR stimulation. For patients, network connections seem unordered. The finding that the path length was larger in patients compared to that in normal subjects under most thresholds provides insight into the structures of connectivity patterns. The results suggest that there are more synchronous oscillations that cover a long distance on the cortex but a less efficient network for patients with auditory hallucinations.

  2. [Verbal auditory agnosia: SPECT study of the brain].

    Science.gov (United States)

    Carmona, C; Casado, I; Fernández-Rojas, J; Garín, J; Rayo, J I

    1995-01-01

    Verbal auditory agnosia are rare in clinical practice. Clinically, it characterized by impairment of comprehension and repetition of speech but reading, writing, and spontaneous speech are preserved. So it is distinguished from generalized auditory agnosia by the preserved ability to recognize non verbal sounds. We present the clinical picture of a forty-years-old, right handed woman who developed verbal auditory agnosic after an bilateral temporal ischemic infarcts due to atrial fibrillation by dilated cardiomyopathie. Neurophysiological studies by pure tone threshold audiometry: brainstem auditory evoked potentials and cortical auditory evoked potentials showed sparing of peripheral hearing and intact auditory pathway in brainstem but impaired cortical responses. Cranial CT-SCAN revealed two large hypodenses area involving both cortico-subcortical temporal lobes. Cerebral SPECT using 99mTc-HMPAO as radiotracer showed hypoperfusion just posterior in both frontal lobes nect to Roland's fissure and at level of bitemporal lobes just anterior to Sylvian's fissure.

  3. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  4. Novel approaches to treating sensorineural hearing loss. Auditory genetics and necessary factors for stem cell transplant.

    Science.gov (United States)

    Vlastarakos, Petros V; Nikolopoulos, Thomas P; Tavoulari, Evangelia; Kiprouli, Catherine; Ferekidis, Eleftherios

    2008-08-01

    Sensorineural hearing loss is a chronic disease, with a serious impact on human communication and quality of life. Exposure to various factors can lead to irreversible hearing impairment, as the auditory epithelium in humans comprises terminally differentiated cells. By contrast, the inner ear of lower vertebrates and invertebrates shows regenerative capacity. Efforts to regenerate the damaged human inner ear may involve renewed cell proliferation, or transplanting cells that can differentiate into sensory cells. Literature review. Animal studies, in vitro studies, retrospective-cohort studies, community-based case-controls, clinical guidelines, and review articles. Embryonic stem cells, inner ear stem cells, and stem cells from other tissues (i.e., neural tissue, hematopoietic system) may be candidates for restoring the auditory epithelium. Transcriptional regulation of p27kip1 is the primary determinant of terminal mitosis and the final number of postmitotic progenitors of hair and supporting cells. Basic helix-loop-helix transcription factor Math1 was found to be necessary and sufficient for the production of auditory hair cells. Notch signaling seems to play a major role in the regulation of Math1, through lateral inhibition. Brn3c, Gfi1, and Barhl1 are also specific transcription factors that have been implicated in hair cell maintenance and consequent survival. Evidence concerning development, maintenance, and regeneration of hair cells is still at an embryonic stage. Combined data, as attempted in the present study, will lead to a more successful management of deafness.

  5. Cognitive factors shape brain networks for auditory skills: spotlight on auditory working memory.

    Science.gov (United States)

    Kraus, Nina; Strait, Dana L; Parbery-Clark, Alexandra

    2012-04-01

    Musicians benefit from real-life advantages, such as a greater ability to hear speech in noise and to remember sounds, although the biological mechanisms driving such advantages remain undetermined. Furthermore, the extent to which these advantages are a consequence of musical training or innate characteristics that predispose a given individual to pursue music training is often debated. Here, we examine biological underpinnings of musicians' auditory advantages and the mediating role of auditory working memory. Results from our laboratory are presented within a framework that emphasizes auditory working memory as a major factor in the neural processing of sound. Within this framework, we provide evidence for music training as a contributing source of these abilities. © 2012 New York Academy of Sciences.

  6. [Application of Brain-Boy Universal Professional in preliminary assessment of auditory processing disorder].

    Science.gov (United States)

    Rutkowska, Joanna; Łobaczuk-Sitnik, Anna; Kosztyła-Hojna, Bożena

    2017-09-29

    Increasing numbers of hearing pathology is auditory processing disorders. Auditory Processing Disorders (APD) are defined as difficulty in using auditory information to communicate and learn in the presence of normal peripheral hearing. It may be recognized as a problem with understanding of speech in noise and perception disorder of distorted speech. APD may accompany to articulation disorders, language problems and difficulties in reading and writing. The diagnosis of auditory processing disorders causes many difficulties primarily due to the lack of common testing procedures, precise criteria for qualification to the group of norm and pathology. The Brain-Boy Universal Professional (BUP) is one of diagnostics tools. It enables to assess the higher auditory functions. The aim of the study was preliminary assessment of hearing difficulties that may suggest the occurrence of auditory processing disorders in children. The questionnaire of hearing difficulties and BUP was used. Study includes 20 participants 2nd grade students of elementary school. The examination of the basic central functions was carried out with BUP. The parents and teacher complete the questionnaire to evaluate the hearing problems. Studies carried out indicate that the 40% schoolchild have hearing difficulties. The high percentage of deficits in auditory functions was confirmed with research results of medical device and the questionnaire for teacher. On the basis of the studies conducted may establish that the Warnke Method can serve as preliminary assessment of hearing difficulties that may suggest the occurrence of auditory processing disorders in children.

  7. Development of the brain stem in the rat. II. Thymidine-radiographic study of the time of origin of neurons of the upper medulla, excluding the vestibular and auditory nuclei.

    Science.gov (United States)

    Altman, J; Bayer, S A

    1980-11-01

    Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational days 12 and 13 (E12 + 13) until the day before birth (E21 + 22). In radiographs from adult progeny of these rats the proportion of neurons generated on specific days was determined in the major nuclei of the upper medulla, with the exception of the vestibular and auditory nuclei. The neurons of the motor nuclei are generated over a brief period. Neurons of the retrofacial nucleus are produced first, with more than 60% of the cells arising on day E11 or earlier. Peak generation time of abducens neurons is day E12 and of the neurons of the facial nucleus is day E13. In contrast, the neurons of the superior salivatory nucleus are produced late, predominantly on day E15 and some on day E16. The generation of the (sensory relay) neurons of the nucleus oralis of the trigeminal complex takes place over an extended period between days E12 and E15; the last generated cells include the largest neurons of this nucleus. Neurons of the raphe magnus are produced between days E11 and E14, the neurons of the rostral medullary reticular formation between days E12 and E15. The latest generated neurons of the upper medulla (excluding the cochlear nuclei) belong to a structure identified as the granular layer of the raphe. Combining these results with those of the preceding paper (Altman and Bayer, '80a) and with additional data, it is postulated that the laterally and ventrally situated motor nucleus of the trigeminal, the facial nucleus, and the nucleus ambiguous form a single longitudinal zone of branchial motor neurons with a rostral-to-caudal cytogenetic gradient. In contrast, the medially and dorsally situated (juxtaventricular) hypoglossal nucleus and abducens nucleus (together with the other nuclei of the ocular muscles) form a longitudinal somatic motor zone with a caudal-to-rostral gradient. The dorsal nucleus of the vagus and the superior salivatory nucleus may constitute

  8. Brain-speech alignment enhances auditory cortical responses and speech perception.

    Science.gov (United States)

    Saoud, Houda; Josse, Goulven; Bertasi, Eric; Truy, Eric; Chait, Maria; Giraud, Anne-Lise

    2012-01-04

    Asymmetry in auditory cortical oscillations could play a role in speech perception by fostering hemispheric triage of information across the two hemispheres. Due to this asymmetry, fast speech temporal modulations relevant for phonemic analysis could be best perceived by the left auditory cortex, while slower modulations conveying vocal and paralinguistic information would be better captured by the right one. It is unclear, however, whether and how early oscillation-based selection influences speech perception. Using a dichotic listening paradigm in human participants, where we provided different parts of the speech envelope to each ear, we show that word recognition is facilitated when the temporal properties of speech match the rhythmic properties of auditory cortices. We further show that the interaction between speech envelope and auditory cortices rhythms translates in their level of neural activity (as measured with fMRI). In the left auditory cortex, the neural activity level related to stimulus-brain rhythm interaction predicts speech perception facilitation. These data demonstrate that speech interacts with auditory cortical rhythms differently in right and left auditory cortex, and that in the latter, the interaction directly impacts speech perception performance.

  9. Prediction of Auditory and Visual P300 Brain-Computer Interface Aptitude

    Science.gov (United States)

    Halder, Sebastian; Hammer, Eva Maria; Kleih, Sonja Claudia; Bogdan, Martin; Rosenstiel, Wolfgang; Birbaumer, Niels; Kübler, Andrea

    2013-01-01

    Objective Brain-computer interfaces (BCIs) provide a non-muscular communication channel for patients with late-stage motoneuron disease (e.g., amyotrophic lateral sclerosis (ALS)) or otherwise motor impaired people and are also used for motor rehabilitation in chronic stroke. Differences in the ability to use a BCI vary from person to person and from session to session. A reliable predictor of aptitude would allow for the selection of suitable BCI paradigms. For this reason, we investigated whether P300 BCI aptitude could be predicted from a short experiment with a standard auditory oddball. Methods Forty healthy participants performed an electroencephalography (EEG) based visual and auditory P300-BCI spelling task in a single session. In addition, prior to each session an auditory oddball was presented. Features extracted from the auditory oddball were analyzed with respect to predictive power for BCI aptitude. Results Correlation between auditory oddball response and P300 BCI accuracy revealed a strong relationship between accuracy and N2 amplitude and the amplitude of a late ERP component between 400 and 600 ms. Interestingly, the P3 amplitude of the auditory oddball response was not correlated with accuracy. Conclusions Event-related potentials recorded during a standard auditory oddball session moderately predict aptitude in an audiory and highly in a visual P300 BCI. The predictor will allow for faster paradigm selection. Significance Our method will reduce strain on patients because unsuccessful training may be avoided, provided the results can be generalized to the patient population. PMID:23457444

  10. Prediction of auditory and visual p300 brain-computer interface aptitude.

    Directory of Open Access Journals (Sweden)

    Sebastian Halder

    Full Text Available OBJECTIVE: Brain-computer interfaces (BCIs provide a non-muscular communication channel for patients with late-stage motoneuron disease (e.g., amyotrophic lateral sclerosis (ALS or otherwise motor impaired people and are also used for motor rehabilitation in chronic stroke. Differences in the ability to use a BCI vary from person to person and from session to session. A reliable predictor of aptitude would allow for the selection of suitable BCI paradigms. For this reason, we investigated whether P300 BCI aptitude could be predicted from a short experiment with a standard auditory oddball. METHODS: Forty healthy participants performed an electroencephalography (EEG based visual and auditory P300-BCI spelling task in a single session. In addition, prior to each session an auditory oddball was presented. Features extracted from the auditory oddball were analyzed with respect to predictive power for BCI aptitude. RESULTS: Correlation between auditory oddball response and P300 BCI accuracy revealed a strong relationship between accuracy and N2 amplitude and the amplitude of a late ERP component between 400 and 600 ms. Interestingly, the P3 amplitude of the auditory oddball response was not correlated with accuracy. CONCLUSIONS: Event-related potentials recorded during a standard auditory oddball session moderately predict aptitude in an audiory and highly in a visual P300 BCI. The predictor will allow for faster paradigm selection. SIGNIFICANCE: Our method will reduce strain on patients because unsuccessful training may be avoided, provided the results can be generalized to the patient population.

  11. Interaction of language, auditory and memory brain networks in auditory verbal hallucinations.

    Science.gov (United States)

    Ćurčić-Blake, Branislava; Ford, Judith M; Hubl, Daniela; Orlov, Natasza D; Sommer, Iris E; Waters, Flavie; Allen, Paul; Jardri, Renaud; Woodruff, Peter W; David, Olivier; Mulert, Christoph; Woodward, Todd S; Aleman, André

    2017-01-01

    Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a symptom of other conditions and even in healthy people. Several current theories on the origin of AVH converge, with neuroimaging studies suggesting that the language, auditory and memory/limbic networks are of particular relevance. However, reconciliation of these theories with experimental evidence is missing. We review 50 studies investigating functional (EEG and fMRI) and anatomic (diffusion tensor imaging) connectivity in these networks, and explore the evidence supporting abnormal connectivity in these networks associated with AVH. We distinguish between functional connectivity during an actual hallucination experience (symptom capture) and functional connectivity during either the resting state or a task comparing individuals who hallucinate with those who do not (symptom association studies). Symptom capture studies clearly reveal a pattern of increased coupling among the auditory, language and striatal regions. Anatomical and symptom association functional studies suggest that the interhemispheric connectivity between posterior auditory regions may depend on the phase of illness, with increases in non-psychotic individuals and first episode patients and decreases in chronic patients. Leading hypotheses involving concepts as unstable memories, source monitoring, top-down attention, and hybrid models of hallucinations are supported in part by the published connectivity data, although several caveats and inconsistencies remain. Specifically, possible changes in fronto-temporal connectivity are still under debate. Precise hypotheses concerning the directionality of connections deduced from current theoretical approaches should be tested using experimental approaches that allow for discrimination of competing hypotheses. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  13. HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

    1988-01-01

    A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

  14. [Forensic application of brainstem auditory evoked potential in patients with brain concussion].

    Science.gov (United States)

    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 (Pbrain concussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

  15. Decoding the auditory brain with canonical component analysis

    DEFF Research Database (Denmark)

    de Cheveigné, Alain; Wong, Daniel; Di Liberto, Giovanni M

    2018-01-01

    The relation between a stimulus and the evoked brain response can shed light on perceptual processes within the brain. Signals derived from this relation can also be harnessed to control external devices for Brain Computer Interface (BCI) applications. While the classic event-related potential (ERP...... higher classification scores. CCA strips the brain response of variance unrelated to the stimulus, and the stimulus representation of variance that does not affect the response, and thus improves observations of the relation between stimulus and response....

  16. Turning down the noise: the benefit of musical training on the aging auditory brain.

    Science.gov (United States)

    Alain, Claude; Zendel, Benjamin Rich; Hutka, Stefanie; Bidelman, Gavin M

    2014-02-01

    Age-related decline in hearing abilities is a ubiquitous part of aging, and commonly impacts speech understanding, especially when there are competing sound sources. While such age effects are partially due to changes within the cochlea, difficulties typically exist beyond measurable hearing loss, suggesting that central brain processes, as opposed to simple peripheral mechanisms (e.g., hearing sensitivity), play a critical role in governing hearing abilities late into life. Current training regimens aimed to improve central auditory processing abilities have experienced limited success in promoting listening benefits. Interestingly, recent studies suggest that in young adults, musical training positively modifies neural mechanisms, providing robust, long-lasting improvements to hearing abilities as well as to non-auditory tasks that engage cognitive control. These results offer the encouraging possibility that musical training might be used to counteract age-related changes in auditory cognition commonly observed in older adults. Here, we reviewed studies that have examined the effects of age and musical experience on auditory cognition with an emphasis on auditory scene analysis. We infer that musical training may offer potential benefits to complex listening and might be utilized as a means to delay or even attenuate declines in auditory perception and cognition that often emerge later in life. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Sensory gating revisited: relation between brain oscillations and auditory evoked potentials in schizophrenia.

    Science.gov (United States)

    Brockhaus-Dumke, Anke; Mueller, Ralf; Faigle, Ulrich; Klosterkoetter, Joachim

    2008-02-01

    Disturbances of auditory information processing have repeatedly been shown in schizophrenia. To contribute to a better understanding of the neurophysiological underpinnings of habituation in auditory processing and its disturbance in schizophrenia we used three different approaches to analyze auditory evoked responses, namely phase-locking (PL) analyses, single trial amplitudes, and averaged event-related potentials (P50 and N100). Given that brain oscillations reflect the neuronal correlates of information processing we hypothesized that PL and amplitudes reflect even more essential parts of auditory processing than the averaged ERP responses. In 32 schizophrenia patients and 32 matched controls EEG was continuously recorded using an auditory paired click paradigm. PL of the lower frequency bands (alpha and theta) was significantly reduced in patients whereas no significant differences were present in higher frequencies (gamma and beta). Alpha and theta PL and amplitudes showed a marked increase after the first click and to a minor degree after the second one. This habituation was more prominent in controls whereas in schizophrenia patients the response to both clicks differed only slightly. N100 suppression was significantly reduced in schizophrenia patients whereas no group differences were present with respect to the P50. This corresponded to the finding that gamma mostly contributed to the prediction of the P50 response and theta mostly to the N100 response. Our data showed that analyzing phase and amplitude in single trials provides more information on auditory information processing and reflects differences between schizophrenia patients and controls better than analyzing the averaged ERP responses.

  18. Auditory evoked responses in musicians during passive vowel listening are modulated by functional connectivity between bilateral auditory-related brain regions.

    Science.gov (United States)

    Kühnis, Jürg; Elmer, Stefan; Jäncke, Lutz

    2014-12-01

    Currently, there is striking evidence showing that professional musical training can substantially alter the response properties of auditory-related cortical fields. Such plastic changes have previously been shown not only to abet the processing of musical sounds, but likewise spectral and temporal aspects of speech. Therefore, here we used the EEG technique and measured a sample of musicians and nonmusicians while the participants were passively exposed to artificial vowels in the context of an oddball paradigm. Thereby, we evaluated whether increased intracerebral functional connectivity between bilateral auditory-related brain regions may promote sensory specialization in musicians, as reflected by altered cortical N1 and P2 responses. This assumption builds on the reasoning that sensory specialization is dependent, at least in part, on the amount of synchronization between the two auditory-related cortices. Results clearly revealed that auditory-evoked N1 responses were shaped by musical expertise. In addition, in line with our reasoning musicians showed an overall increased intracerebral functional connectivity (as indexed by lagged phase synchronization) in theta, alpha, and beta bands. Finally, within-group correlative analyses indicated a relationship between intracerebral beta band connectivity and cortical N1 responses, however only within the musicians' group. Taken together, we provide first electrophysiological evidence for a relationship between musical expertise, auditory-evoked brain responses, and intracerebral functional connectivity among auditory-related brain regions.

  19. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Facchino, Sabrina; Abdouh, Mohamed [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Bernier, Gilbert, E-mail: gbernier.hmr@ssss.gouv.qc.ca [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Faculté de Médecine, Université de Montréal, Montréal, H3T 1J4 (Canada)

    2011-03-30

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

  20. Effects of scanner acoustic noise on intrinsic brain activity during auditory stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Yakunina, Natalia [Kangwon National University, Institute of Medical Science, School of Medicine, Chuncheon (Korea, Republic of); Kangwon National University Hospital, Neuroscience Research Institute, Chuncheon (Korea, Republic of); Kang, Eun Kyoung [Kangwon National University Hospital, Department of Rehabilitation Medicine, Chuncheon (Korea, Republic of); Kim, Tae Su [Kangwon National University Hospital, Department of Otolaryngology, Chuncheon (Korea, Republic of); Kangwon National University, School of Medicine, Department of Otolaryngology, Chuncheon (Korea, Republic of); Min, Ji-Hoon [University of Michigan, Department of Biopsychology, Cognition, and Neuroscience, Ann Arbor, MI (United States); Kim, Sam Soo [Kangwon National University Hospital, Neuroscience Research Institute, Chuncheon (Korea, Republic of); Kangwon National University, School of Medicine, Department of Radiology, Chuncheon (Korea, Republic of); Nam, Eui-Cheol [Kangwon National University Hospital, Neuroscience Research Institute, Chuncheon (Korea, Republic of); Kangwon National University, School of Medicine, Department of Otolaryngology, Chuncheon (Korea, Republic of)

    2015-10-15

    Although the effects of scanner background noise (SBN) during functional magnetic resonance imaging (fMRI) have been extensively investigated for the brain regions involved in auditory processing, its impact on other types of intrinsic brain activity has largely been neglected. The present study evaluated the influence of SBN on a number of intrinsic connectivity networks (ICNs) during auditory stimulation by comparing the results obtained using sparse temporal acquisition (STA) with those using continuous acquisition (CA). Fourteen healthy subjects were presented with classical music pieces in a block paradigm during two sessions of STA and CA. A volume-matched CA dataset (CAm) was generated by subsampling the CA dataset to temporally match it with the STA data. Independent component analysis was performed on the concatenated STA-CAm datasets, and voxel data, time courses, power spectra, and functional connectivity were compared. The ICA revealed 19 ICNs; the auditory, default mode, salience, and frontoparietal networks showed greater activity in the STA. The spectral peaks in 17 networks corresponded to the stimulation cycles in the STA, while only five networks displayed this correspondence in the CA. The dorsal default mode and salience networks exhibited stronger correlations with the stimulus waveform in the STA. SBN appeared to influence not only the areas of auditory response but also the majority of other ICNs, including attention and sensory networks. Therefore, SBN should be regarded as a serious nuisance factor during fMRI studies investigating intrinsic brain activity under external stimulation or task loads. (orig.)

  1. Bioelectrical brain effects of one's own voice identification in pitch of voice auditory feedback.

    Science.gov (United States)

    Korzyukov, Oleg; Bronder, Alexander; Lee, Yunseon; Patel, Sona; Larson, Charles R

    2017-07-01

    Control of voice fundamental frequency (F0) relies in part on comparison of the intended F0 level and auditory feedback. This comparison impacts "sense of agency", or SoA, commonly defined as being the agent of one's own actions and plays a key role for self-awareness and social interactions. SoA is aberrant in several psychiatric disorders. Knowledge about brain activity reflecting SoA can be used in clinical practice for these disorders. It was shown that perception of voice feedback as one's own voice, reflecting the recognition of SoA, alters auditory sensory processing. Using a voice perturbation paradigm we contrasted vocal and bioelectrical brain responses to auditory stimuli that differed in magnitude: 100 and 400 cents. Results suggest the different magnitudes were perceived as a pitch error in self-vocalization (100 cents) or as a pitch shift generated externally (400 cents). Vocalizations and neural responses to changes in pitch of self-vocalization were defined as those made to small magnitude pitch-shifts (100 cents) and which did not show differential neural responses to upward versus downward changes in voice pitch auditory feedback. Vocal responses to large magnitude pitch shifts (400 cents) were smaller than those made to small pitch shifts, and neural responses differed according to upwards versus downward changes in pitch. Our results suggest that the presence of SoA for self-produced sounds may modify bioelectrical brain responses reflecting differences in auditory processing of the direction of a pitch shift. We suggest that this modification of bioelectrical response can be used as a biological index of SoA. Possible neuronal mechanisms of this modification of bioelectrical brain response are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Brain activity during auditory and visual phonological, spatial and simple discrimination tasks.

    Science.gov (United States)

    Salo, Emma; Rinne, Teemu; Salonen, Oili; Alho, Kimmo

    2013-02-16

    We used functional magnetic resonance imaging to measure human brain activity during tasks demanding selective attention to auditory or visual stimuli delivered in concurrent streams. Auditory stimuli were syllables spoken by different voices and occurring in central or peripheral space. Visual stimuli were centrally or more peripherally presented letters in darker or lighter fonts. The participants performed a phonological, spatial or "simple" (speaker-gender or font-shade) discrimination task in either modality. Within each modality, we expected a clear distinction between brain activations related to nonspatial and spatial processing, as reported in previous studies. However, within each modality, different tasks activated largely overlapping areas in modality-specific (auditory and visual) cortices, as well as in the parietal and frontal brain regions. These overlaps may be due to effects of attention common for all three tasks within each modality or interaction of processing task-relevant features and varying task-irrelevant features in the attended-modality stimuli. Nevertheless, brain activations caused by auditory and visual phonological tasks overlapped in the left mid-lateral prefrontal cortex, while those caused by the auditory and visual spatial tasks overlapped in the inferior parietal cortex. These overlapping activations reveal areas of multimodal phonological and spatial processing. There was also some evidence for intermodal attention-related interaction. Most importantly, activity in the superior temporal sulcus elicited by unattended speech sounds was attenuated during the visual phonological task in comparison with the other visual tasks. This effect might be related to suppression of processing irrelevant speech presumably distracting the phonological task involving the letters. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Using auditory steady state responses to outline the functional connectivity in the tinnitus brain.

    Directory of Open Access Journals (Sweden)

    Winfried Schlee

    Full Text Available BACKGROUND: Tinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions. METHODS AND FINDINGS: Using whole-head magnetoencephalography we investigated cortical connectivity by means of phase synchronization in tinnitus subjects and healthy controls. We found evidence for a deviating pattern of long-range functional connectivity in tinnitus that was strongly correlated with individual ratings of the tinnitus percept. Phase couplings between the anterior cingulum and the right frontal lobe and phase couplings between the anterior cingulum and the right parietal lobe showed significant condition x group interactions and were correlated with the individual tinnitus distress ratings only in the tinnitus condition and not in the control conditions. CONCLUSIONS: To the best of our knowledge this is the first study that demonstrates existence of a global tinnitus network of long-range cortical connections outside the central auditory system. This result extends the current knowledge of how tinnitus is generated in the brain. We propose that this global extend of the tinnitus network is crucial for the continuos perception of the tinnitus tone and a therapeutical intervention that is able to change this network should result in relief of tinnitus.

  4. Neonatal bilateral diaphragmatic paralysis caused by brain stem haemorrhage.

    OpenAIRE

    Blazer, S; Hemli, J A; Sujov, P O; Braun, J.

    1989-01-01

    We describe a neonate with severe bilateral diaphragmatic paralysis caused by haemorrhage in the lower brain stem. To our knowledge this association has not been previously reported in the English medical literature.

  5. Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2012-01-15

    Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

  6. Localized Brain Activation Related to the Strength of Auditory Learning in a Parrot

    Science.gov (United States)

    Matsushita, Masanori; Matsuda, Yasushi; Takeuchi, Hiro-Aki; Satoh, Ryohei; Watanabe, Aiko; Zandbergen, Matthijs A.; Manabe, Kazuchika; Kawashima, Takashi; Bolhuis, Johan J.

    2012-01-01

    Parrots and songbirds learn their vocalizations from a conspecific tutor, much like human infants acquire spoken language. Parrots can learn human words and it has been suggested that they can use them to communicate with humans. The caudomedial pallium in the parrot brain is homologous with that of songbirds, and analogous to the human auditory association cortex, involved in speech processing. Here we investigated neuronal activation, measured as expression of the protein product of the immediate early gene ZENK, in relation to auditory learning in the budgerigar (Melopsittacus undulatus), a parrot. Budgerigar males successfully learned to discriminate two Japanese words spoken by another male conspecific. Re-exposure to the two discriminanda led to increased neuronal activation in the caudomedial pallium, but not in the hippocampus, compared to untrained birds that were exposed to the same words, or were not exposed to words. Neuronal activation in the caudomedial pallium of the experimental birds was correlated significantly and positively with the percentage of correct responses in the discrimination task. These results suggest that in a parrot, the caudomedial pallium is involved in auditory learning. Thus, in parrots, songbirds and humans, analogous brain regions may contain the neural substrate for auditory learning and memory. PMID:22701714

  7. Localized brain activation related to the strength of auditory learning in a parrot.

    Directory of Open Access Journals (Sweden)

    Hiroko Eda-Fujiwara

    Full Text Available Parrots and songbirds learn their vocalizations from a conspecific tutor, much like human infants acquire spoken language. Parrots can learn human words and it has been suggested that they can use them to communicate with humans. The caudomedial pallium in the parrot brain is homologous with that of songbirds, and analogous to the human auditory association cortex, involved in speech processing. Here we investigated neuronal activation, measured as expression of the protein product of the immediate early gene ZENK, in relation to auditory learning in the budgerigar (Melopsittacus undulatus, a parrot. Budgerigar males successfully learned to discriminate two Japanese words spoken by another male conspecific. Re-exposure to the two discriminanda led to increased neuronal activation in the caudomedial pallium, but not in the hippocampus, compared to untrained birds that were exposed to the same words, or were not exposed to words. Neuronal activation in the caudomedial pallium of the experimental birds was correlated significantly and positively with the percentage of correct responses in the discrimination task. These results suggest that in a parrot, the caudomedial pallium is involved in auditory learning. Thus, in parrots, songbirds and humans, analogous brain regions may contain the neural substrate for auditory learning and memory.

  8. Subacute sclerosing panencephalitis: brain stem involvement in a peculiar pattern

    Energy Technology Data Exchange (ETDEWEB)

    Senol, U. [Akdeniz University, Antalya (Turkey). Faculty of Medicine; Haspolat, S. [Akdeniz University, Antalya (Turkey). Dept. of Child Neurology; Cevikol, C. [Akdeniz University, Antalya (Turkey). Dept. of Radiodiagnostics; Saatci, I. [Hacettepe University (Turkey). Medical Faculty

    2000-12-01

    The most common pattern in subacute sclerosing panencephalitis, is in the cerebral hemisphere white matter on T2-weighted images with or without atrophy. Brain-stem lesions are rare. We report brain-stem involvement in two children with subacute sclerosing panencephalitis. A peculiar pattern, with involvement of the pons with extension to both middle cerebellar peduncles and substantia nigra but sparing the pontine tegmentum, is suggested. (orig.)

  9. Auditory and Cognitive Factors Associated with Speech-in-Noise Complaints following Mild Traumatic Brain Injury.

    Science.gov (United States)

    Hoover, Eric C; Souza, Pamela E; Gallun, Frederick J

    2017-04-01

    Auditory complaints following mild traumatic brain injury (MTBI) are common, but few studies have addressed the role of auditory temporal processing in speech recognition complaints. In this study, deficits understanding speech in a background of speech noise following MTBI were evaluated with the goal of comparing the relative contributions of auditory and nonauditory factors. A matched-groups design was used in which a group of listeners with a history of MTBI were compared to a group matched in age and pure-tone thresholds, as well as a control group of young listeners with normal hearing (YNH). Of the 33 listeners who participated in the study, 13 were included in the MTBI group (mean age = 46.7 yr), 11 in the Matched group (mean age = 49 yr), and 9 in the YNH group (mean age = 20.8 yr). Speech-in-noise deficits were evaluated using subjective measures as well as monaural word (Words-in-Noise test) and sentence (Quick Speech-in-Noise test) tasks, and a binaural spatial release task. Performance on these measures was compared to psychophysical tasks that evaluate monaural and binaural temporal fine-structure tasks and spectral resolution. Cognitive measures of attention, processing speed, and working memory were evaluated as possible causes of differences between MTBI and Matched groups that might contribute to speech-in-noise perception deficits. A high proportion of listeners in the MTBI group reported difficulty understanding speech in noise (84%) compared to the Matched group (9.1%), and listeners who reported difficulty were more likely to have abnormal results on objective measures of speech in noise. No significant group differences were found between the MTBI and Matched listeners on any of the measures reported, but the number of abnormal tests differed across groups. Regression analysis revealed that a combination of auditory and auditory processing factors contributed to monaural speech-in-noise scores, but the benefit of spatial separation was

  10. Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

    2014-10-01

    The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  11. Brainstem Evoked Potential Indices of Subcortical Auditory Processing After Mild Traumatic Brain Injury.

    Science.gov (United States)

    Vander Werff, Kathy R; Rieger, Brian

    The primary aim of this study was to assess subcortical auditory processing in individuals with chronic symptoms after mild traumatic brain injury (mTBI) by measuring auditory brainstem responses (ABRs) to standard click and complex speech stimuli. Consistent with reports in the literature of auditory problems after mTBI (despite normal-hearing thresholds), it was hypothesized that individuals with mTBI would have evidence of impaired neural encoding in the auditory brainstem compared to noninjured controls, as evidenced by delayed latencies and reduced amplitudes of ABR components. We further hypothesized that the speech-evoked ABR would be more sensitive than the click-evoked ABR to group differences because of its complex nature, particularly when recorded in a background noise condition. Click- and speech-ABRs were collected in 32 individuals diagnosed with mTBI in the past 3 to 18 months. All mTBI participants were experiencing ongoing injury symptoms for which they were seeking rehabilitation through a brain injury rehabilitation management program. The same data were collected in a group of 32 age- and gender-matched controls with no history of head injury. ABRs were recorded in both left and right ears for all participants in all conditions. Speech-ABRs were collected in both quiet and in a background of continuous 20-talker babble ipsilateral noise. Peak latencies and amplitudes were compared between groups and across subgroups of mTBI participants categorized by their behavioral auditory test performance. Click-ABR results were not significantly different between the mTBI and control groups. However, when comparing the control group to only those mTBI subjects with measurably decreased performance on auditory behavioral tests, small differences emerged, including delayed latencies for waves I, III, and V. Similarly, few significant group differences were observed for peak amplitudes and latencies of the speech-ABR when comparing at the whole group level

  12. Discrimination of timbre in early auditory responses of the human brain.

    Directory of Open Access Journals (Sweden)

    Jaeho Seol

    Full Text Available BACKGROUND: The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1-testing (S2 paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2 for both same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES: Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

  13. Atypical brain responses to auditory spatial cues in adults with autism spectrum disorder.

    Science.gov (United States)

    Lodhia, Veema; Hautus, Michael J; Johnson, Blake W; Brock, Jon

    2017-09-09

    The auditory processing atypicalities experienced by many individuals on the autism spectrum disorder might be understood in terms of difficulties parsing the sound energy arriving at the ears into discrete auditory 'objects'. Here, we asked whether autistic adults are able to make use of two important spatial cues to auditory object formation - the relative timing and amplitude of sound energy at the left and right ears. Using electroencephalography, we measured the brain responses of 15 autistic adults and 15 age- and verbal-IQ-matched control participants as they listened to dichotic pitch stimuli - white noise stimuli in which interaural timing or amplitude differences applied to a narrow frequency band of noise typically lead to the perception of a pitch sound that is spatially segregated from the noise. Responses were contrasted with those to stimuli in which timing and amplitude cues were removed. Consistent with our previous studies, autistic adults failed to show a significant object-related negativity (ORN) for timing-based pitch, although their ORN was not significantly smaller than that of the control group. Autistic participants did show an ORN to amplitude cues, indicating that they do not experience a general impairment in auditory object formation. However, their P400 response - thought to indicate the later attention-dependent aspects of auditory object formation - was missing. These findings provide further evidence of atypical auditory object processing in autism with potential implications for understanding the perceptual and communication difficulties associated with the condition. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. The TLC: A Novel Auditory Nucleus of the Mammalian Brain

    OpenAIRE

    Saldaña Fernández, Enrique; Viñuela, Antonio; Marshall, Allen F.; Fitzpatrick, Douglas C.; Aparicio Vaquero, María Auxiliadora

    2007-01-01

    [EN]We have identified a novel nucleus of the mammalian brain and termed it the tectal longitudinal column (TLC). Basic histologic stains, tract-tracing techniques and three-dimensional reconstructions reveal that the rat TLC is a narrow, elongated structure spanning themidbrain tectum longitudinally. This paired nucleus is located close to the midline, immediately dorsal to the periaqueductal gray matter.It occupies what has traditionally been considered the most medial region of the deep su...

  15. Brain stem hypoplasia associated with Cri-du-Chat syndrome.

    Science.gov (United States)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  16. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2013-12-15

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  17. Brain Stem Hypoplasia Associated with Cri-du-Chat Syndrome

    OpenAIRE

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for th...

  18. The role of event-related brain potentials in assessing central auditory processing.

    Science.gov (United States)

    Alain, Claude; Tremblay, Kelly

    2007-01-01

    The perception of complex acoustic signals such as speech and music depends on the interaction between peripheral and central auditory processing. As information travels from the cochlea to primary and associative auditory cortices, the incoming sound is subjected to increasingly more detailed and refined analysis. These various levels of analyses are thought to include low-level automatic processes that detect, discriminate and group sounds that are similar in physical attributes such as frequency, intensity, and location as well as higher-level schema-driven processes that reflect listeners' experience and knowledge of the auditory environment. In this review, we describe studies that have used event-related brain potentials in investigating the processing of complex acoustic signals (e.g., speech, music). In particular, we examine the role of hearing loss on the neural representation of sound and how cognitive factors and learning can help compensate for perceptual difficulties. The notion of auditory scene analysis is used as a conceptual framework for interpreting and studying the perception of sound.

  19. Study on diffusion tensor imaging combined with electrophysiological monitoring in brain stem cavernous hemangioma resection

    Directory of Open Access Journals (Sweden)

    Dong-sheng KONG

    2017-07-01

    Full Text Available Objective To evaluate the clinical application value of diffusion tensor imaging (DTI combined with electrophysiological monitoring in the resection of brain stem cavernous hemangioma (CM.    Methods There were 39 patients with brain stem cavernous hemangioma. DTI was performed before and during the operation. Diffusion tensor tractography (DTT was used to track fiber and reconstruct pyramidal tract. Intraoperative neurobehavioral monitoring was used to detect the changes of somatosensory-evoked potentials (SEP, motor - evoked potentials (MEP and brain stem auditory - evoked potentials (BAEP.    Results Of all the 39 patients, there was no significant change of BAEP during the operation, 5 patients (12.82% had abnormal SEP, 6 cases (15.38% had abnormalities in MEP monitoring, 2 cases (5.13% had reduced volumes of pyramidal tract proved by DTI. Intraoperative MRI confirmed 36 cases (92.31% had complete removal of lesions, and 3 cases (7.69% had subtotal resection. There were improvement of clinical symptoms in 29 cases (74.36% , no obvious changes in 4 cases (10.26% , postoperative facial paralysis in 3 cases (7.69%, worsened movement disorder in 2 cases (5.13%, death due to disorder of consciousness and pulmonary infection in one case (2.56% . Postoperative follow - up was 30 months in average. Glasgow Outcome Scale (GOS showed 27 cases (69.23% of Grade 5, 7 cases (17.95% of Grade 4, 4 cases (10.26% of Grade 3, and one case (2.56% of Grade 1.    Conclusions Combined use of intraoperative DTI and electrophysiological monitoring can safely and effectively remove brain stem cavernous hemangioma. DOI: 10.3969/j.issn.1672-6731.2017.05.010

  20. Can you hear me now? Musical training shapes functional brain networks for selective auditory attention and hearing speech in noise.

    Science.gov (United States)

    Strait, Dana L; Kraus, Nina

    2011-01-01

    Even in the quietest of rooms, our senses are perpetually inundated by a barrage of sounds, requiring the auditory system to adapt to a variety of listening conditions in order to extract signals of interest (e.g., one speaker's voice amidst others). Brain networks that promote selective attention are thought to sharpen the neural encoding of a target signal, suppressing competing sounds and enhancing perceptual performance. Here, we ask: does musical training benefit cortical mechanisms that underlie selective attention to speech? To answer this question, we assessed the impact of selective auditory attention on cortical auditory-evoked response variability in musicians and non-musicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not non-musicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work documenting perceptual and subcortical advantages in musicians for the hearing and neural encoding of speech in background noise. Musicians' neural proficiency for selectively engaging and sustaining auditory attention to language indicates a potential benefit of music for auditory training. Given the importance of auditory attention for the development and maintenance of language-related skills, musical training may aid in the prevention, habilitation, and remediation of individuals with a wide range of attention-based language, listening and learning impairments.

  1. Can you hear me now? Musical training shapes functional brain networks for selective auditory attention and hearing speech in noise

    Directory of Open Access Journals (Sweden)

    Dana L Strait

    2011-06-01

    Full Text Available Even in the quietest of rooms, our senses are perpetually inundated by a barrage of sounds, requiring the auditory system to adapt to a variety of listening conditions in order to extract signals of interest (e.g., one speaker’s voice amidst others. Brain networks that promote selective attention are thought to sharpen the neural encoding of a target signal, suppressing competing sounds and enhancing perceptual performance. Here, we ask: does musical training benefit cortical mechanisms that underlie selective attention to speech? To answer this question, we assessed the impact of selective auditory attention on cortical auditory-evoked response variability in musicians and nonmusicians. Outcomes indicate strengthened brain networks for selective auditory attention in musicians in that musicians but not nonmusicians demonstrate decreased prefrontal response variability with auditory attention. Results are interpreted in the context of previous work from our laboratory documenting perceptual and subcortical advantages in musicians for the hearing and neural encoding of speech in background noise. Musicians’ neural proficiency for selectively engaging and sustaining auditory attention to language indicates a potential benefit of music for auditory training. Given the importance of auditory attention for the development of language-related skills, musical training may aid in the prevention, habilitation and remediation of children with a wide range of attention-based language and learning impairments.

  2. Differential maturation of brain signal complexity in the human auditory and visual system

    Directory of Open Access Journals (Sweden)

    Sarah Lippe

    2009-11-01

    Full Text Available Brain development carries with it a large number of structural changes at the local level which impact on the functional interactions of distributed neuronal networks for perceptual processing. Such changes enhance information processing capacity, which can be indexed by estimation of neural signal complexity. Here, we show that during development, EEG signal complexity increases from one month to 5 years of age in response to auditory and visual stimulation. However, the rates of change in complexity were not equivalent for the two responses. Infants’ signal complexity for the visual condition was greater than auditory signal complexity, whereas adults showed the same level of complexity to both types of stimuli. The differential rates of complexity change may reflect a combination of innate and experiential factors on the structure and function of the two sensory systems.

  3. The presence of family during brain stem death testing.

    Science.gov (United States)

    Doran, Majella

    2004-02-01

    Prior to 1959, cardiac and respiratory cessation was universally and unambiguously accepted as confirming the death of a person [M. Morioka, J. Clin. Nurs. 10 (2001) 132; Reconsidering brain death: a lesson from Japan's fifteen years of experience, 2001, http://proquest.umi.com/pqdweb]. However, with the rapid pace of modern technology and resuscitation techniques, the boundaries between life and death have become blurred [J. Bothamley, Organ donation: brain stem death, 2000, http://proquest.umi.com/pqdweb; Re-examining death: against a higher brain criterion, 1999, http://proquest.umi.com/pqdweb]. As a result, a redefinition of death, "brain death" has emerged [M. Brazier, Medicine, Patients and the Law, New ed., Penquin Books, London, 1992]. Most families faced with the brain stem death of a relative find the concept difficult to understand and have trouble in accepting that their relative is actually dead. In Part One of this two part series, the needs of families who are facing the brain stem death of a family member will be examined and explanations offered as to why families find the concept difficult to grasp. In addition, it will also advocate that family members are given the choice to be or not to be present during brain stem death testing. It is suggested that the presence of family members during brain stem death testing not only helps families to accept this concept of death but also promotes the grieving process. In Part Two, the barriers that inhibit family involvement and presence will be explored and methods for involving family proposed.

  4. Psychophysical and neural correlates of noised-induced tinnitus in animals: Intra- and inter-auditory and non-auditory brain structure studies.

    Science.gov (United States)

    Zhang, Jinsheng; Luo, Hao; Pace, Edward; Li, Liang; Liu, Bin

    2016-04-01

    Tinnitus, a ringing in the ear or head without an external sound source, is a prevalent health problem. It is often associated with a number of limbic-associated disorders such as anxiety, sleep disturbance, and emotional distress. Thus, to investigate tinnitus, it is important to consider both auditory and non-auditory brain structures. This paper summarizes the psychophysical, immunocytochemical and electrophysiological evidence found in rats or hamsters with behavioral evidence of tinnitus. Behaviorally, we tested for tinnitus using a conditioned suppression/avoidance paradigm, gap detection acoustic reflex behavioral paradigm, and our newly developed conditioned licking suppression paradigm. Our new tinnitus behavioral paradigm requires relatively short baseline training, examines frequency specification of tinnitus perception, and achieves sensitive tinnitus testing at an individual level. To test for tinnitus-related anxiety and cognitive impairment, we used the elevated plus maze and Morris water maze. Our results showed that not all animals with tinnitus demonstrate anxiety and cognitive impairment. Immunocytochemically, we found that animals with tinnitus manifested increased Fos-like immunoreactivity (FLI) in both auditory and non-auditory structures. The manner in which FLI appeared suggests that lower brainstem structures may be involved in acute tinnitus whereas the midbrain and cortex are involved in more chronic tinnitus. Meanwhile, animals with tinnitus also manifested increased FLI in non-auditory brain structures that are involved in autonomic reactions, stress, arousal and attention. Electrophysiologically, we found that rats with tinnitus developed increased spontaneous firing in the auditory cortex (AC) and amygdala (AMG), as well as intra- and inter-AC and AMG neurosynchrony, which demonstrate that tinnitus may be actively produced and maintained by the interactions between the AC and AMG. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The Wellcome Prize Lecture. A map of auditory space in the mammalian brain: neural computation and development.

    Science.gov (United States)

    King, A J

    1993-09-01

    The experiments described in this review have demonstrated that the SC contains a two-dimensional map of auditory space, which is synthesized within the brain using a combination of monaural and binaural localization cues. There is also an adaptive fusion of auditory and visual space in this midbrain nucleus, providing for a common access to the motor pathways that control orientation behaviour. This necessitates a highly plastic relationship between the visual and auditory systems, both during postnatal development and in adult life. Because of the independent mobility of difference sense organs, gating mechanisms are incorporated into the auditory representation to provide up-to-date information about the spatial orientation of the eyes and ears. The SC therefore provides a valuable model system for studying a number of important issues in brain function, including the neural coding of sound location, the co-ordination of spatial information between different sensory systems, and the integration of sensory signals with motor outputs.

  6. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...... receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...

  7. Tactile and bone-conduction auditory brain computer interface for vision and hearing impaired users.

    Science.gov (United States)

    Rutkowski, Tomasz M; Mori, Hiromu

    2015-04-15

    The paper presents a report on the recently developed BCI alternative for users suffering from impaired vision (lack of focus or eye-movements) or from the so-called "ear-blocking-syndrome" (limited hearing). We report on our recent studies of the extents to which vibrotactile stimuli delivered to the head of a user can serve as a platform for a brain computer interface (BCI) paradigm. In the proposed tactile and bone-conduction auditory BCI novel multiple head positions are used to evoke combined somatosensory and auditory (via the bone conduction effect) P300 brain responses, in order to define a multimodal tactile and bone-conduction auditory brain computer interface (tbcaBCI). In order to further remove EEG interferences and to improve P300 response classification synchrosqueezing transform (SST) is applied. SST outperforms the classical time-frequency analysis methods of the non-linear and non-stationary signals such as EEG. The proposed method is also computationally more effective comparing to the empirical mode decomposition. The SST filtering allows for online EEG preprocessing application which is essential in the case of BCI. Experimental results with healthy BCI-naive users performing online tbcaBCI, validate the paradigm, while the feasibility of the concept is illuminated through information transfer rate case studies. We present a comparison of the proposed SST-based preprocessing method, combined with a logistic regression (LR) classifier, together with classical preprocessing and LDA-based classification BCI techniques. The proposed tbcaBCI paradigm together with data-driven preprocessing methods are a step forward in robust BCI applications research. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  9. Simultaneous EEG-fMRI brain signatures of auditory cue utilization

    Directory of Open Access Journals (Sweden)

    Mathias eScharinger

    2014-06-01

    Full Text Available Optimal utilization of acoustic cues during auditory categorization is a vital skill, particularly when informative cues become occluded or degraded. Consequently, the acoustic environment requires flexible choosing and switching amongst available cues. The present study targets the brain functions underlying such changes in cue utilization. Participants performed a categorization task with immediate feedback on acoustic stimuli from two categories that varied in duration and spectral properties, while we simultaneously recorded Blood Oxygenation Level Dependent (BOLD responses in fMRI and electroencephalograms (EEGs. In the first half of the experiment, categories could be best discriminated by spectral properties. Halfway through the experiment, spectral degradation rendered the stimulus duration the more informative cue. Behaviorally, degradation decreased the likelihood of utilizing spectral cues. Spectrally degrading the acoustic signal led to increased alpha power compared to nondegraded stimuli. The EEG-informed fMRI analyses revealed that alpha power correlated with BOLD changes in inferior parietal cortex and right posterior superior temporal gyrus (including planum temporale. In both areas, spectral degradation led to a weaker coupling of BOLD response to behavioral utilization of the spectral cue. These data provide converging evidence from behavioral modeling, electrophysiology, and hemodynamics that (a increased alpha power mediates the inhibition of uninformative (here spectral stimulus features, and that (b the parietal attention network supports optimal cue utilization in auditory categorization. The results highlight the complex cortical processing of auditory categorization under realistic listening challenges.

  10. Brain responses to altered auditory feedback during musical keyboard production: an fMRI study.

    Science.gov (United States)

    Pfordresher, Peter Q; Mantell, James T; Brown, Steven; Zivadinov, Robert; Cox, Jennifer L

    2014-03-27

    Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca's area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. An Auditory-Tactile Visual Saccade-Independent P300 Brain-Computer Interface.

    Science.gov (United States)

    Yin, Erwei; Zeyl, Timothy; Saab, Rami; Hu, Dewen; Zhou, Zongtan; Chau, Tom

    2016-02-01

    Most P300 event-related potential (ERP)-based brain-computer interface (BCI) studies focus on gaze shift-dependent BCIs, which cannot be used by people who have lost voluntary eye movement. However, the performance of visual saccade-independent P300 BCIs is generally poor. To improve saccade-independent BCI performance, we propose a bimodal P300 BCI approach that simultaneously employs auditory and tactile stimuli. The proposed P300 BCI is a vision-independent system because no visual interaction is required of the user. Specifically, we designed a direction-congruent bimodal paradigm by randomly and simultaneously presenting auditory and tactile stimuli from the same direction. Furthermore, the channels and number of trials were tailored to each user to improve online performance. With 12 participants, the average online information transfer rate (ITR) of the bimodal approach improved by 45.43% and 51.05% over that attained, respectively, with the auditory and tactile approaches individually. Importantly, the average online ITR of the bimodal approach, including the break time between selections, reached 10.77 bits/min. These findings suggest that the proposed bimodal system holds promise as a practical visual saccade-independent P300 BCI.

  12. Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise.

    Directory of Open Access Journals (Sweden)

    Christos I Ioannou

    Full Text Available The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB. The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies.

  13. Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise

    Science.gov (United States)

    Ioannou, Christos I.; Pereda, Ernesto; Lindsen, Job P.; Bhattacharya, Joydeep

    2015-01-01

    The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB). The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min) of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha) binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies. PMID:26065708

  14. Research of brain activation regions of "yes" and "no" responses by auditory stimulations in human EEG

    Science.gov (United States)

    Hu, Min; Liu, GuoZhong

    2011-11-01

    People with neuromuscular disorders are difficult to communicate with the outside world. It is very important to the clinician and the patient's family that how to distinguish vegetative state (VS) and minimally conscious state (MCS) for a disorders of consciousness (DOC) patient. If a patient is diagnosed with VS, this means that the hope of recovery is greatly reduced, thus leading to the family to abandon the treatment. Brain-computer interface (BCI) is aiming to help those people by analyzing patients' electroencephalogram (EEG). This paper focus on analyzing the corresponding activated regions of the brain when a subject responses "yes" or "no" to an auditory stimuli question. When the brain concentrates, the phase of the related area will become orderly from desultorily. So in this paper we analyzed EEG from the angle of phase. Seven healthy subjects volunteered to participate in the experiment. A total of 84 groups of repeatability stimulation test were done. Firstly, the frequency is fragmented by using wavelet method. Secondly, the phase of EEG is extracted by Hilbert. At last, we obtained approximate entropy and information entropy of each frequency band of EEG. The results show that brain areas are activated of the central area when people say "yes", and the areas are activated of the central area and temporal when people say "no". This conclusion is corresponding to magnetic resonance imaging technology. This study provides the theory basis and the algorithm design basis for designing BCI equipment for people with neuromuscular disorders.

  15. Pathological and immunohistochemical study of lethal primary brain stem injuries

    Directory of Open Access Journals (Sweden)

    Rongchao Sun

    2012-05-01

    Full Text Available Abstract Background Many of the deaths that occur shortly after injury or in hospitals are caused by mild trauma. Slight morphological changes are often found in the brain stems of these patients during autopsy. The purpose of this study is to investigate the histopathological changes involved in primary brain stem injuries (PBSI and their diagnostic significance. Methods A total of 65 patients who had died of PBSI and other conditions were randomly selected. They were divided into 2 groups, an injury group (25 cases and a control group (20 cases. Slides of each patient’s midbrain, pons, and medulla oblongata were prepared and stained with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-ß, MBP. Under low power (×100 and NF staining, the diameter of the thickest longitudinal axon was measured at its widest point. Ten such diameters were collected for each part of the brain (midbrain, pons, and medulla oblongata. Data were recorded and analyzed statistically. Results Brain stem contusions, astrocyte activity, edema, and pathological changes in the neurons were visibly different in the injury and control groups (P P  Conclusions These histopathological changes may prove beneficial to the pathological diagnosis of PBSI during autopsy. The measurement of axon diameters provides a referent quantitative index for the diagnosis of the specific causes of death involved in PBSI. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1345298818712204

  16. Auditory-evoked cortical activity: contribution of brain noise, phase locking, and spectral power.

    Science.gov (United States)

    Harris, Kelly C; Vaden, Kenneth I; Dubno, Judy R

    2014-09-01

    The N1-P2 is an obligatory cortical response that can reflect the representation of spectral and temporal characteristics of an auditory stimulus. Traditionally,mean amplitudes and latencies of the prominent peaks in the averaged response are compared across experimental conditions. Analyses of the peaks in the averaged response only reflect a subset of the data contained within the electroencephalogram(EEG) signal. We used single-trial analyses techniques to identify the contribution of brain noise,neural synchrony, and spectral power to the generation of P2 amplitude and how these variables may change across age group. This information is important for appropriate interpretation of event-related potentials (ERPs) results and in understanding of age-related neural pathologies. EEG was measured from 25 younger and 25 older normal hearing adults. Age-related and individual differences in P2 response amplitudes, and variability in brain noise, phase locking value (PLV), and spectral power (4-8 Hz) were assessed from electrode FCz. Model testing and linear regression were used to determine the extent to which brain noise, PLV, and spectral power uniquely predicted P2 amplitudes and varied by age group. Younger adults had significantly larger P2 amplitudes, PLV, and power compared to older adults. Brain noise did not differ between age groups. The results of regression testing revealed that brain noise and PLV, but not spectral power were unique predictors of P2 amplitudes. Model fit was significantly better in younger than in older adults. ERP analyses are intended to provide a better understanding of the underlying neural mechanisms that contribute to individual and group differences in behavior. The current results support that age-related declines in neural synchrony contribute to smaller P2 amplitudes in older normal hearing adults. Based on our results, we discuss potential models in which differences in neural synchrony and brain noise can account for

  17. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  18. Exploring combinations of auditory and visual stimuli for gaze-independent brain-computer interfaces.

    Directory of Open Access Journals (Sweden)

    Xingwei An

    Full Text Available For Brain-Computer Interface (BCI systems that are designed for users with severe impairments of the oculomotor system, an appropriate mode of presenting stimuli to the user is crucial. To investigate whether multi-sensory integration can be exploited in the gaze-independent event-related potentials (ERP speller and to enhance BCI performance, we designed a visual-auditory speller. We investigate the possibility to enhance stimulus presentation by combining visual and auditory stimuli within gaze-independent spellers. In this study with N = 15 healthy users, two different ways of combining the two sensory modalities are proposed: simultaneous redundant streams (Combined-Speller and interleaved independent streams (Parallel-Speller. Unimodal stimuli were applied as control conditions. The workload, ERP components, classification accuracy and resulting spelling speed were analyzed for each condition. The Combined-speller showed a lower workload than uni-modal paradigms, without the sacrifice of spelling performance. Besides, shorter latencies, lower amplitudes, as well as a shift of the temporal and spatial distribution of discriminative information were observed for Combined-speller. These results are important and are inspirations for future studies to search the reason for these differences. For the more innovative and demanding Parallel-Speller, where the auditory and visual domains are independent from each other, a proof of concept was obtained: fifteen users could spell online with a mean accuracy of 87.7% (chance level <3% showing a competitive average speed of 1.65 symbols per minute. The fact that it requires only one selection period per symbol makes it a good candidate for a fast communication channel. It brings a new insight into the true multisensory stimuli paradigms. Novel approaches for combining two sensory modalities were designed here, which are valuable for the development of ERP-based BCI paradigms.

  19. Auditory agnosia.

    Science.gov (United States)

    Slevc, L Robert; Shell, Alison R

    2015-01-01

    Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition. © 2015 Elsevier B.V. All rights reserved.

  20. Affective Stimuli for an Auditory P300 Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Akinari Onishi

    2017-09-01

    Full Text Available Gaze-independent brain computer interfaces (BCIs are a potential communication tool for persons with paralysis. This study applies affective auditory stimuli to investigate their effects using a P300 BCI. Fifteen able-bodied participants operated the P300 BCI, with positive and negative affective sounds (PA: a meowing cat sound, NA: a screaming cat sound. Permuted stimuli of the positive and negative affective sounds (permuted-PA, permuted-NA were also used for comparison. Electroencephalography data was collected, and offline classification accuracies were compared. We used a visual analog scale (VAS to measure positive and negative affective feelings in the participants. The mean classification accuracies were 84.7% for PA and 67.3% for permuted-PA, while the VAS scores were 58.5 for PA and −12.1 for permuted-PA. The positive affective stimulus showed significantly higher accuracy and VAS scores than the negative affective stimulus. In contrast, mean classification accuracies were 77.3% for NA and 76.0% for permuted-NA, while the VAS scores were −50.0 for NA and −39.2 for permuted NA, which are not significantly different. We determined that a positive affective stimulus with accompanying positive affective feelings significantly improved BCI accuracy. Additionally, an ALS patient achieved 90% online classification accuracy. These results suggest that affective stimuli may be useful for preparing a practical auditory BCI system for patients with disabilities.

  1. Brain tissue banking for stem cells for our future.

    Science.gov (United States)

    Palmero, Emily; Palmero, Sheryl; Murrell, Wayne

    2016-12-19

    In our lab we study neurogenesis and the development of brain tumors. We work towards treatment strategies for glioblastoma and towards using autologous neural stem cells for tissue regeneration strategies for brain damage and neurodegenerative disorders. It has been our policy to try to establish living cell cultures from all human biopsy material that we obtain. We hypothesized that small pieces of brain tissue could be cryopreserved and that live neural stem cells could be recovered at a later time. DMSO has been shown to possess a remarkable ability to diffuse through cell membranes and pass into cell interiors. Its chemical properties prevent the formation of damaging ice crystals thus allowing cell storage at or below -180 C. We report here a protocol for successful freezing of small pieces of tissue derived from human brain and human brain tumours. Virtually all specimens could be successfully revived. Assays of phenotype and behaviour show that the cell cultures derived were equivalent to those cultures previously derived from fresh tissue.

  2. Cavernous angioma of brain stem mimicking multiple sclerosis.

    Science.gov (United States)

    Honczarenko, K; Fryze, C; Nowacki, P; Osuch, Z; Grzelec, H; Fabian, A

    1995-01-01

    A 14-year-old boy was admitted to our Department due to peripheral palsy of right VII and bilateral of the VI cranial nerves, spasticity, cerebellar symptoms as well as to dysphagia and dysarthria. In general, he was hospitalized 13 times because of the disease of a relapsing-remitting and next progressive course. He died 31 years after onset of the disease. Multiple sclerosis was diagnosed. Brain autopsy revealed tumor involving almost all brain stem structures and a part of right cerebellar hemisphere. Histologically, cavernous angioma was diagnosed.

  3. Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

    1993-05-01

    Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

  4. Application of contact laser in microsurgery of brain stem tumors

    Directory of Open Access Journals (Sweden)

    Jian-wen GU

    2011-02-01

    Full Text Available Objective To explore the therapeutic efficacy of a new type sapphire contact laser using wavelength-shifting technique on microsurgery of brain stem tumors.Methods The clinical data were retrospectively analyzed of 23 patients(13 males and 10 females,aged 6 to 69 years with an average of 38 years,and the duration of disease was 14 to 36 months with average of 22 months with brain stem tumor admitted from Mar.2006 to May 2010.The major symptoms of the patients were cranial nerve impairment,cerebellum function impairment or paralysis.All patients received microsurgical resection of brain stem tumor using sapphire contact laser through median suboccipital incision and posterior brain stem approach,and the tumors were resected with precision operation and vaporization and ablation.Results Of the 23 patients,4 were with glioma,15 with cavernous angioma,2 with angioreticuloma and 2 with metastatic tumor.Total resection was achieved in 15 cases,while subtotal resection(more than 80% in 6 cases.Intraoperative hemorrhage was less and no intraoperative blood transfusion was required.A 6-months follow-up showed symptoms recovered in 15 patients,improved in 4,unchanged in 2,and worsen in 1.One patient died of recurrence of tumor.No postoperative intracranial infection was occurred,and 2 patients were undergone tracheotomy after operation.The average hospital stay was 15d.Conclusion The contact laser can precisely dissect and vaporize the tumors,increase the resection rate,reduce intraoperative hemorrhage and accessory injuries,and has a clear and definite effect.

  5. Brain dynamics in the auditory Go/NoGo task as a function of EEG frequency.

    Science.gov (United States)

    Barry, Robert J; De Blasio, Frances; Rushby, Jacqueline A; Clarke, Adam R

    2010-11-01

    We examined relationships between the phase of narrow-band electroencephalographic (EEG) activity at stimulus onset and the resultant event-related potentials (ERPs) in an equiprobable auditory Go/NoGo task with a fixed SOA, in the context of a novel conceptualisation of orthogonal phase effects (cortical negativity vs. positivity, negative driving vs. positive driving, waxing vs. waning). ERP responses to each stimulus type were analysed. Prestimulus narrow-band EEG activity (in 1Hz bands from 1 to 13Hz) at Cz was assessed for each trial using FFT decomposition of the EEG data. For each frequency, the cycle at stimulus onset was used to sort trials into four phases, for which ERPs were derived from the raw EEG activity at 9 central sites. The occurrence of preferred phase-defined brain states was confirmed at a number of frequencies, crossing the traditional frequency bands. As expected, these did not differ between Go and NoGo stimuli. These preferred states were associated with more efficient processing of the stimulus, as reflected in differences in latency and amplitude of the N1 and P3 ERP components. The present results, although derived in a different paradigm by EEG decomposition methods different from those used previously, confirm the existence of preferred brain states and their impact on the efficiency of brain dynamics involved in perceptual and cognitive processing. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Brain substrates underlying auditory speech priming in healthy listeners and listeners with schizophrenia.

    Science.gov (United States)

    Wu, C; Zheng, Y; Li, J; Wu, H; She, S; Liu, S; Ning, Y; Li, L

    2017-04-01

    Under 'cocktail party' listening conditions, healthy listeners and listeners with schizophrenia can use temporally pre-presented auditory speech-priming (ASP) stimuli to improve target-speech recognition, even though listeners with schizophrenia are more vulnerable to informational speech masking. Using functional magnetic resonance imaging, this study searched for both brain substrates underlying the unmasking effect of ASP in 16 healthy controls and 22 patients with schizophrenia, and brain substrates underlying schizophrenia-related speech-recognition deficits under speech-masking conditions. In both controls and patients, introducing the ASP condition (against the auditory non-speech-priming condition) not only activated the left superior temporal gyrus (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced functional connectivity of the left STG/pMTG with the left caudate. It also enhanced functional connectivity of the left STG/pMTG with the left pars triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the left Rolandic operculum in patients. The strength of functional connectivity between the left STG and left TriIFG was correlated with target-speech recognition under the speech-masking condition in both controls and patients, but reduced in patients. The left STG/pMTG and their ASP-related functional connectivity with both the left caudate and some frontal regions (the left TriIFG in healthy listeners and the left Rolandic operculum in listeners with schizophrenia) are involved in the unmasking effect of ASP, possibly through facilitating the following processes: masker-signal inhibition, target-speech encoding, and speech production. The schizophrenia-related reduction of functional connectivity between the left STG and left TriIFG augments the vulnerability of speech recognition to speech masking.

  7. Stem cells and cell lines from the human auditory organ: applications, hurdles and bottlenecks in the development of regenerative therapies for deafness.

    Science.gov (United States)

    Rivolta, Marcelo N

    2010-04-01

    The development of any stem-cell-based therapy (and a potential one for deafness is no exception) relies on the generation of the necessary tools: 'cell drugs' that can be safely manufactured for their clinical application. An increasing body of work has focussed on the identification, in animal models, of potential stem cell sources that could have an application for regenerative therapy in the auditory organ. A still more circumscribed effort--owing to ethical and technical difficulties--aims to obtain the actual potential therapeutic candidates (i.e. stem cells of human origin). A recently isolated population of human fetal auditory stem cells could become an ideal model for some of the challenges lying ahead regarding cochlear stem cell purification, expansion and maintenance. 2010 Elsevier Ltd. All rights reserved.

  8. Copine1 regulates neural stem cell functions during brain development.

    Science.gov (United States)

    Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

    2018-01-01

    Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The musical centers of the brain: Vladimir E. Larionov (1857-1929) and the functional neuroanatomy of auditory perception.

    Science.gov (United States)

    Triarhou, Lazaros C; Verina, Tatyana

    2016-11-01

    In 1899 a landmark paper entitled "On the musical centers of the brain" was published in Pflügers Archiv, based on work carried out in the Anatomo-Physiological Laboratory of the Neuropsychiatric Clinic of Vladimir M. Bekhterev (1857-1927) in St. Petersburg, Imperial Russia. The author of that paper was Vladimir E. Larionov (1857-1929), a military doctor and devoted brain scientist, who pursued the problem of the localization of function in the canine and human auditory cortex. His data detailed the existence of tonotopy in the temporal lobe and further demonstrated centrifugal auditory pathways emanating from the auditory cortex and directed to the opposite hemisphere and lower brain centers. Larionov's discoveries have been largely considered as findings of the Bekhterev school. Perhaps this is why there are limited resources on Larionov, especially keeping in mind his military medical career and the fact that after 1917 he just seems to have practiced otorhinolaryngology in Odessa. Larionov died two years after Bekhterev's mysterious death of 1927. The present study highlights the pioneering contributions of Larionov to auditory neuroscience, trusting that the life and work of Vladimir Efimovich will finally, and deservedly, emerge from the shadow of his celebrated master, Vladimir Mikhailovich. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Attention effects on auditory scene analysis: insights from event-related brain potentials.

    Science.gov (United States)

    Spielmann, Mona Isabel; Schröger, Erich; Kotz, Sonja A; Bendixen, Alexandra

    2014-01-01

    Sounds emitted by different sources arrive at our ears as a mixture that must be disentangled before meaningful information can be retrieved. It is still a matter of debate whether this decomposition happens automatically or requires the listener's attention. These opposite positions partly stem from different methodological approaches to the problem. We propose an integrative approach that combines the logic of previous measurements targeting either auditory stream segregation (interpreting a mixture as coming from two separate sources) or integration (interpreting a mixture as originating from only one source). By means of combined behavioral and event-related potential (ERP) measures, our paradigm has the potential to measure stream segregation and integration at the same time, providing the opportunity to obtain positive evidence of either one. This reduces the reliance on zero findings (i.e., the occurrence of stream integration in a given condition can be demonstrated directly, rather than indirectly based on the absence of empirical evidence for stream segregation, and vice versa). With this two-way approach, we systematically manipulate attention devoted to the auditory stimuli (by varying their task relevance) and to their underlying structure (by delivering perceptual tasks that require segregated or integrated percepts). ERP results based on the mismatch negativity (MMN) show no evidence for a modulation of stream integration by attention, while stream segregation results were less clear due to overlapping attention-related components in the MMN latency range. We suggest future studies combining the proposed two-way approach with some improvements in the ERP measurement of sequential stream segregation.

  11. Training leads to increased auditory brain-computer interface performance of end-users with motor impairments.

    Science.gov (United States)

    Halder, S; Käthner, I; Kübler, A

    2016-02-01

    Auditory brain-computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain-computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. Five end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain-computer interface paradigm with natural sounds and directional cues. Three of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17 bits/min) to the last session (3.08 bits/min). The two best end-users achieved information transfer rates of 5.78 bits/min and accuracies of 92%. Our results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. To our knowledge, this is the first time end-users with motor impairments controlled an auditory brain-computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Proteome rearrangements after auditory learning: high-resolution profiling of synapse-enriched protein fractions from mouse brain.

    Science.gov (United States)

    Kähne, Thilo; Richter, Sandra; Kolodziej, Angela; Smalla, Karl-Heinz; Pielot, Rainer; Engler, Alexander; Ohl, Frank W; Dieterich, Daniela C; Seidenbecher, Constanze; Tischmeyer, Wolfgang; Naumann, Michael; Gundelfinger, Eckart D

    2016-07-01

    Learning and memory processes are accompanied by rearrangements of synaptic protein networks. While various studies have demonstrated the regulation of individual synaptic proteins during these processes, much less is known about the complex regulation of synaptic proteomes. Recently, we reported that auditory discrimination learning in mice is associated with a relative down-regulation of proteins involved in the structural organization of synapses in various brain regions. Aiming at the identification of biological processes and signaling pathways involved in auditory memory formation, here, a label-free quantification approach was utilized to identify regulated synaptic junctional proteins and phosphoproteins in the auditory cortex, frontal cortex, hippocampus, and striatum of mice 24 h after the learning experiment. Twenty proteins, including postsynaptic scaffolds, actin-remodeling proteins, and RNA-binding proteins, were regulated in at least three brain regions pointing to common, cross-regional mechanisms. Most of the detected synaptic proteome changes were, however, restricted to individual brain regions. For example, several members of the Septin family of cytoskeletal proteins were up-regulated only in the hippocampus, while Septin-9 was down-regulated in the hippocampus, the frontal cortex, and the striatum. Meta analyses utilizing several databases were employed to identify underlying cellular functions and biological pathways. Data are available via ProteomeExchange with identifier PXD003089. How does the protein composition of synapses change in different brain areas upon auditory learning? We unravel discrete proteome changes in mouse auditory cortex, frontal cortex, hippocampus, and striatum functionally implicated in the learning process. We identify not only common but also area-specific biological pathways and cellular processes modulated 24 h after training, indicating individual contributions of the regions to memory processing. © 2016 The

  13. High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep.

    Science.gov (United States)

    Lustenberger, Caroline; Patel, Yogi A; Alagapan, Sankaraleengam; Page, Jessica M; Price, Betsy; Boyle, Michael R; Fröhlich, Flavio

    2017-12-06

    Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  15. Entracking as a Brain Stem Code for Pitch: The Butte Hypothesis.

    Science.gov (United States)

    Joris, Philip X

    2016-01-01

    The basic nature of pitch is much debated. A robust code for pitch exists in the auditory nerve in the form of an across-fiber pooled interspike interval (ISI) distribution, which resembles the stimulus autocorrelation. An unsolved question is how this representation can be "read out" by the brain. A new view is proposed in which a known brain-stem property plays a key role in the coding of periodicity, which I refer to as "entracking", a contraction of "entrained phase-locking". It is proposed that a scalar rather than vector code of periodicity exists by virtue of coincidence detectors that code the dominant ISI directly into spike rate through entracking. Perfect entracking means that a neuron fires one spike per stimulus-waveform repetition period, so that firing rate equals the repetition frequency. Key properties are invariance with SPL and generalization across stimuli. The main limitation in this code is the upper limit of firing (~ 500 Hz). It is proposed that entracking provides a periodicity tag which is superimposed on a tonotopic analysis: at low SPLs and fundamental frequencies > 500 Hz, a spectral or place mechanism codes for pitch. With increasing SPL the place code degrades but entracking improves and first occurs in neurons with low thresholds for the spectral components present. The prediction is that populations of entracking neurons, extended across characteristic frequency, form plateaus ("buttes") of firing rate tied to periodicity.

  16. An online brain-computer interface based on shifting attention to concurrent streams of auditory stimuli

    Science.gov (United States)

    Hill, N. J.; Schölkopf, B.

    2012-04-01

    We report on the development and online testing of an electroencephalogram-based brain-computer interface (BCI) that aims to be usable by completely paralysed users—for whom visual or motor-system-based BCIs may not be suitable, and among whom reports of successful BCI use have so far been very rare. The current approach exploits covert shifts of attention to auditory stimuli in a dichotic-listening stimulus design. To compare the efficacy of event-related potentials (ERPs) and steady-state auditory evoked potentials (SSAEPs), the stimuli were designed such that they elicited both ERPs and SSAEPs simultaneously. Trial-by-trial feedback was provided online, based on subjects' modulation of N1 and P3 ERP components measured during single 5 s stimulation intervals. All 13 healthy subjects were able to use the BCI, with performance in a binary left/right choice task ranging from 75% to 96% correct across subjects (mean 85%). BCI classification was based on the contrast between stimuli in the attended stream and stimuli in the unattended stream, making use of every stimulus, rather than contrasting frequent standard and rare ‘oddball’ stimuli. SSAEPs were assessed offline: for all subjects, spectral components at the two exactly known modulation frequencies allowed discrimination of pre-stimulus from stimulus intervals, and of left-only stimuli from right-only stimuli when one side of the dichotic stimulus pair was muted. However, attention modulation of SSAEPs was not sufficient for single-trial BCI communication, even when the subject's attention was clearly focused well enough to allow classification of the same trials via ERPs. ERPs clearly provided a superior basis for BCI. The ERP results are a promising step towards the development of a simple-to-use, reliable yes/no communication system for users in the most severely paralysed states, as well as potential attention-monitoring and -training applications outside the context of assistive technology.

  17. An online brain-computer interface based on shifting attention to concurrent streams of auditory stimuli.

    Science.gov (United States)

    Hill, N J; Schölkopf, B

    2012-04-01

    We report on the development and online testing of an electroencephalogram-based brain-computer interface (BCI) that aims to be usable by completely paralysed users-for whom visual or motor-system-based BCIs may not be suitable, and among whom reports of successful BCI use have so far been very rare. The current approach exploits covert shifts of attention to auditory stimuli in a dichotic-listening stimulus design. To compare the efficacy of event-related potentials (ERPs) and steady-state auditory evoked potentials (SSAEPs), the stimuli were designed such that they elicited both ERPs and SSAEPs simultaneously. Trial-by-trial feedback was provided online, based on subjects' modulation of N1 and P3 ERP components measured during single 5 s stimulation intervals. All 13 healthy subjects were able to use the BCI, with performance in a binary left/right choice task ranging from 75% to 96% correct across subjects (mean 85%). BCI classification was based on the contrast between stimuli in the attended stream and stimuli in the unattended stream, making use of every stimulus, rather than contrasting frequent standard and rare 'oddball' stimuli. SSAEPs were assessed offline: for all subjects, spectral components at the two exactly known modulation frequencies allowed discrimination of pre-stimulus from stimulus intervals, and of left-only stimuli from right-only stimuli when one side of the dichotic stimulus pair was muted. However, attention modulation of SSAEPs was not sufficient for single-trial BCI communication, even when the subject's attention was clearly focused well enough to allow classification of the same trials via ERPs. ERPs clearly provided a superior basis for BCI. The ERP results are a promising step towards the development of a simple-to-use, reliable yes/no communication system for users in the most severely paralysed states, as well as potential attention-monitoring and -training applications outside the context of assistive technology.

  18. A case of generalized auditory agnosia with unilateral subcortical brain lesion.

    Science.gov (United States)

    Suh, Hyee; Shin, Yong-Il; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-12-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.

  19. Implications of aneuploidy for stem cell biology and brain therapeutics

    Directory of Open Access Journals (Sweden)

    Sylvie eDevalle

    2012-09-01

    Full Text Available Understanding the cellular basis of neurological disorders have advanced at a slow pace, especially due to the extreme invasiveness of brain biopsying and limitations of cell lines and animal models that have been used. Since the derivation of pluripotent stem cells (PSCs, a novel source of cells for regenerative medicine and disease modeling has become available, holding great potential for the neurology field. However, safety for therapy and accurateness for modeling have been a matter of intense debate, considering that genomic instability, including the gain and loss of chromosomes (aneuploidy, has been repeatedly observed in those cells. Despite the fact that recent reports have described some degree of aneuploidy as being normal during neuronal differentiation and present in healthy human brains, this phenomenon is particularly controversial since it has traditionally been associated with cancer and disabling syndromes. It is therefore necessary to appreciate, to which extent, aneuploid pluripotent stem cells are suitable for regenerative medicine and neurological modeling and also the limits that separate constitutive from disease-related aneuploidy. In this review, recent findings regarding chromosomal instability in PSCs and within the brain will be discussed.

  20. Behavioral and brain pattern differences between acting and observing in an auditory task

    Directory of Open Access Journals (Sweden)

    Ventouras Errikos M

    2009-01-01

    Full Text Available Abstract Background Recent research has shown that errors seem to influence the patterns of brain activity. Additionally current notions support the idea that similar brain mechanisms are activated during acting and observing. The aim of the present study was to examine the patterns of brain activity of actors and observers elicited upon receiving feedback information of the actor's response. Methods The task used in the present research was an auditory identification task that included both acting and observing settings, ensuring concurrent ERP measurements of both participants. The performance of the participants was investigated in conditions of varying complexity. ERP data were analyzed with regards to the conditions of acting and observing in conjunction to correct and erroneous responses. Results The obtained results showed that the complexity induced by cue dissimilarity between trials was a demodulating factor leading to poorer performance. The electrophysiological results suggest that feedback information results in different intensities of the ERP patterns of observers and actors depending on whether the actor had made an error or not. The LORETA source localization method yielded significantly larger electrical activity in the supplementary motor area (Brodmann area 6, the posterior cingulate gyrus (Brodmann area 31/23 and the parietal lobe (Precuneus/Brodmann area 7/5. Conclusion These findings suggest that feedback information has a different effect on the intensities of the ERP patterns of actors and observers depending on whether the actor committed an error. Certain neural systems, including medial frontal area, posterior cingulate gyrus and precuneus may mediate these modulating effects. Further research is needed to elucidate in more detail the neuroanatomical and neuropsychological substrates of these systems.

  1. Effects of auditory stimuli on electrical activity in the brain during cycle ergometry.

    Science.gov (United States)

    Bigliassi, Marcelo; Karageorghis, Costas I; Wright, Michael J; Orgs, Guido; Nowicky, Alexander V

    2017-08-01

    The present study sought to further understanding of the brain mechanisms that underlie the effects of music on perceptual, affective, and visceral responses during whole-body modes of exercise. Eighteen participants were administered light-to-moderate intensity bouts of cycle ergometer exercise. Each exercise bout was of 12-min duration (warm-up [3min], exercise [6min], and warm-down [3min]). Portable techniques were used to monitor the electrical activity in the brain, heart, and muscle during the administration of three conditions: music, audiobook, and control. Conditions were randomized and counterbalanced to prevent any influence of systematic order on the dependent variables. Oscillatory potentials at the Cz electrode site were used to further understanding of time-frequency changes influenced by voluntary control of movements. Spectral coherence analysis between Cz and frontal, frontal-central, central, central-parietal, and parietal electrode sites was also calculated. Perceptual and affective measures were taken at five timepoints during the exercise bout. Results indicated that music reallocated participants' attentional focus toward auditory pathways and reduced perceived exertion. The music also inhibited alpha resynchronization at the Cz electrode site and reduced the spectral coherence values at Cz-C4 and Cz-Fz. The reduced focal awareness induced by music led to a more autonomous control of cycle movements performed at light-to-moderate-intensities. Processing of interoceptive sensory cues appears to upmodulate fatigue-related sensations, increase the connectivity in the frontal and central regions of the brain, and is associated with neural resynchronization to sustain the imposed exercise intensity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Auditory Hallucinations in Acute Stroke

    Directory of Open Access Journals (Sweden)

    Yair Lampl

    2005-01-01

    Full Text Available Auditory hallucinations are uncommon phenomena which can be directly caused by acute stroke, mostly described after lesions of the brain stem, very rarely reported after cortical strokes. The purpose of this study is to determine the frequency of this phenomenon. In a cross sectional study, 641 stroke patients were followed in the period between 1996–2000. Each patient underwent comprehensive investigation and follow-up. Four patients were found to have post cortical stroke auditory hallucinations. All of them occurred after an ischemic lesion of the right temporal lobe. After no more than four months, all patients were symptom-free and without therapy. The fact the auditory hallucinations may be of cortical origin must be taken into consideration in the treatment of stroke patients. The phenomenon may be completely reversible after a couple of months.

  3. Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor.

    Science.gov (United States)

    Jayakar, Reema; King, Tricia Z; Morris, Robin; Na, Sabrina

    2015-03-01

    We examined the nature of verbal memory deficits and the possible hippocampal underpinnings in long-term adult survivors of childhood brain tumor. 35 survivors (M = 24.10 ± 4.93 years at testing; 54% female), on average 15 years post-diagnosis, and 59 typically developing adults (M = 22.40 ± 4.35 years, 54% female) participated. Automated FMRIB Software Library (FSL) tools were used to measure hippocampal, putamen, and whole brain volumes. The California Verbal Learning Test-Second Edition (CVLT-II) was used to assess verbal memory. Hippocampal, F(1, 91) = 4.06, ηp² = .04; putamen, F(1, 91) = 11.18, ηp² = .11; and whole brain, F(1, 92) = 18.51, ηp² = .17, volumes were significantly lower for survivors than controls (p memory indices of auditory attention list span (Trial 1: F(1, 92) = 12.70, η² = .12) and final list learning (Trial 5: F(1, 92) = 6.01, η² = .06) were significantly lower for survivors (p Memory differences between survivors and controls are largely contingent upon auditory attention list span. Only hippocampal volume is associated with the auditory attention list span component of verbal memory. These findings are particularly robust for survivors treated with radiation. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  4. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course

    OpenAIRE

    Schaefer, Jennifer E.

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis ...

  5. Communication and control by listening: towards optimal design of a two-class auditory streaming brain-computer interface

    Directory of Open Access Journals (Sweden)

    N. Jeremy Hill

    2012-12-01

    Full Text Available Most brain-computer interface (BCI systems require users to modulate brain signals in response to visual stimuli. Thus, they may not be useful to people with limited vision, such as those with severe paralysis. One important approach for overcoming this issue is auditory streaming, an approach whereby a BCI system is driven by shifts of attention between two dichotically presented auditory stimulus streams. Motivated by the long-term goal of translating such a system into a reliable, simple yes-no interface for clinical usage, we aim to answer two main questions. First, we asked which of two previously-published variants provides superior performance: a fixed-phase (FP design in which the streams have equal period and opposite phase, or a drifting-phase (DP design where the periods are unequal. We found FP to be superior to DP (p = 0.002: average performance levels were 80% and 72% correct, respectively. We were also able to show, in a pilot with one subject, that auditory streaming can support continuous control and neurofeedback applications: by shifting attention between ongoing left and right auditory streams, the subject was able to control the position of a paddle in a computer game. Second, we examined whether the system is dependent on eye movements, since it is known that eye movements and auditory attention may influence each other, and any dependence on the ability to move one’s eyes would be a barrier to translation to paralyzed users. We discovered that, despite instructions, some subjects did make eye movements that were indicative of the direction of attention. However, there was no correlation, across subjects, between the reliability of the eye movement signal and the reliability of the BCI system, indicating that our system was configured to work independently of eye movement. Together, these findings are an encouraging step forward toward BCIs that provide practical communication and control options for the most severely

  6. Non-invasive Brain Stimulation and Auditory Verbal Hallucinations: New Techniques and Future Directions.

    Science.gov (United States)

    Moseley, Peter; Alderson-Day, Ben; Ellison, Amanda; Jardri, Renaud; Fernyhough, Charles

    2015-01-01

    Auditory verbal hallucinations (AVHs) are the experience of hearing a voice in the absence of any speaker. Results from recent attempts to treat AVHs with neurostimulation (rTMS or tDCS) to the left temporoparietal junction have not been conclusive, but suggest that it may be a promising treatment option for some individuals. Some evidence suggests that the therapeutic effect of neurostimulation on AVHs may result from modulation of cortical areas involved in the ability to monitor the source of self-generated information. Here, we provide a brief overview of cognitive models and neurostimulation paradigms associated with treatment of AVHs, and discuss techniques that could be explored in the future to improve the efficacy of treatment, including alternating current and random noise stimulation. Technical issues surrounding the use of neurostimulation as a treatment option are discussed (including methods to localize the targeted cortical area, and the state-dependent effects of brain stimulation), as are issues surrounding the acceptability of neurostimulation for adolescent populations and individuals who experience qualitatively different types of AVH.

  7. Noninvasive brain stimulation and auditory verbal hallucinations: new techniques and future directions

    Directory of Open Access Journals (Sweden)

    Peter eMoseley

    2016-01-01

    Full Text Available Auditory verbal hallucinations (AVHs are the experience of hearing a voice in the absence of any speaker. Results from recent attempts to treat AVHs with neurostimulation (rTMS or tDCS to the left temporoparietal junction have not been conclusive, but suggest that it may be a promising treatment option for some individuals. Some evidence suggests that the therapeutic effect of neurostimulation on AVHs may result from modulation of cortical areas involved in the ability to monitor the source of self-generated information. Here, we provide a brief overview of cognitive models and neurostimulation paradigms associated with treatment of AVHs, and discuss techniques that could be explored in the future to improve the efficacy of treatment, including alternating current and random noise stimulation. Technical issues surrounding the use of neurostimulation as a treatment option are discussed (including methods to localise the targeted cortical area, and the state-dependent effects of brain stimulation, as are issues surrounding the acceptability of neurostimulation for adolescent populations and individuals who experience qualitatively different types of AVH.

  8. Risk of depression enhances auditory Pitch discrimination in the brain as indexed by the mismatch negativity.

    Science.gov (United States)

    Bonetti, L; Haumann, N T; Vuust, P; Kliuchko, M; Brattico, E

    2017-10-01

    Depression is a state of aversion to activity and low mood that affects behaviour, thoughts, feelings and sense of well-being. Moreover, the individual depression trait is associated with altered auditory cortex activation and appraisal of the affective content of sounds. Mismatch negativity responses (MMNs) to acoustic feature changes (pitch, timbre, location, intensity, slide and rhythm) inserted in a musical sequence played in major or minor mode were recorded using magnetoencephalography (MEG) in 88 subclinical participants with depression risk. We found correlations between MMNs to slide and pitch and the level of depression risk reported by participants, indicating that higher MMNs correspond to higher risk of depression. Furthermore we found significantly higher MMN amplitudes to mistuned pitches within a major context compared to MMNs to pitch changes in a minor context. The brains of individuals with depression risk are more responsive to mistuned and fast pitch stimulus changes, even at a pre-attentive level. Considering the altered appraisal of affective contents of sounds in depression and the relevance of spectral pitch features for those contents in music and speech, we propose that individuals with subclinical depression risk are more tuned to tracking sudden pitch changes. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  9. Rhythmic Auditory Stimulation in Gait Training for Patients with Traumatic Brain Injury.

    Science.gov (United States)

    Hurt; Rice; McIntosh; Thaut

    1998-01-01

    Rhythmic auditory stimulation (RAS) was studied in a frequency entrainment design and as a therapeutic stimulus to facilitate gait patterns in 8 traumatically brain injured individuals (5 male/3 female; mean age 30 +/- 5 years) with persisting gait disorder, 4-24 months postinjury. During entrainment, with RAS frequency matched to baseline cadence, velocity and stride symmetry both increased by an average of 18%. Increases contributing to the velocity improvement were seen in both stride length (7%) and cadence (8%). With RAS accelerated 5% over the fast walking step rate of the patients, 5 patients could entrain to a higher step frequency. The 2 patients with the slowest baseline gait velocity could not entrain to faster RAS frequencies. After 5 weeks of daily RAS training, 5 patients' mean velocity increased significantly (p

  10. Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease.

    Science.gov (United States)

    Moradi, Elaheh; Hallikainen, Ilona; Hänninen, Tuomo; Tohka, Jussi

    2017-01-01

    Rey's Auditory Verbal Learning Test (RAVLT) is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD), thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting) and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI) data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50) and RAVLT Percent Forgetting (R = 0.43) in a dataset consisting of 806 AD, mild cognitive impairment (MCI) or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.

  11. Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Elaheh Moradi

    2017-01-01

    Full Text Available Rey's Auditory Verbal Learning Test (RAVLT is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD, thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50 and RAVLT Percent Forgetting (R = 0.43 in a dataset consisting of 806 AD, mild cognitive impairment (MCI or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.

  12. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

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    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  13. Anatomy, Physiology and Function of the Auditory System

    Science.gov (United States)

    Kollmeier, Birger

    The human ear consists of the outer ear (pinna or concha, outer ear canal, tympanic membrane), the middle ear (middle ear cavity with the three ossicles malleus, incus and stapes) and the inner ear (cochlea which is connected to the three semicircular canals by the vestibule, which provides the sense of balance). The cochlea is connected to the brain stem via the eighth brain nerve, i.e. the vestibular cochlear nerve or nervus statoacusticus. Subsequently, the acoustical information is processed by the brain at various levels of the auditory system. An overview about the anatomy of the auditory system is provided by Figure 1.

  14. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

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    Mikkel Wallentin

    2016-01-01

    Full Text Available Klinefelter syndrome (47, XXY (KS is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS = 49; Controls = 49 responded to whether the words “GREEN” or “RED” were displayed in green or red (incongruent versus congruent colors. One of the colors was presented three times as often as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying “GREEN” or “RED” had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased response to motor output in primary motor cortex and an increased response to auditory stimuli in auditory cortices, but no difference in primary visual cortices. KS displayed a diminished response to written visual stimuli in secondary visual regions near the Visual Word Form Area, consistent with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain's motor network with no difference between groups. No effects of testosterone level or brain volume were found. In sum, the present findings suggest that auditory and motor systems in KS are selectively affected, perhaps as a compensatory strategy, and that this is not a systemic effect as it is not seen in the visual system.

  15. An evaluation of training with an auditory P300 brain-computer interface for the Japanese Hiragana syllabary

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    Sebastian Halder

    2016-09-01

    Full Text Available Gaze-independent brain-computer interfaces (BCIs are a possible communication channel for persons with paralysis. We investigated if it is possible to use auditory stimuli to create a BCI for the Japanese Hiragana syllabary, which has 46 Hiragana characters. Additionally, we investigated if training has an effect on accuracy despite the high amount of different stimuli involved. Able-bodied participants (N=6 were asked to select 25 syllables (out of fifty possible choices using a two step procedure: first the consonant (ten choices and then the vowel (five choices. This was repeated on three separate days. Additionally, a person with spinal cord injury (SCI participated in the experiment. Four out of six healthy participants reached Hiragana syllable accuracies above 70% and the information transfer rate increased from 1.7 bits/min in the first session to 3.2 bits/min in the third session. The accuracy of the participant with SCI increased from 12% (0.2 bits/min to 56% (2 bits/min in session three. Reliable selections from a 10×5 matrix using auditory stimuli were possible and performance is increased by training. We were able to show that auditory P300 BCIs can be used for communication with up to fifty symbols. This enables the use of the technology of auditory P300 BCIs with a variety of applications.

  16. Cortical Auditory Disorders: A Case of Non-Verbal Disturbances Assessed with Event-Related Brain Potentials

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    Sönke Johannes

    1998-01-01

    Full Text Available In the auditory modality, there has been a considerable debate about some aspects of cortical disorders, especially about auditory forms of agnosia. Agnosia refers to an impaired comprehension of sensory information in the absence of deficits in primary sensory processes. In the non-verbal domain, sound agnosia and amusia have been reported but are frequently accompanied by language deficits whereas pure deficits are rare. Absolute pitch and musicians’ musical abilities have been associated with left hemispheric functions. We report the case of a right handed sound engineer with the absolute pitch who developed sound agnosia and amusia in the absence of verbal deficits after a right perisylvian stroke. His disabilities were assessed with the Seashore Test of Musical Functions, the tests of Wertheim and Botez (Wertheim and Botez, Brain 84, 1961, 19–30 and by event-related potentials (ERP recorded in a modified 'oddball paradigm’. Auditory ERP revealed a dissociation between the amplitudes of the P3a and P3b subcomponents with the P3b being reduced in amplitude while the P3a was undisturbed. This is interpreted as reflecting disturbances in target detection processes as indexed by the P3b. The findings that contradict some aspects of current knowledge about left/right hemispheric specialization in musical processing are discussed and related to the literature concerning cortical auditory disorders.

  17. Brain-computer interfaces using capacitive measurement of visual or auditory steady-state responses.

    Science.gov (United States)

    Baek, Hyun Jae; Kim, Hyun Seok; Heo, Jeong; Lim, Yong Gyu; Park, Kwang Suk

    2013-04-01

    Brain-computer interface (BCI) technologies have been intensely studied to provide alternative communication tools entirely independent of neuromuscular activities. Current BCI technologies use electroencephalogram (EEG) acquisition methods that require unpleasant gel injections, impractical preparations and clean-up procedures. The next generation of BCI technologies requires practical, user-friendly, nonintrusive EEG platforms in order to facilitate the application of laboratory work in real-world settings. A capacitive electrode that does not require an electrolytic gel or direct electrode-scalp contact is a potential alternative to the conventional wet electrode in future BCI systems. We have proposed a new capacitive EEG electrode that contains a conductive polymer-sensing surface, which enhances electrode performance. This paper presents results from five subjects who exhibited visual or auditory steady-state responses according to BCI using these new capacitive electrodes. The steady-state visual evoked potential (SSVEP) spelling system and the auditory steady-state response (ASSR) binary decision system were employed. Offline tests demonstrated BCI performance high enough to be used in a BCI system (accuracy: 95.2%, ITR: 19.91 bpm for SSVEP BCI (6 s), accuracy: 82.6%, ITR: 1.48 bpm for ASSR BCI (14 s)) with the analysis time being slightly longer than that when wet electrodes were employed with the same BCI system (accuracy: 91.2%, ITR: 25.79 bpm for SSVEP BCI (4 s), accuracy: 81.3%, ITR: 1.57 bpm for ASSR BCI (12 s)). Subjects performed online BCI under the SSVEP paradigm in copy spelling mode and under the ASSR paradigm in selective attention mode with a mean information transfer rate (ITR) of 17.78 ± 2.08 and 0.7 ± 0.24 bpm, respectively. The results of these experiments demonstrate the feasibility of using our capacitive EEG electrode in BCI systems. This capacitive electrode may become a flexible and non-intrusive tool fit for various applications in

  18. A case of a brain stem abscess with a favorable outcome

    NARCIS (Netherlands)

    Bulthuis, Vincent J; Gubler, Felix S; Teernstra, Onno P M; Temel, Yasin

    2015-01-01

    BACKGROUND: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. CASE DESCRIPTION: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed

  19. Repetition suppression and repetition enhancement underlie auditory memory-trace formation in the human brain: an MEG study.

    Science.gov (United States)

    Recasens, Marc; Leung, Sumie; Grimm, Sabine; Nowak, Rafal; Escera, Carles

    2015-03-01

    The formation of echoic memory traces has traditionally been inferred from the enhanced responses to its deviations. The mismatch negativity (MMN), an auditory event-related potential (ERP) elicited between 100 and 250ms after sound deviation is an indirect index of regularity encoding that reflects a memory-based comparison process. Recently, repetition positivity (RP) has been described as a candidate ERP correlate of direct memory trace formation. RP consists of repetition suppression and enhancement effects occurring in different auditory components between 50 and 250ms after sound onset. However, the neuronal generators engaged in the encoding of repeated stimulus features have received little interest. This study intends to investigate the neuronal sources underlying the formation and strengthening of new memory traces by employing a roving-standard paradigm, where trains of different frequencies and different lengths are presented randomly. Source generators of repetition enhanced (RE) and suppressed (RS) activity were modeled using magnetoencephalography (MEG) in healthy subjects. Our results show that, in line with RP findings, N1m (~95-150ms) activity is suppressed with stimulus repetition. In addition, we observed the emergence of a sustained field (~230-270ms) that showed RE. Source analysis revealed neuronal generators of RS and RE located in both auditory and non-auditory areas, like the medial parietal cortex and frontal areas. The different timing and location of neural generators involved in RS and RE points to the existence of functionally separated mechanisms devoted to acoustic memory-trace formation in different auditory processing stages of the human brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Intranasal dexmedetomidine: an effective sedative agent for electroencephalogram and auditory brain response testing.

    Science.gov (United States)

    Baier, Nicole M; Mendez, Suzanne S; Kimm, Danielle; Velazquez, Amanda E; Schroeder, Alan R

    2016-03-01

    Dexmedetomidine is an α2 agonist with sedative, anxiolytic, and analgesic properties. The intranasal (IN) route avoids the pain of intravenous (i.v.) catheter placement but limited literature exists on the use of IN dexmedetomidine. This study examines the effectiveness and safety of IN dexmedetomidine for sedation of patients undergoing electroencephalogram (EEG) and auditory brain response (ABR) testing. This was a review of all outpatients sedated with IN dexmedetomidine for EEG or ABR between October 1, 2012 and October 1, 2014. An initial dose of 2.5-3 μg · kg(-1) IN dexmedetomidine was given with a repeat dose of 1-1.5 μg · kg(-1) IN if needed 30 min later. Prospectively entered patient information was extracted from a quality assurance database and additional information gathered via retrospective chart review. Intranasal dexmedetomidine was used in 169 patients (EEG = 117, ABR = 52). First-dose success rates were 90.4% for ABR and 87.2% for EEG. Total success rates (with one or two doses of IN dexmedetomidine) were 100% for ABR and 99.1% for EEG. The median time to onset of sleep was 25 min (IQR, 20-32 min). The median duration of sedation was 107 min (IQR, 90-131 min). Adverse events included: 18 patients (10.7%) with hypotension which resolved without intervention, six patients with oxygen desaturation <90%, two of whom received supplemental oxygen, and one patient with an underlying upper airway abnormality who was treated with continuous positive airway pressure. IN dexmedetomidine is an effective and noninvasive method of sedating children for EEG and ABR. © 2016 John Wiley & Sons Ltd.

  1. A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

    Science.gov (United States)

    2014-10-01

    derived neurons for inner ear therapy : InTech. Hester ME, Murtha MJ, Song S, Rao M, Miranda CJ, Meyer K, Tian J, Boulting G, Schaffer DV, Zhu MX...Department of Defense – Army Award Period: 07/01/11 – 07/31/14 Title: Prevention and Treatment of Noise-Induced Tinnitus Role: Co-Investigator U01...Amount: $140,327 year Title: Combined Auditory-Somatosensory Stimulation to Alleviate Tinnitus Ended Awards: W81XWH-11-1-0414, PI Altschuler, Sponsor

  2. Atypical Bilateral Brain Synchronization in the Early Stage of Human Voice Auditory Processing in Young Children with Autism.

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    Toshiharu Kurita

    Full Text Available Autism spectrum disorder (ASD has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical interhemispheric circuitry. In the context of ASD, alterations in both peripheral and central auditory processes have also attracted a great deal of interest because these changes appear to represent pathophysiological processes; therefore, many prior studies have focused on atypical auditory responses in ASD. The auditory evoked field (AEF, recorded by magnetoencephalography, and the synchronization of these processes between right and left hemispheres was recently suggested to reflect various cognitive abilities in children. However, to date, no previous study has focused on AEF synchronization in ASD subjects. To assess global coordination across spatially distributed brain regions, the analysis of Omega complexity from multichannel neurophysiological data was proposed. Using Omega complexity analysis, we investigated the global coordination of AEFs in 3-8-year-old typically developing (TD children (n = 50 and children with ASD (n = 50 in 50-ms time-windows. Children with ASD displayed significantly higher Omega complexities compared with TD children in the time-window of 0-50 ms, suggesting lower whole brain synchronization in the early stage of the P1m component. When we analyzed the left and right hemispheres separately, no significant differences in any time-windows were observed. These results suggest lower right-left hemispheric synchronization in children with ASD compared with TD children. Our study provides new evidence of aberrant neural synchronization in young children with ASD by investigating auditory evoked neural responses to the human voice.

  3. Progressive multifocal leukoencephalopathy limited to the brain stem

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    Kastrup, O.; Maschke, M.; Diener, H.C. [Neurologische Universitaetsklinik, University of Essen (Germany); Wanke, I. [Department of Neuroradiology, University of Essen (Germany)

    2002-03-01

    Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating slow-virus encephalitis caused by the JC polyomavirus in 2-5% of patients with AIDS. MRI typically shows multiple lesions in the cerebral hemispheres. We present a rare case of rapidly evolving and lethal PML with a severe bulbar syndrome and spastic tetraparesis in a patient with AIDS. MRI showed high-signal lesions on T2-weighted images confined to the brain stem, extending from the medulla oblongata to the midbrain. JC virus polymerase chain reaction in cerebrospinal fluid was positive, and neuropathology showed the findings of PML. This case was also notable because of the rapid progression despite improved immune status with antiretroviral therapy. (orig.)

  4. Plasticity in the neural coding of auditory space in the mammalian brain

    Science.gov (United States)

    King, Andrew J.; Parsons, Carl H.; Moore, David R.

    2000-10-01

    Sound localization relies on the neural processing of monaural and binaural spatial cues that arise from the way sounds interact with the head and external ears. Neurophysiological studies of animals raised with abnormal sensory inputs show that the map of auditory space in the superior colliculus is shaped during development by both auditory and visual experience. An example of this plasticity is provided by monaural occlusion during infancy, which leads to compensatory changes in auditory spatial tuning that tend to preserve the alignment between the neural representations of visual and auditory space. Adaptive changes also take place in sound localization behavior, as demonstrated by the fact that ferrets raised and tested with one ear plugged learn to localize as accurately as control animals. In both cases, these adjustments may involve greater use of monaural spectral cues provided by the other ear. Although plasticity in the auditory space map seems to be restricted to development, adult ferrets show some recovery of sound localization behavior after long-term monaural occlusion. The capacity for behavioral adaptation is, however, task dependent, because auditory spatial acuity and binaural unmasking (a measure of the spatial contribution to the "cocktail party effect") are permanently impaired by chronically plugging one ear, both in infancy but especially in adulthood. Experience-induced plasticity allows the neural circuitry underlying sound localization to be customized to individual characteristics, such as the size and shape of the head and ears, and to compensate for natural conductive hearing losses, including those associated with middle ear disease in infancy.

  5. Active auditory experience in infancy promotes brain plasticity in Theta and Gamma oscillations

    Directory of Open Access Journals (Sweden)

    Gabriella Musacchia

    2017-08-01

    Full Text Available Language acquisition in infants is driven by on-going neural plasticity that is acutely sensitive to environmental acoustic cues. Recent studies showed that attention-based experience with non-linguistic, temporally-modulated auditory stimuli sharpens cortical responses. A previous ERP study from this laboratory showed that interactive auditory experience via behavior-based feedback (AEx, over a 6-week period from 4- to 7-months-of-age, confers a processing advantage, compared to passive auditory exposure (PEx or maturation alone (Naïve Control, NC. Here, we provide a follow-up investigation of the underlying neural oscillatory patterns in these three groups. In AEx infants, Standard stimuli with invariant frequency (STD elicited greater Theta-band (4–6 Hz activity in Right Auditory Cortex (RAC, as compared to NC infants, and Deviant stimuli with rapid frequency change (DEV elicited larger responses in Left Auditory Cortex (LAC. PEx and NC counterparts showed less-mature bilateral patterns. AEx infants also displayed stronger Gamma (33–37 Hz activity in the LAC during DEV discrimination, compared to NCs, while NC and PEx groups demonstrated bilateral activity in this band, if at all. This suggests that interactive acoustic experience with non-linguistic stimuli can promote a distinct, robust and precise cortical pattern during rapid auditory processing, perhaps reflecting mechanisms that support fine-tuning of early acoustic mapping.

  6. Proliferation of differentiated glial cells in the brain stem

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    Barradas P.C.

    1998-01-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  7. Fast learning of simple perceptual discriminations reduces brain activation in working memory and in high-level auditory regions.

    Science.gov (United States)

    Daikhin, Luba; Ahissar, Merav

    2015-07-01

    Introducing simple stimulus regularities facilitates learning of both simple and complex tasks. This facilitation may reflect an implicit change in the strategies used to solve the task when successful predictions regarding incoming stimuli can be formed. We studied the modifications in brain activity associated with fast perceptual learning based on regularity detection. We administered a two-tone frequency discrimination task and measured brain activation (fMRI) under two conditions: with and without a repeated reference tone. Although participants could not explicitly tell the difference between these two conditions, the introduced regularity affected both performance and the pattern of brain activation. The "No-Reference" condition induced a larger activation in frontoparietal areas known to be part of the working memory network. However, only the condition with a reference showed fast learning, which was accompanied by a reduction of activity in two regions: the left intraparietal area, involved in stimulus retention, and the posterior superior-temporal area, involved in representing auditory regularities. We propose that this joint reduction reflects a reduction in the need for online storage of the compared tones. We further suggest that this change reflects an implicit strategic shift "backwards" from reliance mainly on working memory networks in the "No-Reference" condition to increased reliance on detected regularities stored in high-level auditory networks.

  8. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  9. Music and natural sounds in an auditory steady-state response based brain-computer interface to increase user acceptance.

    Science.gov (United States)

    Heo, Jeong; Baek, Hyun Jae; Hong, Seunghyeok; Chang, Min Hye; Lee, Jeong Su; Park, Kwang Suk

    2017-05-01

    Patients with total locked-in syndrome are conscious; however, they cannot express themselves because most of their voluntary muscles are paralyzed, and many of these patients have lost their eyesight. To improve the quality of life of these patients, there is an increasing need for communication-supporting technologies that leverage the remaining senses of the patient along with physiological signals. The auditory steady-state response (ASSR) is an electro-physiologic response to auditory stimulation that is amplitude-modulated by a specific frequency. By leveraging the phenomenon whereby ASSR is modulated by mind concentration, a brain-computer interface paradigm was proposed to classify the selective attention of the patient. In this paper, we propose an auditory stimulation method to minimize auditory stress by replacing the monotone carrier with familiar music and natural sounds for an ergonomic system. Piano and violin instrumentals were employed in the music sessions; the sounds of water streaming and cicadas singing were used in the natural sound sessions. Six healthy subjects participated in the experiment. Electroencephalograms were recorded using four electrodes (Cz, Oz, T7 and T8). Seven sessions were performed using different stimuli. The spectral power at 38 and 42Hz and their ratio for each electrode were extracted as features. Linear discriminant analysis was utilized to classify the selections for each subject. In offline analysis, the average classification accuracies with a modulation index of 1.0 were 89.67% and 87.67% using music and natural sounds, respectively. In online experiments, the average classification accuracies were 88.3% and 80.0% using music and natural sounds, respectively. Using the proposed method, we obtained significantly higher user-acceptance scores, while maintaining a high average classification accuracy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans.

    Science.gov (United States)

    Marks, Kendra L; Martel, David T; Wu, Calvin; Basura, Gregory J; Roberts, Larry E; Schvartz-Leyzac, Kara C; Shore, Susan E

    2018-01-03

    The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus induced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. We delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-inducing bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-inducing bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that induces LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  11. Towards user-friendly spelling with an auditory brain-computer interface: the CharStreamer paradigm.

    Directory of Open Access Journals (Sweden)

    Johannes Höhne

    Full Text Available Realizing the decoding of brain signals into control commands, brain-computer interfaces (BCI aim to establish an alternative communication pathway for locked-in patients. In contrast to most visual BCI approaches which use event-related potentials (ERP of the electroencephalogram, auditory BCI systems are challenged with ERP responses, which are less class-discriminant between attended and unattended stimuli. Furthermore, these auditory approaches have more complex interfaces which imposes a substantial workload on their users. Aiming for a maximally user-friendly spelling interface, this study introduces a novel auditory paradigm: "CharStreamer". The speller can be used with an instruction as simple as "please attend to what you want to spell". The stimuli of CharStreamer comprise 30 spoken sounds of letters and actions. As each of them is represented by the sound of itself and not by an artificial substitute, it can be selected in a one-step procedure. The mental mapping effort (sound stimuli to actions is thus minimized. Usability is further accounted for by an alphabetical stimulus presentation: contrary to random presentation orders, the user can foresee the presentation time of the target letter sound. Healthy, normal hearing users (n = 10 of the CharStreamer paradigm displayed ERP responses that systematically differed between target and non-target sounds. Class-discriminant features, however, varied individually from the typical N1-P2 complex and P3 ERP components found in control conditions with random sequences. To fully exploit the sequential presentation structure of CharStreamer, novel data analysis approaches and classification methods were introduced. The results of online spelling tests showed that a competitive spelling speed can be achieved with CharStreamer. With respect to user rating, it clearly outperforms a control setup with random presentation sequences.

  12. Towards User-Friendly Spelling with an Auditory Brain-Computer Interface: The CharStreamer Paradigm

    Science.gov (United States)

    Höhne, Johannes; Tangermann, Michael

    2014-01-01

    Realizing the decoding of brain signals into control commands, brain-computer interfaces (BCI) aim to establish an alternative communication pathway for locked-in patients. In contrast to most visual BCI approaches which use event-related potentials (ERP) of the electroencephalogram, auditory BCI systems are challenged with ERP responses, which are less class-discriminant between attended and unattended stimuli. Furthermore, these auditory approaches have more complex interfaces which imposes a substantial workload on their users. Aiming for a maximally user-friendly spelling interface, this study introduces a novel auditory paradigm: “CharStreamer”. The speller can be used with an instruction as simple as “please attend to what you want to spell”. The stimuli of CharStreamer comprise 30 spoken sounds of letters and actions. As each of them is represented by the sound of itself and not by an artificial substitute, it can be selected in a one-step procedure. The mental mapping effort (sound stimuli to actions) is thus minimized. Usability is further accounted for by an alphabetical stimulus presentation: contrary to random presentation orders, the user can foresee the presentation time of the target letter sound. Healthy, normal hearing users (n = 10) of the CharStreamer paradigm displayed ERP responses that systematically differed between target and non-target sounds. Class-discriminant features, however, varied individually from the typical N1-P2 complex and P3 ERP components found in control conditions with random sequences. To fully exploit the sequential presentation structure of CharStreamer, novel data analysis approaches and classification methods were introduced. The results of online spelling tests showed that a competitive spelling speed can be achieved with CharStreamer. With respect to user rating, it clearly outperforms a control setup with random presentation sequences. PMID:24886978

  13. Auditory middle latency responses differ in right- and left-handed subjects: an evaluation through topographic brain mapping.

    Science.gov (United States)

    Mohebbi, Mehrnaz; Mahmoudian, Saeid; Alborzi, Marzieh Sharifian; Najafi-Koopaie, Mojtaba; Farahani, Ehsan Darestani; Farhadi, Mohammad

    2014-09-01

    To investigate the association of handedness with auditory middle latency responses (AMLRs) using topographic brain mapping by comparing amplitudes and latencies in frontocentral and hemispheric regions of interest (ROIs). The study included 44 healthy subjects with normal hearing (22 left handed and 22 right handed). AMLRs were recorded from 29 scalp electrodes in response to binaural 4-kHz tone bursts. Frontocentral ROI comparisons revealed that Pa and Pb amplitudes were significantly larger in the left-handed than the right-handed group. Topographic brain maps showed different distributions in AMLR components between the two groups. In hemispheric comparisons, Pa amplitude differed significantly across groups. A left-hemisphere emphasis of Pa was found in the right-handed group but not in the left-handed group. This study provides evidence that handedness is associated with AMLR components in frontocentral and hemispheric ROI. Handedness should be considered an essential factor in the clinical or experimental use of AMLRs.

  14. Wallerian degeneration of the corticospinal tract in the brain stem; MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato (Kyushu Rosai Hospital, Kitakyushu, Fukuoka (Japan))

    1989-04-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T{sub 2}-weighted images - with or without decreased signal intensities in axial T{sub 1}-weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T{sub 1}-weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author).

  15. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

    Science.gov (United States)

    Behnan, Jinan; Isakson, Pauline; Joel, Mrinal; Cilio, Corrado; Langmoen, Iver A; Vik-Mo, Einar O; Badn, Wiaam

    2014-05-01

    The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients. © 2013 AlphaMed Press.

  16. Childhood Brain Stem Glioma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood brain stem glioma presents as a diffuse intrinsic pontine glioma (DIPG; a fast-growing tumor that is difficult to treat and has a poor prognosis) or a focal glioma (grows more slowly, is easier to treat, and has a better prognosis). Learn about the diagnosis, cellular classification, staging, treatment, and clinical trials for pediatric brain stem glioma in this expert-reviewed summary.

  17. Auditory change detection in fragile X syndrome males: A brain potential study

    NARCIS (Netherlands)

    van der Molen, M.J.W.; van der Molen, M.W.; Ridderinkhof, K.R.; Hamel, B.C.J.; Curfs, L.M.G.; Ramakers, G.J.A.

    2012-01-01

    OBJECTIVE: The present study investigated involuntary change detection in a two-tone pre-attentive auditory discrimination paradigm in order to better understand the information processing mechanisms underlying attention deficits in fragile X syndrome (FXS) males. METHODS: Sixteen males with the FXS

  18. Bird brains and songs : Neural mechanisms of auditory memory and perception in zebra finches

    NARCIS (Netherlands)

    Gobes, S.M.H.

    2009-01-01

    Songbirds, such as zebra finches, learn their songs from a ‘tutor’ (usually the father), early in life. There are strong parallels between the behavioural, cognitive and neural processes that underlie vocal learning in humans and songbirds. In both cases there is a sensitive period for auditory

  19. Characteristics of Auditory Agnosia in a Child with Severe Traumatic Brain Injury: A Case Report

    Science.gov (United States)

    Hattiangadi, Nina; Pillion, Joseph P.; Slomine, Beth; Christensen, James; Trovato, Melissa K.; Speedie, Lynn J.

    2005-01-01

    We present a case that is unusual in many respects from other documented incidences of auditory agnosia, including the mechanism of injury, age of the individual, and location of neurological insult. The clinical presentation is one of disturbance in the perception of spoken language, music, pitch, emotional prosody, and temporal auditory…

  20. Targeted delivery of neural stem cells to the brain using MRI-guided focused ultrasound to disrupt the blood-brain barrier.

    Directory of Open Access Journals (Sweden)

    Alison Burgess

    Full Text Available Stem cell therapy is a promising strategy to treat neurodegenerative diseases, traumatic brain injury, and stroke. For stem cells to progress towards clinical use, the risks associated with invasive intracranial surgery used to deliver the cells to the brain, needs to be reduced. Here, we show that MRI-guided focused ultrasound (MRIgFUS is a novel method for non-invasive delivery of stem cells from the blood to the brain by opening the blood brain barrier (BBB in specific brain regions. We used MRI guidance to target the ultrasound beam thereby delivering the iron-labeled, green fluorescent protein (GFP-expressing neural stem cells specifically to the striatum and the hippocampus of the rat brain. Detection of cellular iron using MRI established that the cells crossed the BBB to enter the brain. After sacrifice, 24 hours later, immunohistochemical analysis confirmed the presence of GFP-positive cells in the targeted brain regions. We determined that the neural stem cells expressed common stem cell markers (nestin and polysialic acid suggesting they survived after transplantation with MRIgFUS. Furthermore, delivered stem cells expressed doublecortin in vivo indicating the stem cells were capable of differentiating into neurons. Together, we demonstrate that transient opening of the BBB with MRIgFUS is sufficient for transplantation of stem cells from the blood to targeted brain structures. These results suggest that MRIgFUS may be an effective alternative to invasive intracranial surgery for stem cell transplantation.

  1. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

    Science.gov (United States)

    Schaefer, Jennifer E

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

  2. The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices.

    Science.gov (United States)

    Fujiwara, Katsuo; Kunita, Kenji; Kiyota, Naoe; Mammadova, Aida; Irei, Mariko

    2012-12-03

    A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10-20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections.

  3. Evaluating auditory stream segregation of SAM tone sequences by subjective and objective psychoacoustical tasks, and brain activity

    Directory of Open Access Journals (Sweden)

    Lena-Vanessa eDollezal

    2014-06-01

    Full Text Available Auditory stream segregation refers to a segregated percept of signal streams with different acoustic features. Different approaches have been pursued in studies of stream segregation. In psychoacoustics, stream segregation has mostly been investigated with a subjective task asking the subjects to report their percept. Few studies have applied an objective task in which stream segregation is evaluated indirectly by determining thresholds for a percept that depends on whether auditory streams are segregated or not. Furthermore, both perceptual measures and physiological measures of brain activity have been employed but only little is known about their relation. How the results from different tasks and measures are related is evaluated in the present study using examples relying on the ABA- stimulation paradigm that apply the same stimuli. We presented A and B signals that were sinusoidally amplitude modulated (SAM tones providing purely temporal, spectral or both types of cues to evaluate perceptual stream segregation and its physiological correlate. Which types of cues are most prominent was determined by the choice of carrier and modulation frequencies (fmod of the signals. In the subjective task subjects reported their percept and in the objective task we measured their sensitivity for detecting time-shifts of B signals in an ABA- sequence. As a further measure of processes underlying stream segregation we employed functional magnetic resonance imaging (fMRI. SAM tone parameters were chosen to evoke an integrated (1-stream, a segregated (2-stream or an ambiguous percept by adjusting the fmod difference between A and B tones (∆fmod. The results of both psychoacoustical tasks are significantly correlated. BOLD responses in fMRI depend on ∆fmod between A and B SAM tones. The effect of ∆fmod, however, differs between auditory cortex and frontal regions suggesting differences in representation related to the degree of perceptual ambiguity of

  4. Towards a truly mobile auditory brain-computer interface: exploring the P300 to take away.

    Science.gov (United States)

    De Vos, Maarten; Gandras, Katharina; Debener, Stefan

    2014-01-01

    In a previous study we presented a low-cost, small, and wireless 14-channel EEG system suitable for field recordings (Debener et al., 2012, psychophysiology). In the present follow-up study we investigated whether a single-trial P300 response can be reliably measured with this system, while subjects freely walk outdoors. Twenty healthy participants performed a three-class auditory oddball task, which included rare target and non-target distractor stimuli presented with equal probabilities of 16%. Data were recorded in a seated (control condition) and in a walking condition, both of which were realized outdoors. A significantly larger P300 event-related potential amplitude was evident for targets compared to distractors (pbrain-computer interface (BCI) study. This leads us to conclude that a truly mobile auditory BCI system is feasible. © 2013.

  5. Classification of EEG recordings in auditory brain activity via a logistic functional linear regression model.

    OpenAIRE

    Gannaz, Irène

    2014-01-01

    International audience; We want to analyse EEG recordings in order to investigate the phonemic categorization at a very early stage of auditory processing. This problem can be modelled by a supervised classification of functional data. Discrimination is explored via a logistic functional linear model, using a wavelet representation of the data. Different procedures are investigated, based on penalized likelihood and principal component reduction or partial least squares reduction.

  6. The Future Vocation of Neural Stem Cells: Lineage Commitment in Brain Development and Evolution.

    Science.gov (United States)

    Nomura, Tadashi; Gotoh, Hitoshi; Ono, Katsuhiko

    2017-08-24

    Understanding the fate commitment of neural stem cells is critical to identify the regulatory mechanisms in developing brains. Genetic lineage-tracing has provided a powerful strategy to unveil the heterogeneous nature of stem cells and their descendants. However, recent studies have reported controversial data regarding the heterogeneity of neural stem cells in the developing mouse neocortex, which prevents a decisive conclusion on this issue. Here, we review the progress that has been made using lineage-tracing analyses of the developing neocortex and discuss stem cell heterogeneity from the viewpoint of comparative and evolutionary biology.

  7. Suppression and facilitation of auditory neurons through coordinated acoustic and midbrain stimulation: investigating a deep brain stimulator for tinnitus

    Science.gov (United States)

    Offutt, Sarah J.; Ryan, Kellie J.; Konop, Alexander E.; Lim, Hubert H.

    2014-12-01

    Objective. The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined. Approach. In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs. Main Results. We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations. Significance. These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.

  8. Estimating the intended sound direction of the user: toward an auditory brain-computer interface using out-of-head sound localization.

    Directory of Open Access Journals (Sweden)

    Isao Nambu

    Full Text Available The auditory Brain-Computer Interface (BCI using electroencephalograms (EEG is a subject of intensive study. As a cue, auditory BCIs can deal with many of the characteristics of stimuli such as tone, pitch, and voices. Spatial information on auditory stimuli also provides useful information for a BCI. However, in a portable system, virtual auditory stimuli have to be presented spatially through earphones or headphones, instead of loudspeakers. We investigated the possibility of an auditory BCI using the out-of-head sound localization technique, which enables us to present virtual auditory stimuli to users from any direction, through earphones. The feasibility of a BCI using this technique was evaluated in an EEG oddball experiment and offline analysis. A virtual auditory stimulus was presented to the subject from one of six directions. Using a support vector machine, we were able to classify whether the subject attended the direction of a presented stimulus from EEG signals. The mean accuracy across subjects was 70.0% in the single-trial classification. When we used trial-averaged EEG signals as inputs to the classifier, the mean accuracy across seven subjects reached 89.5% (for 10-trial averaging. Further analysis showed that the P300 event-related potential responses from 200 to 500 ms in central and posterior regions of the brain contributed to the classification. In comparison with the results obtained from a loudspeaker experiment, we confirmed that stimulus presentation by out-of-head sound localization achieved similar event-related potential responses and classification performances. These results suggest that out-of-head sound localization enables us to provide a high-performance and loudspeaker-less portable BCI system.

  9. Brain activity underlying auditory perceptual learning during short period training: simultaneous fMRI and EEG recording

    Directory of Open Access Journals (Sweden)

    de Souza Ana Cláudia Silva

    2013-01-01

    Full Text Available Abstract Background There is an accumulating body of evidence indicating that neuronal functional specificity to basic sensory stimulation is mutable and subject to experience. Although fMRI experiments have investigated changes in brain activity after relative to before perceptual learning, brain activity during perceptual learning has not been explored. This work investigated brain activity related to auditory frequency discrimination learning using a variational Bayesian approach for source localization, during simultaneous EEG and fMRI recording. We investigated whether the practice effects are determined solely by activity in stimulus-driven mechanisms or whether high-level attentional mechanisms, which are linked to the perceptual task, control the learning process. Results The results of fMRI analyses revealed significant attention and learning related activity in left and right superior temporal gyrus STG as well as the left inferior frontal gyrus IFG. Current source localization of simultaneously recorded EEG data was estimated using a variational Bayesian method. Analysis of current localized to the left inferior frontal gyrus and the right superior temporal gyrus revealed gamma band activity correlated with behavioral performance. Conclusions Rapid improvement in task performance is accompanied by plastic changes in the sensory cortex as well as superior areas gated by selective attention. Together the fMRI and EEG results suggest that gamma band activity in the right STG and left IFG plays an important role during perceptual learning.

  10. Functional associations at global brain level during perception of an auditory illusion by applying maximal information coefficient

    Science.gov (United States)

    Bhattacharya, Joydeep; Pereda, Ernesto; Ioannou, Christos

    2018-02-01

    Maximal information coefficient (MIC) is a recently introduced information-theoretic measure of functional association with a promising potential of application to high dimensional complex data sets. Here, we applied MIC to reveal the nature of the functional associations between different brain regions during the perception of binaural beat (BB); BB is an auditory illusion occurring when two sinusoidal tones of slightly different frequency are presented separately to each ear and an illusory beat at the different frequency is perceived. We recorded sixty-four channels EEG from two groups of participants, musicians and non-musicians, during the presentation of BB, and systematically varied the frequency difference from 1 Hz to 48 Hz. Participants were also presented non-binuaral beat (NBB) stimuli, in which same frequencies were presented to both ears. Across groups, as compared to NBB, (i) BB conditions produced the most robust changes in the MIC values at the whole brain level when the frequency differences were in the classical alpha range (8-12 Hz), and (ii) the number of electrode pairs showing nonlinear associations decreased gradually with increasing frequency difference. Between groups, significant effects were found for BBs in the broad gamma frequency range (34-48 Hz), but such effects were not observed between groups during NBB. Altogether, these results revealed the nature of functional associations at the whole brain level during the binaural beat perception and demonstrated the usefulness of MIC in characterizing interregional neural dependencies.

  11. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation.

    Science.gov (United States)

    Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A

    2014-01-01

    Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico

  12. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation.

    Directory of Open Access Journals (Sweden)

    Maria eHerrojo Ruiz

    2014-09-01

    Full Text Available Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback.As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS.Overall, the present investigations are the first to demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN

  13. STEM Tones Pre-Activate Suffixes in the Brain

    Science.gov (United States)

    Söderström, Pelle; Horne, Merle; Roll, Mikael

    2017-01-01

    Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated…

  14. Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

    National Research Council Canada - National Science Library

    Yau, Shu H; McArthur, Genevieve; Badcock, Nicholas A; Brock, Jon

    2015-01-01

    .... Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech...

  15. Adult human dental pulp stem cells promote blood-brain barrier permeability through vascular endothelial growth factor-a expression.

    Science.gov (United States)

    Winderlich, Joshua N; Kremer, Karlea L; Koblar, Simon A

    2016-06-01

    Stem cell therapy is a promising new treatment option for stroke. Intravascular administration of stem cells is a valid approach as stem cells have been shown to transmigrate the blood-brain barrier. The mechanism that causes this effect has not yet been elucidated. We hypothesized that stem cells would mediate localized discontinuities in the blood-brain barrier, which would allow passage into the brain parenchyma. Here, we demonstrate that adult human dental pulp stem cells express a soluble factor that increases permeability across an in vitro model of the blood-brain barrier. This effect was shown to be the result of vascular endothelial growth factor-a. The effect could be amplified by exposing dental pulp stem cell to stromal-derived factor 1, which stimulates vascular endothelial growth factor-a expression. These findings support the use of dental pulp stem cell in therapy for stroke. © The Author(s) 2015.

  16. Instrument specific brain activation in sensorimotor and auditory representation in musicians.

    Science.gov (United States)

    Gebel, B; Braun, Ch; Kaza, E; Altenmüller, E; Lotze, M

    2013-07-01

    Musicians show a remarkable ability to interconnect motor patterns and sensory processing in the somatosensory and auditory domains. Many of these processes are specific for the instrument used. We were interested in the cerebral and cerebellar representations of these instrument-specific changes and therefore applied functional magnetic resonance imaging (fMRI) in two groups of instrumentalists with different instrumental training for comparable periods (approximately 15 years). The first group (trumpet players) uses tight finger and lip interaction; the second (pianists as control group) uses only the extremities for performance. fMRI tasks were balanced for instructions (piano and trumpet notes), sensory feedback (keypad and trumpet), and hand-lip interaction on the trumpet. During fMRI, both groups switched between different devices (trumpet or keypad) and performance was combined with or without auditory feedback. Playing the trumpet without any tone emission or using the mouthpiece showed an instrument training-specific activation increase in trumpet players. This was evident for the posterior-superior cerebellar hemisphere, the dominant primary sensorimotor cortex, and the left Heschl's gyrus. Additionally, trumpet players showed increased activity in the bilateral Heschl's gyrus during actual trumpet playing, although they showed significantly decreased loudness while playing with the mouthpiece in the scanner compared to pianists. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

    Science.gov (United States)

    Aleksandrova, M A; Marey, M V

    2015-01-01

    Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

  18. Brain-Computer Interface application: auditory serial interface to control a two-class motor-imagery-based wheelchair.

    Science.gov (United States)

    Ron-Angevin, Ricardo; Velasco-Álvarez, Francisco; Fernández-Rodríguez, Álvaro; Díaz-Estrella, Antonio; Blanca-Mena, María José; Vizcaíno-Martín, Francisco Javier

    2017-05-30

    Certain diseases affect brain areas that control the movements of the patients' body, thereby limiting their autonomy and communication capacity. Research in the field of Brain-Computer Interfaces aims to provide patients with an alternative communication channel not based on muscular activity, but on the processing of brain signals. Through these systems, subjects can control external devices such as spellers to communicate, robotic prostheses to restore limb movements, or domotic systems. The present work focus on the non-muscular control of a robotic wheelchair. A proposal to control a wheelchair through a Brain-Computer Interface based on the discrimination of only two mental tasks is presented in this study. The wheelchair displacement is performed with discrete movements. The control signals used are sensorimotor rhythms modulated through a right-hand motor imagery task or mental idle state. The peculiarity of the control system is that it is based on a serial auditory interface that provides the user with four navigation commands. The use of two mental tasks to select commands may facilitate control and reduce error rates compared to other endogenous control systems for wheelchairs. Seventeen subjects initially participated in the study; nine of them completed the three sessions of the proposed protocol. After the first calibration session, seven subjects were discarded due to a low control of their electroencephalographic signals; nine out of ten subjects controlled a virtual wheelchair during the second session; these same nine subjects achieved a medium accuracy level above 0.83 on the real wheelchair control session. The results suggest that more extensive training with the proposed control system can be an effective and safe option that will allow the displacement of a wheelchair in a controlled environment for potential users suffering from some types of motor neuron diseases.

  19. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. © The Author (2015). Published by Oxford University Press on

  20. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    2011-03-01

    Full Text Available One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem

  1. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  2. Control of abdominal muscles by brain stem respiratory neurons in the cat

    Science.gov (United States)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

  3. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  4. Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis

    Science.gov (United States)

    Kang, Zhuang; Shen, Liping; Long, Youming; Huang, Junqi; Hu, Xueqiang

    2011-01-01

    Background Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS). Objectives To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS. Methods Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. Results Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral. Conclusions Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. PMID:21853047

  5. Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Zhengqi Lu

    Full Text Available BACKGROUND: Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM, neuromyelitis optica (NMO, and multiple sclerosis (MS. OBJECTIVES: To investigate comparative brain stem lesions on magnetic resonance imaging (MRI among adult patients with ADEM, NMO, and MS. METHODS: Sixty-five adult patients with ADEM (n = 17, NMO (n = 23, and MS (n = 25 who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. RESULTS: Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001 and MS (94.1% vs. 40.0%, P<0.001; patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001 and ADEM (34.8% vs. 70.6%, P = 0.025; and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001 and MS (91.3% vs. 36.0%, P<0.001. On the axial section of the brain stem, the majority (82.4% of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%; and lesions in patients with MS were found in both the ventral (44.0% and dorsal (56.0% parts. The lesions in patients with ADEM (100% and NMO (91.3% had poorly defined margins, while lesions of patients with MS (76.0% had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%, while lesions in patients with NMO (87.0% and MS (92.0% were asymmetrical or unilateral. CONCLUSIONS: Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

  6. Stem Tones Pre-activate Suffixes in the Brain.

    Science.gov (United States)

    Söderström, Pelle; Horne, Merle; Roll, Mikael

    2017-04-01

    Results from the present event-related potentials (ERP) study show that tones on Swedish word stems can rapidly pre-activate upcoming suffixes, even when the word stem does not carry any lexical meaning. Results also show that listeners are able to rapidly restore suffixes which are replaced with a cough. Accuracy in restoring suffixes correlated positively with the amplitude of an anterior negative ERP elicited by stem tones. This effect is proposed to reflect suffix pre-activation. Suffixes that were cued by an incorrect tone elicited a left-anterior negativity and a P600, suggesting that the correct processing of the suffix is crucially tied to the activation of the preceding validly associated tone.

  7. Physics strategies for sparing neural stem cells during whole-brain radiation treatments.

    Science.gov (United States)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J

    2011-10-01

    Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  8. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143-1708 (United States)

    2011-10-15

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  9. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  10. Auditory Display

    DEFF Research Database (Denmark)

    volume. The conference's topics include auditory exploration of data via sonification and audification; real time monitoring of multivariate date; sound in immersive interfaces and teleoperation; perceptual issues in auditory display; sound in generalized computer interfaces; technologies supporting...... auditory display creation; data handling for auditory display systems; applications of auditory display....

  11. Syrinx of the Spinal Cord and Brain Stem

    Science.gov (United States)

    ... imaging (MRI) of the entire spinal cord and brain is done after paramagnetic contrast agent, such as ... neurosurgeon may make a hole in a syrinx to drain it and prevent it from expanding, but surgery ...

  12. Effect of low-frequency rTMS on electromagnetic tomography (LORETA) and regional brain metabolism (PET) in schizophrenia patients with auditory hallucinations.

    Science.gov (United States)

    Horacek, Jiri; Brunovsky, Martin; Novak, Tomas; Skrdlantova, Lucie; Klirova, Monika; Bubenikova-Valesova, Vera; Krajca, Vladimir; Tislerova, Barbora; Kopecek, Milan; Spaniel, Filip; Mohr, Pavel; Höschl, Cyril

    2007-01-01

    Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (effect of rTMS in auditory hallucinations has yet to be published. To evaluate the distribution of neuronal electrical activity and the brain metabolism changes after low-frequency rTMS in patients with auditory hallucinations. Low-frequency rTMS (0.9 Hz, 100% of motor threshold, 20 min) applied to the left temporoparietal cortex was used for 10 days in the treatment of medication-resistant auditory hallucinations in schizophrenia (n = 12). The effect of rTMS on the low-resolution brain electromagnetic tomography (LORETA) and brain metabolism ((18)FDG PET) was measured before and after 2 weeks of treatment. We found a significant improvement in the total and positive symptoms (PANSS), and on the hallucination scales (HCS, AHRS). The rTMS decreased the brain metabolism in the left superior temporal gyrus and in interconnected regions, and effected increases in the contralateral cortex and in the frontal lobes. We detected a decrease in current densities (LORETA) for the beta-1 and beta-3 bands in the left temporal lobe whereas an increase was found for beta-2 band contralaterally. Our findings implicate that the effect is connected with decreased metabolism in the cortex underlying the rTMS site, while facilitation of metabolism is propagated by transcallosal and intrahemispheric connections. The LORETA indicates that the neuroplastic changes affect the functional laterality and provide the substrate for a metabolic effect. (c) 2007 S. Karger AG, Basel.

  13. Auditory verbal hallucinations and brain dysconnectivity in the perisylvian language network: a multimodal investigation.

    Science.gov (United States)

    Benetti, Stefania; Pettersson-Yeo, William; Allen, Paul; Catani, Marco; Williams, Steven; Barsaglini, Alessio; Kambeitz-Ilankovic, Lana M; McGuire, Philip; Mechelli, Andrea

    2015-01-01

    Neuroimaging studies of schizophrenia have indicated that the development of auditory verbal hallucinations (AVHs) is associated with altered structural and functional connectivity within the perisylvian language network. However, these studies focussed mainly on either structural or functional alterations in patients with chronic schizophrenia. Therefore, they were unable to examine the relationship between the 2 types of measures and could not establish whether the observed alterations would be expressed in the early stage of the illness. We used diffusion tensor imaging and functional magnetic resonance imaging to examine white matter integrity and functional connectivity within the left perisylvian language network of 46 individuals with an at risk mental state for psychosis or a first episode of the illness, including 28 who had developed AVH group and 18 who had not (nonauditory verbal hallucination [nAVH] group), and 22 healthy controls. Inferences were made at P alterations may prevent the occurrence of the hallucinatory experience. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  14. Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture.

    Science.gov (United States)

    Kaiser, Andreas; Kale, Ajay; Novozhilova, Ekaterina; Siratirakun, Piyaporn; Aquino, Jorge B; Thonabulsombat, Charoensri; Ernfors, Patrik; Olivius, Petri

    2014-05-30

    Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  16. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro...

  17. Brain activity is related to individual differences in the number of items stored in auditory short-term memory for pitch: evidence from magnetoencephalography.

    Science.gov (United States)

    Grimault, Stephan; Nolden, Sophie; Lefebvre, Christine; Vachon, François; Hyde, Krista; Peretz, Isabelle; Zatorre, Robert; Robitaille, Nicolas; Jolicoeur, Pierre

    2014-07-01

    We used magnetoencephalography (MEG) to examine brain activity related to the maintenance of non-verbal pitch information in auditory short-term memory (ASTM). We focused on brain activity that increased with the number of items effectively held in memory by the participants during the retention interval of an auditory memory task. We used very simple acoustic materials (i.e., pure tones that varied in pitch) that minimized activation from non-ASTM related systems. MEG revealed neural activity in frontal, temporal, and parietal cortices that increased with a greater number of items effectively held in memory by the participants during the maintenance of pitch representations in ASTM. The present results reinforce the functional role of frontal and temporal cortices in the retention of pitch information in ASTM. This is the first MEG study to provide both fine spatial localization and temporal resolution on the neural mechanisms of non-verbal ASTM for pitch in relation to individual differences in the capacity of ASTM. This research contributes to a comprehensive understanding of the mechanisms mediating the representation and maintenance of basic non-verbal auditory features in the human brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Positron emission tomography (PET) analysis of the effects of auditory stimulation on the distribution of /sup 11/C-N-methylchlorphentermine in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Paschal, C.B.

    1986-06-01

    This experimental work was launched to study how auditory stimulation effects blood flow in the brain. The technique used was Positron Emission Tomography (PET) with /sup 11/C-N-methylchlorphentermine (/sup 11/C-NMCP) as the tracer. /sup 11/C-NMCP acts as a molecular microsphere and thus measures blood flow. The objectives of this work were: to develop, test, and refine an experimental procedure, to design and construct a universally applicable positioning device, and to develop and test a synthesis for a radiopure solution of /sup 11/C-NMCP; all were accomplished. PET was used to observe the brain distribution of /sup 11/C-NMCP during binaural and monaural stimulation states. The data was analyzed by finding the signal intensity in regions of the image that represented the left and right interior colliculi (IC's), brain structures dedicated to the processing of auditory signals. The binaural tests indicated a statistically significant tendency for slightly higher concentration of the tracer in the left IC than in the right IC. The monaural tests combined with those of the binaural state were not solidly conclusive, however, three of the four cases showed a decrease in tracer uptake in the IC opposite the zero-stimulus ear, as expected. There is some indication that the anesthesia used in the majority of this work may have interferred with blood flow response to auditory stimulation. 39 refs., 17 figs., 3 tabs.

  19. Role of astrocytes as neural stem cells in the adult brain

    Science.gov (United States)

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo

    2012-01-01

    In the adult mammalian brain, bona fide neural stem cells were discovered in the subventricular zone (SVZ), the largest neurogenic niche lining the striatal wall of the lateral ventricles of the brain. In this region resides a subpopulation of astrocytes that express the glial fibrillary acidic protein (GFAP), nestin and LeX. Astonishingly, these GFAP-expressing progenitors display stem-cell-like features both in vivo and in vitro. Throughout life SVZ astrocytes give rise to interneurons and oligodendrocyte precursors, which populate the olfactory bulb and the white matter, respectively. The role of the progenies of SVZ astrocytes has not been fully elucidated, but some evidence indicates that the new neurons play a role in olfactory discrimination, whereas oligodendrocytes contribute to myelinate white matter tracts. In this chapter, we describe the astrocytic nature of adult neural stem cells, their organization into the SVZ and some of their molecular and genetic characteristics. PMID:23619383

  20. Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

    Science.gov (United States)

    Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

    2018-02-14

    Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of

  1. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro (Tokushima Univ. (Japan). School of Medicine)

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author).

  2. Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

    Science.gov (United States)

    Rahman, Ruman; Heath, Rachel; Grundy, Richard

    2009-04-01

    Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

  3. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  4. Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain.

    Science.gov (United States)

    Jasmin, Jean-François; Yang, Ming; Iacovitti, Lorraine; Lisanti, Michael P

    2009-12-01

    Adult neural stem cells are self-renewing multipotent cells that have the potential to replace dysfunctional and/or dying neuronal cells at the site of brain injury or degeneration. Caveolins are well-known tumor-suppressor genes that were recently found to be involved in the regulation of stem cell proliferation. For instance, ablation of the caveolin-1 (Cav-1) gene in mice markedly increases the proliferation of intestinal and mammary stem cells. However, the roles of caveolins in the proliferation of adult neural stem cells still remain unknown. In this study, dual-label immunofluorescence analysis of the proliferation marker, Ki67, and the stem cell markers, nestin and Sox2, was performed on brains of 8 week-old wild-type (WT) and Cav-1 knockout (KO) mice. Our results demonstrate an increased number of Ki67-positive nuclei in the subventricular zone (SVZ) of Cav-1 KO brains. Importantly, our dual-label immunofluorescence analyses demonstrate increased co-localization of Ki67 with both nestin and Sox2 in the SVZ of Cav-1 KO brains. Remarkably similar results were also obtained with Cav-2 and Cav-3 KO mouse brains as well, with increased proliferation of adult neural stem cells. Thus, the SVZ of caveolin KO mouse brains displays an increased proliferation of adult neural stem cells. Caveolin proteins might represent new crucial regulators of adult neural stem cell proliferation.

  5. Brain stem evoked response audiometry of former drug users.

    Science.gov (United States)

    Weich, Tainara Milbradt; Tochetto, Tania Maria; Seligman, Lilian

    2012-10-01

    Illicit drugs are known for their deleterious effects upon the central nervous system and more specifically for how they adversely affect hearing. This study aims to analyze and compare the hearing complaints and the results of brainstem evoked response audiometry (BERA) of former drug user support group goers. This is a cross-sectional non-experimental descriptive quantitative study. The sample consisted of 17 subjects divided by their preferred drug of use. Ten individuals were placed in the marijuana group (G1) and seven in the crack/cocaine group (G2). The subjects were further divided based on how long they had been using drugs: 1 to 5 years, 6 to 10 years, and over 15 years. They were interviewed, and assessed by pure tone audiometry, acoustic impedance tests, and BERA. No statistically significant differences were found between G1 and G2 or time of drug use in absolute latencies and interpeak intervals. However, only five of the 17 individuals had BERA results with adequate results for their ages. Marijuana and crack/cocaine may cause diffuse disorders in the brainstem and compromise the transmission of auditory stimuli regardless of how long these substances are used for.

  6. Does State Merit-Based Aid Stem Brain Drain?

    Science.gov (United States)

    Zhang, Liang; Ness, Erik C.

    2010-01-01

    In this study, the authors use college enrollment and migration data to test the brain drain hypothesis. Their results suggest that state merit scholarship programs do indeed stanch the migration of "best and brightest" students to other states. In the aggregate and on average, the implementation of state merit aid programs increases the…

  7. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    ... 26-70 years) who were operated for brain astrocytomas. Immunohistochemical staining for Nestin, TP53, and Ki 67 was carried out on paraffin embedded tissue samples from the resected gliomas. Scores for markers' expression were statistically correlated with patients' age and gender, tumor grade, and patients' survival ...

  8. Eye movement preparation causes spatially-specific modulation of auditory processing: new evidence from event-related brain potentials.

    Science.gov (United States)

    Gherri, Elena; Driver, Jon; Eimer, Martin

    2008-08-11

    To investigate whether saccade preparation can modulate processing of auditory stimuli in a spatially-specific fashion, ERPs were recorded for a Saccade task, in which the direction of a prepared saccade was cued, prior to an imperative auditory stimulus indicating whether to execute or withhold that saccade. For comparison, we also ran a conventional Covert Attention task, where the same cue now indicated the direction for a covert endogenous attentional shift prior to an auditory target-nontarget discrimination. Lateralised components previously observed during cued shifts of attention (ADAN, LDAP) did not differ significantly across tasks, indicating commonalities between auditory spatial attention and oculomotor control. Moreover, in both tasks, spatially-specific modulation of auditory processing was subsequently found, with enhanced negativity for lateral auditory nontarget stimuli at cued versus uncued locations. This modulation started earlier and was more pronounced for the Covert Attention task, but was also reliably present in the Saccade task, demonstrating that the effects of covert saccade preparation on auditory processing can be similar to effects of endogenous covert attentional orienting, albeit smaller. These findings provide new evidence for similarities but also some differences between oculomotor preparation and shifts of endogenous spatial attention. They also show that saccade preparation can affect not just vision, but also sensory processing of auditory events.

  9. Aberrant brain-stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lee JH

    2016-08-01

    Full Text Available Ji Han Lee,1 Won Sang Jung,2 Woo Hee Choi,3 Hyun Kook Lim4 1Washington University in St Louis, St Louis, MO, USA; 2Department of Radiology, 3Department of Nuclear Medicine, 4Department of Psychiatry, Saint Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea Objective: Among patients with Alzheimer’s disease (AD, sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methods: In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.Results: Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.Conclusion: This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. Keywords: Alzheimer’s disease, sleep, brain stem, MRI, shape analysis

  10. Word-stem tones cue suffixes in the brain.

    Science.gov (United States)

    Roll, Mikael; Söderström, Pelle; Horne, Merle

    2013-07-03

    High and low tones on Swedish word stems are associated with different classes of suffixes. We tested the electrophysiological effects of high and low stem tones as well as tonally cued and uncued suffixes. Two different tasks were used involving either choosing the suffix-dependent meaning of the words, or pressing a button when the word ended. To determine whether effects were in fact due to association of tones with lexical material, delexicalized stimuli were also used. High tones in lexical items produced an increase in the P2 component in both tasks, interpreted as showing passive anticipatory attention allocated to the associated upcoming suffix. This effect was absent for delexicalized forms, where instead an N1 increase was found for high tones, indicating that the high pitch was unexpected in the absence of lexical material, and did not lead to anticipatory attention. A P600 effect was found for uncued high-associated suffixes in the semantic task, which was also where the largest increase was found in reaction times. This suggests that the tonal cues were most important when participants were required to process the meaning of the words. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Image analysis of neural stem cell division patterns in the zebrafish brain.

    Science.gov (United States)

    Lupperger, Valerio; Buggenthin, Felix; Chapouton, Prisca; Marr, Carsten

    2017-11-10

    Proliferating stem cells in the adult body are the source of constant regeneration. In the brain, neural stem cells (NSCs) divide to maintain the stem cell population and generate neural progenitor cells that eventually replenish mature neurons and glial cells. How much spatial coordination of NSC division and differentiation is present in a functional brain is an open question. To quantify the patterns of stem cell divisions, one has to (i) identify the pool of NSCs that have the ability to divide, (ii) determine NSCs that divide within a given time window, and (iii) analyze the degree of spatial coordination. Here, we present a bioimage informatics pipeline that automatically identifies GFP expressing NSCs in three-dimensional image stacks of zebrafish brain from whole-mount preparations. We exploit the fact that NSCs in the zebrafish hemispheres are located on a two-dimensional surface and identify between 1,500 and 2,500 NSCs in six brain hemispheres. We then determine the position of dividing NSCs in the hemisphere by EdU incorporation into cells undergoing S-phase and calculate all pairwise NSC distances with three alternative metrics. Finally, we fit a probabilistic model to the observed spatial patterns that accounts for the non-homogeneous distribution of NSCs. We find a weak positive coordination between dividing NSCs irrespective of the metric and conclude that neither strong inhibitory nor strong attractive signals drive NSC divisions in the adult zebrafish brain. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  12. The role of auditory transient and deviance processing in distraction of task performance: a combined behavioral and event-related brain potential study

    Directory of Open Access Journals (Sweden)

    Stefan eBerti

    2013-07-01

    Full Text Available Distraction of goal-oriented performance by a sudden change in the auditory environment is an everyday life experience. Different types of changes can be distracting, including a sudden onset of a transient sound and a slight deviation of otherwise regular auditory background stimulation. With regard to deviance detection, it is assumed that slight changes in a continuous sequence of auditory stimuli are detected by a predictive coding mechanisms and it has been demonstrated that this mechanism is capable of distracting ongoing task performance. In contrast, it is open whether transient detection – which does not rely on predictive coding mechanisms – can trigger behavioral distraction, too. In the present study, the effect of rare auditory changes on visual task performance is tested in an auditory-visual cross-modal distraction paradigm. The rare changes are either embedded within a continuous standard stimulation (triggering deviance detection or are presented within an otherwise silent situation (triggering transient detection. In the event-related brain potentials, deviants elicited the mismatch negativity (MMN while transients elicited an enhanced N1 component, mirroring pre-attentive change detection in both conditions but on the basis of different neuro-cognitive processes. These sensory components are followed by attention related ERP components including the P3a and the reorienting negativity (RON. This demonstrates that both types of changes trigger switches of attention. Finally, distraction of task performance is observable, too, but the impact of deviants is higher compared to transients. These findings suggest different routes of distraction allowing for the automatic processing of a wide range of potentially relevant changes in the environment as a pre-requisite for adaptive behavior.

  13. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  14. Differences in brain circuitry for appetitive and reactive aggression as revealed by realistic auditory scripts

    Directory of Open Access Journals (Sweden)

    James Kenneth Moran

    2014-12-01

    Full Text Available Aggressive behavior is thought to divide into two motivational elements: The first being a self-defensively motivated aggression against threat and a second, hedonically motivated ‘appetitive’ aggression. Appetitive aggression is the less understood of the two, often only researched within abnormal psychology. Our approach is to understand it as a universal and adaptive response, and examine the functional neural activity of ordinary men (N=50 presented with an imaginative listening task involving a murderer describing a kill. We manipulated motivational context in a between-subjects design to evoke appetitive or reactive aggression, against a neutral control, measuring activity with Magnetoencephalography (MEG. Results show differences in left frontal regions in delta (2-5 Hz and alpha band (8-12 Hz for aggressive conditions and right parietal delta activity differentiating appetitive and reactive aggression. These results validate the distinction of reward-driven appetitive aggression from reactive aggression in ordinary populations at the level of functional neural brain circuitry.

  15. Classification of Error Related Brain Activity in an Auditory Identification Task with Conditions of Varying Complexity

    Science.gov (United States)

    Kakkos, I.; Gkiatis, K.; Bromis, K.; Asvestas, P. A.; Karanasiou, I. S.; Ventouras, E. M.; Matsopoulos, G. K.

    2017-11-01

    The detection of an error is the cognitive evaluation of an action outcome that is considered undesired or mismatches an expected response. Brain activity during monitoring of correct and incorrect responses elicits Event Related Potentials (ERPs) revealing complex cerebral responses to deviant sensory stimuli. Development of accurate error detection systems is of great importance both concerning practical applications and in investigating the complex neural mechanisms of decision making. In this study, data are used from an audio identification experiment that was implemented with two levels of complexity in order to investigate neurophysiological error processing mechanisms in actors and observers. To examine and analyse the variations of the processing of erroneous sensory information for each level of complexity we employ Support Vector Machines (SVM) classifiers with various learning methods and kernels using characteristic ERP time-windowed features. For dimensionality reduction and to remove redundant features we implement a feature selection framework based on Sequential Forward Selection (SFS). The proposed method provided high accuracy in identifying correct and incorrect responses both for actors and for observers with mean accuracy of 93% and 91% respectively. Additionally, computational time was reduced and the effects of the nesting problem usually occurring in SFS of large feature sets were alleviated.

  16. Long-term meditation is associated with increased gray matter density in the brain stem

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Beek, Martijn van; Skewes, Joshua

    2009-01-01

    Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter...... density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some...... of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices....

  17. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    Science.gov (United States)

    Roll, Lars; Faissner, Andreas

    2014-01-01

    The limited regeneration capacity of the adult central nervous system (CNS) requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation. In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP) and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo. As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM), a complex network that contains numerous signaling molecules. It appears that signals in the damaged CNS lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C (TN-C). Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section. PMID:25191223

  18. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  19. Multiple cystic and focal encephalomalacia in infancy and childhood with brain stem damage.

    Science.gov (United States)

    Smith, J F; Rodeck, C

    1975-07-01

    Two cases are described in which damage to the brain stem was associated with extensive necrosis of the cerebral hemisphere. In the first case--a monochorionic twin--there was clear evidence that injury of an ischaemic or hypoxic type had occurred during fetal life and some evidence that an inadequate share of the placental circulation was an important aetiological factor. In the second case death occurred 4 yr after an asphyxial episode at birth. The lesions in the hemispheres and brain stem were extensive, although less than in the first example. The lesions are discussed in the context of our knowledge of the anatomy and physiology of the developing nervous system. Although they cannot as yet be fitted into the concepts of "critical periods" and "vulnerable periods" of development, this is perhaps because observations on human cases are scanty in comparison with the extensive animal studies which have been reported. The lesions are contrasted and compared with those seen in animals.

  20. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours.

    Science.gov (United States)

    van den Berkmortel, F; Gidding, C; De Kanter, M; Punt, C J A

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The patient was treated with high-dose chemotherapy and autologous stem cell transplantation. She developed a severe treatment-related encephalopathy which affected her quality of life and neurocognitive functioning for the rest of her life. Possible causative factors are discussed and central nervous system toxicity by high-dose chemotherapy in brain tumour patients is reviewed. Case reports on severe central nervous system toxicity have been reported, but data from prospective studies on neurocognitive functioning are not available. These data strongly support a systematic long-term follow-up of brain tumour patients treated with high-dose chemotherapy with emphasis on neurocognitive function tests.

  1. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Anna Kraft

    2017-03-01

    Full Text Available Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances.

  2. Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

    Directory of Open Access Journals (Sweden)

    Marina E. Emborg

    2013-03-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

  3. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1) assess the gastric effects of brain stem DA application, 2) identify the DA receptor subtype, and, 3) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility.NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  4. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  5. Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

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    Céline Jean-Xavier

    2018-02-01

    Full Text Available The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs during drug-induced fictive locomotor-like activity (LLA in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC and hindlimb MNs in lateral motor column (LMC. The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

  6. SOX5/6/21 Prevent Oncogene-Driven Transformation of Brain Stem Cells.

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    Kurtsdotter, Idha; Topcic, Danijal; Karlén, Alexandra; Singla, Bhumica; Hagey, Daniel W; Bergsland, Maria; Siesjö, Peter; Nistér, Monica; Carlson, Joseph W; Lefebvre, Veronique; Persson, Oscar; Holmberg, Johan; Muhr, Jonas

    2017-09-15

    Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ cells by facilitating an antiproliferative expression profile. Consistently, restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled expression of CDK inhibitors and decreased p53 protein turnover, which blocked their tumorigenic capacity through cellular senescence and apoptosis. Altogether, these results provide evidence that SOX5/6/21 play a central role in driving a tumor suppressor response in brain stem cells upon oncogenic insult. Cancer Res; 77(18); 4985-97. ©2017 AACR. ©2017 American Association for Cancer Research.

  7. Analysis of Gene Expression Profiles in the Human Brain Stem, Cerebellum and Cerebral Cortex.

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    Lei Chen

    Full Text Available The human brain is one of the most mysterious tissues in the body. Our knowledge of the human brain is limited due to the complexity of its structure and the microscopic nature of connections between brain regions and other tissues in the body. In this study, we analyzed the gene expression profiles of three brain regions-the brain stem, cerebellum and cerebral cortex-to identify genes that are differentially expressed among these different brain regions in humans and to obtain a list of robust, region-specific, differentially expressed genes by comparing the expression signatures from different individuals. Feature selection methods, specifically minimum redundancy maximum relevance and incremental feature selection, were employed to analyze the gene expression profiles. Sequential minimal optimization, a machine-learning algorithm, was employed to examine the utility of selected genes. We also performed a literature search, and we discuss the experimental evidence for the important physiological functions of several highly ranked genes, including NR2E1, DAO, and LRRC7, and we give our analyses on a gene (TFAP2B that have not been investigated or experimentally validated. As a whole, the results of our study will improve our ability to predict and understand genes related to brain regionalization and function.

  8. Bilinguals at the "cocktail party": dissociable neural activity in auditory-linguistic brain regions reveals neurobiological basis for nonnative listeners' speech-in-noise recognition deficits.

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    Bidelman, Gavin M; Dexter, Lauren

    2015-04-01

    We examined a consistent deficit observed in bilinguals: poorer speech-in-noise (SIN) comprehension for their nonnative language. We recorded neuroelectric mismatch potentials in mono- and bi-lingual listeners in response to contrastive speech sounds in noise. Behaviorally, late bilinguals required ∼10dB more favorable signal-to-noise ratios to match monolinguals' SIN abilities. Source analysis of cortical activity demonstrated monotonic increase in response latency with noise in superior temporal gyrus (STG) for both groups, suggesting parallel degradation of speech representations in auditory cortex. Contrastively, we found differential speech encoding between groups within inferior frontal gyrus (IFG)-adjacent to Broca's area-where noise delays observed in nonnative listeners were offset in monolinguals. Notably, brain-behavior correspondences double dissociated between language groups: STG activation predicted bilinguals' SIN, whereas IFG activation predicted monolinguals' performance. We infer higher-order brain areas act compensatorily to enhance impoverished sensory representations but only when degraded speech recruits linguistic brain mechanisms downstream from initial auditory-sensory inputs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The usefulness of a computerized tomographic scan taken parallel to the clivus in the management of brain-stem lesions

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    Morita, Akio; Mishima, Kazuhiko; Miyagawa, Naohisa; Aritake, Kouichi; Segawa, Hiromu; Sano, Keiji (Fuji Brain Instutue and Hospital, Shizuoka (Japan))

    1989-04-01

    It is important to detect the definite sites and extent of lesions in the management of brainstem infarction. While axial computerized tomographic scan (axial CT) has usually been used to map brain-stem lesions, it often fails to show small lesions or their longitudinal extent. In this report, the usefulness of CT scan using scan slices taken parallel to the clivus (clival CT) is evaluated in cases of brain-stem infarction. Clival CT was performed with the patient in a supine position, with as much neck flexion as possible. CT slices were taken parallel to the clivus (orbito-meatal line, 35-50 deg.). Both axial and clival CT scans were performed in 25 patients with brain-stem infarctions. Axial CT was most useful in detecting small lesions located in the ventral pons and in showing the anatomical structure which was involved. On the other hand, clival CT was superior in demonstrating the longitudinal extent of infarctions, especially in the midbrain or thalamus. In cases with major brain-stem infarctions or in cases with associated cerebellar lesions, the combination of axial and clival CT shows the configuration and continuity of the lesions clearly. Therefore, clival CT, when used with axial CT, clearly shows the three-dimensional extent of brain-stem infarctions; this technique is also recommended when managing other types of brain-stem disease. In addition, it is important to select appropriate CT slice angles in order to demonstrate the anatomical structure of interest. (author).

  10. A novel fluorescent reporter CDy1 enriches for neural stem cells derived from the murine brain.

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    Vukovic, Jana; Bedin, Anne-Sophie; Bartlett, Perry F; Osborne, Geoffrey W

    2013-08-15

    Neurogenesis occurs continuously in two brain regions of adult mammals, underpinned by a pool of resident neural stem cells (NSCs) that can differentiate into all neural cell types. To advance our understanding of NSC function and to develop therapeutic and diagnostic approaches, it is important to accurately identify and enrich for NSCs. There are no definitive markers for the identification and enrichment of NSCs present in the mouse brain. Recently, a fluorescent rosamine dye, CDy1, has been identified as a label for pluripotency in cultured human embryonic and induced pluripotent stem cells. As similar cellular characteristics may enable the uptake and retention of CDy1 by other stem cell populations, we hypothesized that this dye may also enrich for primary NSCs from the mouse brain. Because the subventricular zone (SVZ) and the hippocampus represent brain regions that are highly enriched for NSCs in adult mammals, we sampled cells from these areas to test this hypothesis. These experiments revealed that CDy1 staining indeed allows for enrichment and selection of all neurosphere-forming cells from both the SVZ and the hippocampus. We next examined the effectiveness of CDy1 to select for NSCs derived from the SVZ of aged animals, where the total pool of NSCs present is significantly lower than in young animals. We found that CDy1 effectively labels the NSCs in adult and aged animals as assessed by the neurosphere assay and reflects the numbers of NSCs present in aged animals. CDy1, therefore, appears to be a novel marker for enrichment of NSCs in primary brain tissue preparations.

  11. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

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    Cindy Leten

    2016-01-01

    Full Text Available Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683 in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI and magnetic resonance imaging (MRI. Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1 outliers can be detected earlier, (2 GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3 a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents.

  12. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

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    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  13. [Changes of EEG power spectrum in response to the emotional auditory stimuli in patients in acute and recovery stages of TBI (traumatic brain injury)].

    Science.gov (United States)

    Portnova, G V; Gladun, K V; Sharova, E A; Ivanitskiĭ, A M

    2013-01-01

    We investigated variability of responses to emotionally important auditory stimulation in different groups of TBI (Traumatic Brain Injury) in acute state or recovery. The patients sampling consisted of three different groups: patients in coma or vegetative state, patients with Severe and Moderate TBI in recovery period. Subjects were stimulated with auditory stimuli containing important physiological sounds (coughing, vomiting), emotional sounds (laughing, crying), nature sounds (bird song, barking), unpleasant household sounds (nails scratching the glass), natural sounds (sea, rain, fire) and neutral sounds (white noise). The background encephalographic activity was registered during at least 7 minutes. EEG was recorded while using portable device "Entsefalan". Significant differences of power of the rhythmic activity registered during the presentation of different types of stimuli were analyzed using Mathlab and Statistica 6.0. Results showed that EEG-response to the emotional stimuli differed depending on consciousness level, stimuli type, severity of TBI. Most valuable changes in EEG spectrum power for a patient with TBI were found for unpleasant auditory stimulation. Responsiveness to the pleasant stimulation could be registered in later stages of coming out of coma than to unpleasant stimulation. Alpha-activity is reducing in patients with TBI: the alpha rhythm depression is most evident in the control group, less in group after moderate TBI, and even less in group after severe TBI. Patients in coma or vegetative state didn't show any response in rhythmic power in the frequency of alpha rhythm.

  14. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

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    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  15. Auditory evoked potentials in patients with dementia of the Alzheimer type.

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    Grimes, A M; Grady, C L; Pikus, A

    1987-06-01

    Dementia of the Alzheimer type (DAT) disrupts the function of the central auditory nervous system as a result of temporal lobe pathology. Auditory brain stem response (ABR) and middle latency responses (MLR) were studied in a group of patients with DAT to determine whether a correlate of dementia existed in these electrophysiological potentials. Comparison of absolute and interwave latencies on ABR, and absolute latency and amplitude of the MLR in patients with DAT and normal aged controls showed no significant differences between groups for any measure. Further, no relationship with degree of dementia or temporal lobe involvement, as assessed through dichotic speech recognition studies, and auditory evoked potentials could be demonstrated. It was concluded that the temporal lobe atrophy and hypometabolism seen in DAT is not generally sufficient to disrupt the generating of ABR and MLR potentials; however, slow cortical and cognitive evoked potentials may be more sensitive to central auditory nervous system impairment in DAT.

  16. The exon junction complex component Magoh controls brain size by regulating neural stem cell division

    Science.gov (United States)

    Silver, Debra L.; Watkins-Chow, Dawn E.; Schreck, Karisa C.; Pierfelice, Tarran J.; Larson, Denise M.; Burnetti, Anthony J.; Liaw, Hung-Jiun; Myung, Kyungjae; Walsh, Christopher A.; Gaiano, Nicholas; Pavan, William J.

    2010-01-01

    Summary Brain structure and size requires precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, as do mechanistic explanations of how aberrant NSC division causes reduced brain size as seen in microcephaly. Here we demonstrate that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly due to INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number, and genomic stability. In utero rescue experiments revealed that a key function of Magoh is to control levels of the microcephaly-associated protein, LIS1, during neurogenesis. This study uncovers new requirements for the EJC in brain development, NSC maintenance, and mitosis, thus implicating this complex in the pathogenesis of microcephaly. PMID:20364144

  17. Classic and novel stem cell niches in brain homeostasis and repair.

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    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 3D culture of murine neural stem cells on decellularized mouse brain sections.

    Science.gov (United States)

    De Waele, Jorrit; Reekmans, Kristien; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

    2015-02-01

    Transplantation of neural stem cells (NSC) in diseased or injured brain tissue is widely studied as a potential treatment for various neurological pathologies. However, effective cell replacement therapy relies on the intrinsic capacity of cellular grafts to overcome hypoxic and/or immunological barriers after transplantation. In this context, it is hypothesized that structural support for grafted NSC will be of utmost importance. With this study, we present a novel decellularization protocol for 1.5 mm thick mouse brain sections, resulting in the generation of acellular three-dimensional (3D) brain sections. Next, the obtained 3D brain sections were seeded with murine NSC expressing both the eGFP and luciferase reporter proteins (NSC-eGFP/Luc). Using real-time bioluminescence imaging, the survival and growth of seeded NSC-eGFP/Luc cells was longitudinally monitored for 1-7 weeks in culture, indicating the ability of the acellular brain sections to support sustained ex vivo growth of NSC. Next, the organization of a 3D maze-like cellular structure was examined using confocal microscopy. Moreover, under mitogenic stimuli (EGF and hFGF-2), most cells in this 3D culture retained their NSC phenotype. Concluding, we here present a novel protocol for decellularization of mouse brain sections, which subsequently support long-term 3D culture of undifferentiated NSC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Brain correlates of the orientation of auditory spatial attention onto speaker location in a "cocktail-party" situation.

    Science.gov (United States)

    Lewald, Jörg; Hanenberg, Christina; Getzmann, Stephan

    2016-10-01

    Successful speech perception in complex auditory scenes with multiple competing speakers requires spatial segregation of auditory streams into perceptually distinct and coherent auditory objects and focusing of attention toward the speaker of interest. Here, we focused on the neural basis of this remarkable capacity of the human auditory system and investigated the spatiotemporal sequence of neural activity within the cortical network engaged in solving the "cocktail-party" problem. Twenty-eight subjects localized a target word in the presence of three competing sound sources. The analysis of the ERPs revealed an anterior contralateral subcomponent of the N2 (N2ac), computed as the difference waveform for targets to the left minus targets to the right. The N2ac peaked at about 500 ms after stimulus onset, and its amplitude was correlated with better localization performance. Cortical source localization for the contrast of left versus right targets at the time of the N2ac revealed a maximum in the region around left superior frontal sulcus and frontal eye field, both of which are known to be involved in processing of auditory spatial information. In addition, a posterior-contralateral late positive subcomponent (LPCpc) occurred at a latency of about 700 ms. Both these subcomponents are potential correlates of allocation of spatial attention to the target under cocktail-party conditions. © 2016 Society for Psychophysiological Research.

  20. Loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated in the young but not old brain.

    Science.gov (United States)

    Möhrle, Dorit; Ni, Kun; Varakina, Ksenya; Bing, Dan; Lee, Sze Chim; Zimmermann, Ulrike; Knipper, Marlies; Rüttiger, Lukas

    2016-08-01

    A dramatic shift in societal demographics will lead to rapid growth in the number of older people with hearing deficits. Poorer performance in suprathreshold speech understanding and temporal processing with age has been previously linked with progressing inner hair cell (IHC) synaptopathy that precedes age-dependent elevation of auditory thresholds. We compared central sound responsiveness after acoustic trauma in young, middle-aged, and older rats. We demonstrate that IHC synaptopathy progresses from middle age onward and hearing threshold becomes elevated from old age onward. Interestingly, middle-aged animals could centrally compensate for the loss of auditory fiber activity through an increase in late auditory brainstem responses (late auditory brainstem response wave) linked to shortening of central response latencies. In contrast, old animals failed to restore central responsiveness, which correlated with reduced temporal resolution in responding to amplitude changes. These findings may suggest that cochlear IHC synaptopathy with age does not necessarily induce temporal auditory coding deficits, as long as the capacity to generate neuronal gain maintains normal sound-induced central amplitudes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Mannitol-Enhanced Delivery of Stem Cells and Their Growth Factors Across the Blood–Brain Barrier

    Science.gov (United States)

    Gonzales-Portillo, Gabriel S.; Sanberg, Paul R.; Franzblau, Max; Gonzales-Portillo, Chiara; Diamandis, Theo; Staples, Meaghan; Sanberg, Cyndy D.; Borlongan, Cesar V.

    2014-01-01

    Ischemic brain injury in adults and neonates is a significant clinical problem with limited therapeutic interventions. Currently, clinicians have only tPA available for stroke treatment and hypothermia for cerebral palsy. Owing to the lack of treatment options, there is a need for novel treatments such as stem cell therapy. Various stem cells including cells from embryo, fetus, perinatal, and adult tissues have proved effective in preclinical and small clinical trials. However, a limiting factor in the success of these treatments is the delivery of the cells and their by-products (neurotrophic factors) into the injured brain. We have demonstrated that mannitol, a drug with the potential to transiently open the blood–brain barrier and facilitate the entry of stem cells and trophic factors, as a solution to the delivery problem. The combination of stem cell therapy and mannitol may improve therapeutic outcomes in adult stroke and neonatal cerebral palsy. PMID:24480552

  2. Moving on time: brain network for auditory-motor synchronization is modulated by rhythm complexity and musical training.

    Science.gov (United States)

    Chen, Joyce L; Penhune, Virginia B; Zatorre, Robert J

    2008-02-01

    Much is known about the motor system and its role in simple movement execution. However, little is understood about the neural systems underlying auditory-motor integration in the context of musical rhythm, or the enhanced ability of musicians to execute precisely timed sequences. Using functional magnetic resonance imaging, we investigated how performance and neural activity were modulated as musicians and nonmusicians tapped in synchrony with progressively more complex and less metrically structured auditory rhythms. A functionally connected network was implicated in extracting higher-order features of a rhythm's temporal structure, with the dorsal premotor cortex mediating these auditory-motor interactions. In contrast to past studies, musicians recruited the prefrontal cortex to a greater degree than nonmusicians, whereas secondary motor regions were recruited to the same extent. We argue that the superior ability of musicians to deconstruct and organize a rhythm's temporal structure relates to the greater involvement of the prefrontal cortex mediating working memory.

  3. Quantitative Evaluation of Brain Stem Atrophy Using Magnetic Resonance Imaging in Adult Patients with Alexander Disease.

    Science.gov (United States)

    Yoshida, Tomokatsu; Yasuda, Rei; Mizuta, Ikuko; Nakagawa, Masanori; Mizuno, Toshiki

    2017-01-01

    Brain MRI in adult patients with Alexander disease (AxD) mainly shows atrophy in the medulla oblongata. However, currently there is no quantitative standard for assessing this atrophy. In this study, we quantitatively evaluated the brain stem of AxD patients with glial fibrillary acidic protein (GFAP) mutation using conventional MRI to evaluate its usefulness as an aid to diagnosing AxD in daily clinical practice. Nineteen AxD patients with GFAP mutation were compared with 14 patients negative for GFAP mutation in whom AxD was suspected due to "atrophy of the medulla oblongata." In the GFAP mutation-positive group, the sagittal diameter of the medulla oblongata, the ratio of the diameter of the medulla oblongata to that of the midbrain (MO/MB), and the ratio of the sagittal diameter of the medulla oblongata to that of the pons (MO/Po) were significantly smaller compared to those of the GFAP mutation-negative group (p < 0.01). The sensitivity and specificity of each parameter were 87.5 and 92.3%, 91.7 and 81.3%, and 88.2 and 100% with a sagittal diameter of the medulla oblongata <9.0 mm, MO/MB <0.60, and sagittal MO/Po <0.46, respectively. These parameters can provide very useful information to differentially diagnose AxD from other disorders associated with brain stem atrophy in adult patients. © 2017 S. Karger AG, Basel.

  4. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

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    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  5. Long-term impact of radiation on the stem cell and oligodendrocyte precursors in the brain.

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    Georgia Panagiotakos

    Full Text Available The cellular basis of long term radiation damage in the brain is not fully understood.We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries.This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursors and the inability of the stem cell compartment to compensate for this loss.

  6. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage.

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    van Velthoven, Cindy T J; Kavelaars, Annemieke; Heijnen, Cobi J

    2012-04-01

    Mesenchymal stem cell (MSC)-based therapies have been proven effective in experimental models of numerous disorders. Treatment of ischemic brain injury by transplantation of MSCs in neonatal animal models has been shown to be effective in reducing lesion volume and improving functional outcome. The beneficial effect of MSC transplantation to treat neonatal brain injury might be explained by the great plasticity of the neonatal brain. The neonatal brain is still in a developmentally active phase, leading to a better efficiency of MSC transplantation than that observed in experiments using adult models of stroke. Enhanced neurogenesis and axonal remodeling likely underlie the improved functional outcome following MSC treatment after neonatal hypoxic-ischemic (HI) brain injury. With respect to the mechanism of repair by MSCs, MSCs do not survive long term and replace damaged tissue themselves. We propose that MSCs react to the needs of the ischemic cerebral environment by secretion of several growth factors, cytokines, and other bioactive molecules to regulate damage and repair processes. Parenchymal cells react to the secretome of the MSCs and contribute to stimulate repair processes. These intrinsic adaptive properties of MSCs make them excellent candidates for a novel therapy to treat the devastating effects of HI encephalopathy in the human neonate.

  7. Stemming the Impact of Health Professional Brain Drain from Africa: A Systemic Review of Policy Options.

    Science.gov (United States)

    Zimbudzi, Edward

    2013-06-25

    Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

  8. Stemming the impact of health professional brain drain from Africa: a systemic review of policy options

    Directory of Open Access Journals (Sweden)

    Edward Zimbudzi

    2013-06-01

    Full Text Available Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

  9. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic......-culture, large numbers of tyrosine hydroxylase (TH)-immunoreactive, catecholaminergic cells could be found underneath individual striatal slices. Cell counting revealed that up to 25.3% (average 16.1%) of the total number of cells in these areas were TH-positive, contrasting a few TH-positive cells (

  10. Circumventricular organs: a novel site of neural stem cells in the adult brain.

    Science.gov (United States)

    Bennett, Lori; Yang, Ming; Enikolopov, Grigori; Iacovitti, Lorraine

    2009-07-01

    Neurogenesis in the adult mammalian nervous system is now well established in the subventricular zone of the anterolateral ventricle and subgranular zone of the hippocampus. In these regions, neurons are thought to arise from neural stem cells, identified by their expression of specific intermediate filament proteins (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study, we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich in nestin+, GFAP+, vimentin+ cells which express Sox2 and the cell cycle-regulating protein Ki67. In culture, these cells proliferate as neurospheres and express neuronal (doublecortin+, beta-tubulin III+) and glial (S100beta+, GFAP+, RIP+) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine show that CVO cells proliferate and undergo constitutive neurogenesis and gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown source of stem/progenitor cells, capable of giving rise to new neurons and/or glia in the adult brain.

  11. The extracellular matrix niche microenvironment of neural and cancer stem cells in the brain.

    Science.gov (United States)

    Reinhard, Jacqueline; Brösicke, Nicole; Theocharidis, Ursula; Faissner, Andreas

    2016-12-01

    Numerous studies demonstrated that neural stem cells and cancer stem cells (NSCs/CSCs) share several overlapping characteristics such as self-renewal, multipotency and a comparable molecular repertoire. In addition to the intrinsic cellular properties, NSCs/CSCs favor a similar environment to acquire and maintain their characteristics. In the present review, we highlight the shared properties of NSCs and CSCs in regard to their extracellular microenvironment called the NSC/CSC niche. Moreover, we point out that extracellular matrix (ECM) molecules and their complementary receptors influence the behavior of NSCs/CSCs as well as brain tumor progression. Here, we focus on the expression profile and functional importance of the ECM glycoprotein tenascin-C, the chondroitin sulfate proteoglycan DSD-1-PG/phosphacan but also on other important glycoprotein/proteoglycan constituents. Within this review, we specifically concentrate on glioblastoma multiforme (GBM). GBM is the most common malignant brain tumor in adults and is associated with poor prognosis despite intense and aggressive surgical and therapeutic treatment. Recent studies indicate that GBM onset is driven by a subpopulation of CSCs that display self-renewal and recapitulate tumor heterogeneity. Based on the CSC hypothesis the cancer arises just from a small subpopulation of self-sustaining cancer cells with the exclusive ability to self-renew and maintain the tumor. Besides the fundamental stem cell properties of self-renewal and multipotency, GBM stem cells share further molecular characteristics with NSCs, which we would like to review in this article. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Dosimetric analysis of trigeminal nerve, brain stem doses in CyberKnife radiosurgery of trigeminal neuralgia.

    Science.gov (United States)

    Sudahar, H; Kurup, P G G; Murali, V; Velmurugan, J

    2012-07-01

    CyberKnife radiosurgery treatment of Trigeminal neuralgia (TN) is performed as a non-invasive image guided procedure. The prescription dose for TN is very high. The brainstem is the adjacent critical organ at risk (OAR) which is prone to receive the very high target dose of TN. The present study is to analyze the dose distribution inside the tiny trigeminal nerve target and also to analyze the dose fall off in the brain stem. Seven TN cases treated between November 2010 and January 2012 were taken for this study retrospectively. The treatment plans were analyzed for target dose conformity, homogeneity and dose coverage. In the brainstem the volume doses D(1%), D(2%) were taken for analyzing the higher doses in the brain stem. The dose fall off was analyzed in terms of D(5%) and D(10%). The mean value of maximum dose within the trigeminal nerve target was 73.5±2.1Gy (P=0.0007) and the minimum dose was 50.0±4.1Gy (P=0.1315). The mean conformity index was 2.19 and the probable reason could be the smallest CyberKnife collimator of 5mm used in the treatment plan. The mean D(1%), of the brainstem was 10.5± 2.1Gy (P=0.5316) and the mean value of the maximum point dose within the brainstem was 35.6±3.8Gy. This shows the degree of dose fall off within the brainstem. Though the results of the present study are showing superior sparing of brain stem and reasonable of target coverage, it is necessary to execute the treatment plan with greater accuracy in CyberKnife as the immobilization is noninvasive and frameless.

  13. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Directory of Open Access Journals (Sweden)

    Thomas Jubault

    Full Text Available Idiopathic Parkinson's disease (PD is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia. Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3 in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  14. Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.

    Science.gov (United States)

    Xiong, Liu-Lin; Hu, Yue; Zhang, Piao; Zhang, Zhuo; Li, Li-Hong; Gao, Guo-Dong; Zhou, Xin-Fu; Wang, Ting-Hua

    2017-04-18

    Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10 5 /μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-β were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.

  15. Cortical Evoked Potentials and Hearing Aids in Individuals with Auditory Dys-Synchrony.

    Science.gov (United States)

    Yuvaraj, Pradeep; Mannarukrishnaiah, Jayaram

    2015-12-01

    The purpose of the present study was to investigate the relationship between cortical processing of speech and benefit from hearing aids in individuals with auditory dys-synchrony. Data were collected from 38 individuals with auditory dys-synchrony. Participants were selected based on hearing thresholds, middle ear reflexes, otoacoustic emissions, and auditory brain stem responses. Cortical-evoked potentials were recorded for click and speech. Participants with auditory dys-synchrony were fitted with bilateral multichannel wide dynamic range compression hearing aids. Aided and unaided speech identification scores for 40 words were obtained for each participant. Hierarchical cluster analysis using Ward's method clearly showed four subgroups of participants with auditory dys-synchrony based on the hearing aid benefit score (aided minus unaided speech identification score). The difference in the mean aided and unaided speech identification scores was significantly different in participants with auditory dys-synchrony. However, the mean unaided speech identification scores were not significantly different between the four subgroups. The N2 amplitude and P1 latency of the speech-evoked cortical potentials were significantly different between the four subgroups formed based on hearing aid benefit scores. The results indicated that subgroups of individuals with auditory dys-synchrony who benefit from hearing aids exist. Individuals who benefitted from hearing aids showed decreased N2 amplitudes compared with those who did not. N2 amplitude is associated with greater suppression of background noise while processing speech.

  16. Neural stem cells sustain natural killer cells that dictate recovery from brain inflammation

    Science.gov (United States)

    Liu, Qiang; Sanai, Nader; Jin, Wei-Na; La Cava, Antonio; Van Kaer, Luc; Shi, Fu-Dong

    2017-01-01

    Recovery from organ-specific autoimmune diseases largely relies on the mobilization of endogenous repair mechanisms and local factors that control them. Natural killer (NK) cells are swiftly mobilized to organs targeted by autoimmunity and typically undergo numerical contraction when inflammation wanes. We report the unexpected finding that NK cells are retained in the brain subventricular zone (SVZ) during the chronic phase of multiple sclerosis in humans and its animal model in mice. These NK cells were found preferentially in close proximity to SVZ neural stem cells (NSCs) that produce interleukin-15 and sustain functionally competent NK cells. Moreover, NK cells limited the reparative capacity of NSCs following brain inflammation. These findings reveal that reciprocal interactions between NSCs and NK cells regulate neurorepair. PMID:26752157

  17. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain.

    Science.gov (United States)

    Espuny-Camacho, Ira; Arranz, Amaia M; Fiers, Mark; Snellinx, An; Ando, Kunie; Munck, Sebastian; Bonnefont, Jerome; Lambot, Laurie; Corthout, Nikky; Omodho, Lorna; Vanden Eynden, Elke; Radaelli, Enrico; Tesseur, Ina; Wray, Selina; Ebneth, Andreas; Hardy, John; Leroy, Karelle; Brion, Jean-Pierre; Vanderhaeghen, Pierre; De Strooper, Bart

    2017-03-08

    Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration. Remarkably, cell death was dissociated from tangle formation in this natural 3D model of AD. Using genome-wide expression analysis, we observed upregulation of genes involved in myelination and downregulation of genes related to memory and cognition, synaptic transmission, and neuron projection. This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  19. Non-auditory Effect of Noise Pollution and Its Risk on Human Brain Activity in Different Audio Frequency Using Electroencephalogram Complexity.

    Science.gov (United States)

    Allahverdy, Armin; Jafari, Amir Homayoun

    2016-10-01

    Noise pollution is one of the most harmful ambiance disturbances. It may cause many deficits in ability and activity of persons in the urban and industrial areas. It also may cause many kinds of psychopathies. Therefore, it is very important to measure the risk of this pollution in different area. This study was conducted in the Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences from June to September of 2015, in which, different frequencies of noise pollution were played for volunteers. 16-channel EEG signal was recorded synchronously, then by using fractal dimension and relative power of Beta sub-band of EEG, the complexity of EEG signals was measured. As the results, it is observed that the average complexity of brain activity is increased in the middle of audio frequency range and the complexity map of brain activity changes in different frequencies, which can show the effects of frequency changes on human brain activity. The complexity of EEG is a good measure for ranking the annoyance and non-auditory risk of noise pollution on human brain activity.

  20. Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells.

    Science.gov (United States)

    Vangipuram, Sharada D; Lyman, William D

    2010-09-01

    Prenatal ethanol (ETOH) exposure can lead to fetal alcohol spectrum disorder (FASD). We previously showed that ETOH alters cell adhesion molecule gene expression and increases neurosphere size in fetal brain-derived neural stem cells (NSC). Here, our aim was to determine the effect of ETOH on the cell fate of NSC, premature glial-committed precursor cells (GCP), and premature neuron-committed progenitor cells (NCP). NSC, GCP, and NCP were isolated from normal second-trimester fetal human brains (n = 3) by positive selection using magnetic microbeads labeled with antibodies to CD133 (NSC), A2B5 (GCP), or PSA-NCAM (NCP). As a result of the small percentage in each brain, NSC were cultured in mitogenic media for 72 hours to produce neurospheres. The neurospheres from NSC and primary isolates of GCP and NCP were used for all experiments. Equal numbers of the 3 cell types were treated either with mitogenic media or with differentiating media, each containing 0 or 100 mM ETOH, for 120 hours. Expression of Map2a, GFAP, and O4 was determined by immunoflourescence microscopy and western blot analysis. Fluorescence intensities were quantified using Metamorph software by Molecular Devices, and the bands of western blots were quantified using densitometry. ETOH in mitogenic media promoted formation of neurospheres by NSC, GCP, and NCP. Under control conditions, GCP attached and differentiated, NSC and NCP formed neurospheres that were significantly smaller in size than those in ETOH. Under differentiating conditions, Map2a expression increased significantly in NSC and GCP and reduced significantly in NCP, and GFAP expression reduced significantly in GCP and NCP, and Gal-C expression reduced significantly in all 3 cell types in the presence of ETOH compared to controls. This study shows that ETOH alters the cell fate of neuronal stem and progenitor cells. These alterations could contribute to the mechanism for the abnormal brain development in FASD.

  1. Evoked brain potentials and disability in brain-damaged patients.

    Science.gov (United States)

    Rappaport, M; Hall, K; Hopkins, K; Belleza, T; Berrol, S; Reynolds, G

    1977-08-01

    Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

  2. Sex differences in morphology of the brain stem and cerebellum with normal ageing

    Energy Technology Data Exchange (ETDEWEB)

    Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S. [Internal Medicine III, Shimane Medical University, Izumo (Japan)

    1998-12-01

    The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.) With 4 figs., 3 tabs., 16 refs.

  3. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  4. An auditory multiclass brain-computer interface with natural stimuli: usability evaluation with healthy participants and a motor impaired end user

    Directory of Open Access Journals (Sweden)

    Nadine eSimon

    2015-01-01

    Full Text Available Brain-computer interfaces (BCIs can serve as muscle independent communication aids. Persons, who are unable to control their eye muscles (e.g. in the completely locked-in state or have severe visual impairments for other reasons, need BCI systems that do not rely on the visual modality. For this reason, BCIs that employ auditory stimuli were suggested. In this study, a multiclass BCI spelling system was implemented that uses animal voices with directional cues to code rows and columns of a letter matrix. To reveal possible training effects with the system, 11 healthy participants performed spelling tasks on two consecutive days. In a second step, the system was tested by a participant with amyotrophic lateral sclerosis (ALS in two sessions. In the first session, healthy participants spelled with an average accuracy of 76% (3.29 bits/min that increased to 90% (4.23 bits/min on the second day. Spelling accuracy by the participant with ALS was 20% in the first and 47% in the second session. The results indicate a strong training effect for both the healthy participants and the participant with ALS. While healthy participants reached high accuracies in the first session and second session, accuracies for the participant with ALS were not sufficient for satisfactory communication in both sessions. More training sessions might be needed to improve spelling accuracies. The study demonstrated the feasibility of the auditory BCI with healthy users and stresses the importance of training with auditory multiclass BCIs, especially for potential end-users of BCI with disease.

  5. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  6. Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells.

    Science.gov (United States)

    Kraft, Anna; Jubal, Eduardo Rosales; von Laer, Ruth; Döring, Claudia; Rocha, Adriana; Grebbin, Moyo; Zenke, Martin; Kettenmann, Helmut; Stroh, Albrecht; Momma, Stefan

    2017-03-14

    Brain injuries, such as stroke or trauma, induce neural stem cells in the subventricular zone (SVZ) to a neurogenic response. Very little is known about the molecular cues that signal tissue damage, even over large distances, to the SVZ. Based on our analysis of gene expression patterns in the SVZ, 48 hr after an ischemic lesion caused by middle cerebral artery occlusion, we hypothesized that the presence of an injury might be transmitted by an astrocytic traveling calcium wave rather than by diffusible factors or hypoxia. Using a newly established in vitro system we show that calcium waves induced in an astrocytic monolayer spread to neural stem and progenitor cells and increase their self-renewal as well as migratory behavior. These changes are due to an upregulation of the Notch signaling pathway. This introduces the concept of propagating astrocytic calcium waves transmitting brain injury signals over long distances. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  8. Human-Avatar Symbiosis for the Treatment of Auditory Verbal Hallucinations in Schizophrenia through Virtual/Augmented Reality and Brain-Computer Interfaces

    Directory of Open Access Journals (Sweden)

    Antonio Fernández-Caballero

    2017-11-01

    Full Text Available This perspective paper faces the future of alternative treatments that take advantage of a social and cognitive approach with regards to pharmacological therapy of auditory verbal hallucinations (AVH in patients with schizophrenia. AVH are the perception of voices in the absence of auditory stimulation and represents a severe mental health symptom. Virtual/augmented reality (VR/AR and brain computer interfaces (BCI are technologies that are growing more and more in different medical and psychological applications. Our position is that their combined use in computer-based therapies offers still unforeseen possibilities for the treatment of physical and mental disabilities. This is why, the paper expects that researchers and clinicians undergo a pathway toward human-avatar symbiosis for AVH by taking full advantage of new technologies. This outlook supposes to address challenging issues in the understanding of non-pharmacological treatment of schizophrenia-related disorders and the exploitation of VR/AR and BCI to achieve a real human-avatar symbiosis.

  9. Human-Avatar Symbiosis for the Treatment of Auditory Verbal Hallucinations in Schizophrenia through Virtual/Augmented Reality and Brain-Computer Interfaces.

    Science.gov (United States)

    Fernández-Caballero, Antonio; Navarro, Elena; Fernández-Sotos, Patricia; González, Pascual; Ricarte, Jorge J; Latorre, José M; Rodriguez-Jimenez, Roberto

    2017-01-01

    This perspective paper faces the future of alternative treatments that take advantage of a social and cognitive approach with regards to pharmacological therapy of auditory verbal hallucinations (AVH) in patients with schizophrenia. AVH are the perception of voices in the absence of auditory stimulation and represents a severe mental health symptom. Virtual/augmented reality (VR/AR) and brain computer interfaces (BCI) are technologies that are growing more and more in different medical and psychological applications. Our position is that their combined use in computer-based therapies offers still unforeseen possibilities for the treatment of physical and mental disabilities. This is why, the paper expects that researchers and clinicians undergo a pathway toward human-avatar symbiosis for AVH by taking full advantage of new technologies. This outlook supposes to address challenging issues in the understanding of non-pharmacological treatment of schizophrenia-related disorders and the exploitation of VR/AR and BCI to achieve a real human-avatar symbiosis.

  10. Human-Avatar Symbiosis for the Treatment of Auditory Verbal Hallucinations in Schizophrenia through Virtual/Augmented Reality and Brain-Computer Interfaces

    Science.gov (United States)

    Fernández-Caballero, Antonio; Navarro, Elena; Fernández-Sotos, Patricia; González, Pascual; Ricarte, Jorge J.; Latorre, José M.; Rodriguez-Jimenez, Roberto

    2017-01-01

    This perspective paper faces the future of alternative treatments that take advantage of a social and cognitive approach with regards to pharmacological therapy of auditory verbal hallucinations (AVH) in patients with schizophrenia. AVH are the perception of voices in the absence of auditory stimulation and represents a severe mental health symptom. Virtual/augmented reality (VR/AR) and brain computer interfaces (BCI) are technologies that are growing more and more in different medical and psychological applications. Our position is that their combined use in computer-based therapies offers still unforeseen possibilities for the treatment of physical and mental disabilities. This is why, the paper expects that researchers and clinicians undergo a pathway toward human-avatar symbiosis for AVH by taking full advantage of new technologies. This outlook supposes to address challenging issues in the understanding of non-pharmacological treatment of schizophrenia-related disorders and the exploitation of VR/AR and BCI to achieve a real human-avatar symbiosis. PMID:29209193

  11. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

    Science.gov (United States)

    Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

    2015-10-01

    Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation

  12. Targeted activation of primitive neural stem cells in the mouse brain.

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    Reeve, Rachel L; Yammine, Samantha Z; DeVeale, Brian; van der Kooy, Derek

    2016-06-01

    Primitive neural stem cells (pNSCs) are the earliest NSCs to appear in the developing forebrain. They persist into the adult forebrain where they can generate all cells in the neural lineage and therefore hold great potential for brain regeneration. Thus, pNSCs are an ideal population to target to promote endogenous NSC activation. pNSCs can be isolated from the periventricular region as leukaemia inhibitory factor-responsive cells, and comprise a rare population in the adult mouse brain. We hypothesized that the pup periventricular region gives rise to more clonal pNSC-derived neurospheres but that pup-derived pNSCs are otherwise comparable to adult-derived pNSCs, and can be used to identify selective markers and activators of endogenous pNSCs. We tested the self-renewal ability, differentiation capacity and gene expression profile of pup-derived pNSCs and found them each to be comparable to adult-derived pNSCs, including being GFAP(-) , nestin(mid) , Oct4(+) . Next, we used pup pNSCs to test pharmacological compounds to activate pNSCs to promote endogenous brain repair. We hypothesized that pNSCs could be activated by targeting the cell surface proteins C-Kit and ErbB2, which were enriched in pNSCs relative to definitive NSCs (dNSCs) in an in vitro screen. C-Kit and ErbB2 signalling inhibition had distinct effects on pNSCs and dNSCs in vitro, and when infused directly into the adult brain in vivo. Targeted activation of pNSCs with C-Kit and ErbB2 modulation is a valuable strategy to activate the earliest cell in the neural lineage to contribute to endogenous brain regeneration. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.

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    Joon W Shim

    Full Text Available Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2 that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive control, and a 90-min tail suspension was used as a stress (negative control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC, ventromedial hypothalamus (VMH, and brain stem (BS. We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.

  14. Auditory and Visual Sensations

    CERN Document Server

    Ando, Yoichi

    2010-01-01

    Professor Yoichi Ando, acoustic architectural designer of the Kirishima International Concert Hall in Japan, presents a comprehensive rational-scientific approach to designing performance spaces. His theory is based on systematic psychoacoustical observations of spatial hearing and listener preferences, whose neuronal correlates are observed in the neurophysiology of the human brain. A correlation-based model of neuronal signal processing in the central auditory system is proposed in which temporal sensations (pitch, timbre, loudness, duration) are represented by an internal autocorrelation representation, and spatial sensations (sound location, size, diffuseness related to envelopment) are represented by an internal interaural crosscorrelation function. Together these two internal central auditory representations account for the basic auditory qualities that are relevant for listening to music and speech in indoor performance spaces. Observed psychological and neurophysiological commonalities between auditor...

  15. Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

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    Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hyo-Jeong; Huh, Yang Hoon; Cho, Seong-Wan; Lee, Jin-Koo; Kim, Hyung-Gun; Kim, Hak Rim

    2017-01-01

    The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

  16. Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells.

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    Stebbins, Matthew J; Wilson, Hannah K; Canfield, Scott G; Qian, Tongcheng; Palecek, Sean P; Shusta, Eric V

    2016-05-15

    The blood-brain barrier (BBB) is a critical component of the central nervous system (CNS) that regulates the flux of material between the blood and the brain. Because of its barrier properties, the BBB creates a bottleneck to CNS drug delivery. Human in vitro BBB models offer a potential tool to screen pharmaceutical libraries for CNS penetration as well as for BBB modulators in development and disease, yet primary and immortalized models respectively lack scalability and robust phenotypes. Recently, in vitro BBB models derived from human pluripotent stem cells (hPSCs) have helped overcome these challenges by providing a scalable and renewable source of human brain microvascular endothelial cells (BMECs). We have demonstrated that hPSC-derived BMECs exhibit robust structural and functional characteristics reminiscent of the in vivo BBB. Here, we provide a detailed description of the methods required to differentiate and functionally characterize hPSC-derived BMECs to facilitate their widespread use in downstream applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

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    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  18. Impact of Repetitive Transcranial Magnetic Stimulation (rTMS on Brain Functional Marker of Auditory Hallucinations in Schizophrenia Patients

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    Sonia Dollfus

    2013-04-01

    Full Text Available Several cross-sectional functional Magnetic Resonance Imaging (fMRI studies reported a negative correlation between auditory verbal hallucination (AVH severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS. Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS cluster, considered henceforward as a functional region of interest (fROI. After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities.

  19. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury.

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    Drommelschmidt, Karla; Serdar, Meray; Bendix, Ivo; Herz, Josephine; Bertling, Frederik; Prager, Sebastian; Keller, Matthias; Ludwig, Anna-Kristin; Duhan, Vikas; Radtke, Stefan; de Miroschedji, Kyra; Horn, Peter A; van de Looij, Yohan; Giebel, Bernd; Felderhoff-Müser, Ursula

    2017-02-01

    Preterm brain injury is a major cause of disability in later life, and may result in motor, cognitive and behavioural impairment for which no treatment is currently available. The aetiology is considered as multifactorial, and one underlying key player is inflammation leading to white and grey matter injury. Extracellular vesicles secreted by mesenchymal stem/stromal cells (MSC-EVs) have shown therapeutic potential in regenerative medicine. Here, we investigated the effects of MSC-EV treatment on brain microstructure and maturation, inflammatory processes and long-time outcome in a rodent model of inflammation-induced brain injury. 3-Day-old Wistar rats (P3) were intraperitoneally injected with 0.25mg/kg lipopolysaccharide or saline and treated with two repetitive doses of 1×10 8 cell equivalents of MSC-EVs per kg bodyweight. Cellular degeneration and reactive gliosis at P5 and myelination at P11 were evaluated by immunohistochemistry and western blot. Long-term cognitive and motor function was assessed by behavioural testing. Diffusion tensor imaging at P125 evaluated long-term microstructural white matter alterations. MSC-EV treatment significantly ameliorated inflammation-induced neuronal cellular degeneration reduced microgliosis and prevented reactive astrogliosis. Short-term myelination deficits and long-term microstructural abnormalities of the white matter were restored by MSC-EV administration. Morphological effects of MSC-EV treatment resulted in improved long-lasting cognitive functions INTERPRETATION: MSC-EVs ameliorate inflammation-induced cellular damage in a rat model of preterm brain injury. MSC-EVs may serve as a novel therapeutic option by prevention of neuronal cell death, restoration of white matter microstructure, reduction of gliosis and long-term functional improvement. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications

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    Marci G Crowley

    2017-01-01

    Full Text Available Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA-approved drug in place for stroke patients, tissue plasminogen activator (tPA, has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem

  1. Severe Spastic Trismus without Generalized Spasticity after Unilateral Brain Stem Stroke

    Science.gov (United States)

    Seo, Jong-Hyun; Kang, Si Hyun; Seo, Kyung-Mook; Seok, Ju Won

    2012-01-01

    A 62-year-old female patient diagnosed with left brain stem stroke 2 months ago was admitted to our clinic for rehabilitation. She had no generalized spasticity on both extremities, but could open her mouth only approximately 2 mm between her upper and lower teeth due to severe trismus. On needle electromyography, the left masseter muscle showed paradoxically increased muscle activity during mouth opening. We injected 50 units of type A botulinum toxin (Botox®) into the left masseter muscle, and 20 units into the left temporalis muscle with guidance of ultrasonography. The interincisal distance increased to 8 mm on the 3rd day after injection, and 9 mm on the 4th day. One month later, the interincisal distance increased to 14 mm. The increased interincisal distance was maintained for 13 months after injection, and the quality of hygienic care and compliance of oral stimulation therapy also improved. PMID:22506250

  2. Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

    Science.gov (United States)

    Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

    1998-01-01

    A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

  3. Overlap of saccadic and pursuit eye movement systems in the brain stem reticular formation.

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    Yan, Y J; Cui, D M; Lynch, J C

    2001-12-01

    Recent physiological studies have suggested that there are several sites of interaction between the neural pathways that control saccadic eye movements and those that control visual pursuit movements. To address the question of saccade/pursuit interaction from a neuroanatomical point of view, we have studied the connections from the smooth and saccadic eye movement subregions of the frontal eye field (FEFsem and FEFsac, respectively) to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in four Cebus apella monkeys. The riMLF has traditionally been considered to be a premotor center for vertical saccadic eye movements on the basis of single neuron recording experiments, microstimulation experiments, and surgical or chemical lesion experiments. We localized the functional subregions of the FEF with the use of low-threshold (smooth pursuit eye movements and supports the hypothesis that there is interaction between the saccadic and pursuit subsystems at the brain stem level.

  4. Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.

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    Alice Y W Chang

    Full Text Available BACKGROUND: Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM, a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation. METHODOLOGY/PRINCIPAL FINDINGS: An animal model of brain stem death employing the pesticide mevinphos as the experimental insult in Sprague-Dawley rats was used. Intravenous administration of lethal doses of mevinphos elicited an abrupt cardiac arrest, accompanied by elevated systemic arterial pressure and anoxia, augmented neuronal excitability and enhanced microvascular perfusion in RVLM. This period represents the vital time-window between cardiac arrest and resumption of spontaneous circulation in our experimental model. Animals with restored spontaneous circulation exhibited maintained neuronal functionality in RVLM beyond this critical time-window, alongside resumption of baseline tissue oxygen and enhancement of local blood flow. Intriguingly, animals that subsequently died manifested sustained anoxia, diminished local blood flow, depressed mitochondrial electron transport activities and reduced ATP production, leading to necrotic cell death in RVLM. That amelioration of mitochondrial dysfunction and

  5. Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells.

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    Choi, Seung Ah; Lee, Ji Yeoun; Kwon, Sung Eun; Wang, Kyu-Chang; Phi, Ji Hoon; Choi, Jung Won; Jin, Xiong; Lim, Ja Yun; Kim, Hyunggee; Kim, Seung-Ki

    2015-01-01

    In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.

  6. Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.

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    Faith C H Li

    Full Text Available BACKGROUND: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH, the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM, which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. METHODOLOGY/PRINCIPAL FINDINGS: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54. CONCLUSION: We conclude that sustained anoxia and cessation of local blood flow

  7. Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain.

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    Amort, Thomas; Rieder, Dietmar; Wille, Alexandra; Khokhlova-Cubberley, Daria; Riml, Christian; Trixl, Lukas; Jia, Xi-Yu; Micura, Ronald; Lusser, Alexandra

    2017-01-05

    Recent work has identified and mapped a range of posttranscriptional modifications in mRNA, including methylation of the N6 and N1 positions in adenine, pseudouridylation, and methylation of carbon 5 in cytosine (m5C). However, knowledge about the prevalence and transcriptome-wide distribution of m5C is still extremely limited; thus, studies in different cell types, tissues, and organisms are needed to gain insight into possible functions of this modification and implications for other regulatory processes. We have carried out an unbiased global analysis of m5C in total and nuclear poly(A) RNA of mouse embryonic stem cells and murine brain. We show that there are intriguing differences in these samples and cell compartments with respect to the degree of methylation, functional classification of methylated transcripts, and position bias within the transcript. Specifically, we observe a pronounced accumulation of m5C sites in the vicinity of the translational start codon, depletion in coding sequences, and mixed patterns of enrichment in the 3' UTR. Degree and pattern of methylation distinguish transcripts modified in both embryonic stem cells and brain from those methylated in either one of the samples. We also analyze potential correlations between m5C and micro RNA target sites, binding sites of RNA binding proteins, and N6-methyladenosine. Our study presents the first comprehensive picture of cytosine methylation in the epitranscriptome of pluripotent and differentiated stages in the mouse. These data provide an invaluable resource for future studies of function and biological significance of m5C in mRNA in mammals.

  8. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

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    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  9. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Evaluation of central auditory discrimination abilities in older adults.

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    Claudia eFreigang

    2011-05-01

    Full Text Available The present study focuses on auditory discrimination abilities in older adults aged 65-89 years. We applied the ‘Leipzig Inventory for Patient Psychoacoustic’ (LIPP, a psychoacoustic test battery specifically designed to identify deficits in central auditory processing. These tests quantify the just noticeable differences (JND for the three basic acoustic parameters (i.e. frequency, intensity, and signal duration. Three different test modes (monaural, dichotic signal/noise [s/n] and interaural were used, stimulus level was 35dB sensation level. The tests are designed as three-alternative forced-choice procedure with a maximum-likelihood procedure estimating p=0,5 correct response value. These procedures have proven to be highly efficient and provide a reliable outcome. The measurements yielded significant age-dependent deteriorations in the ability to discriminate single acoustic features pointing to progressive impairments in central auditory processing. The degree of deterioration was correlated to the different acoustic features and to the test modes. Most prominent, interaural frequency and signal duration discrimination at low test frequencies was elevated which indicates a deterioration of time- and phase-dependent processing at brain stem and cortical levels. LIPP proves to be an effective tool to identify basic pathophysiological mechanisms and the source of a specific impairment in auditory processing of the elderly.

  11. Classification of Auditory Evoked Potentials based on the wavelet decomposition and SVM network

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    Michał Suchocki

    2015-12-01

    Full Text Available For electrophysiological hearing assessment and diagnosis of brain stem lesions, the most often used are auditory brainstem evoked potentials of short latency. They are characterized by successively arranged maxima as a function of time, called waves. Morphology of the course, in particular, the timing and amplitude of each wave, allow a neurologist to make diagnose, what is not an easy task. A neurologist should be experienced, concentrated, and should have very good perception. In order to support his diagnostic process, the authors have developed an algorithm implementing the automated classification of auditory evoked potentials to the group of pathological and physiological cases, the sensitivity and specificity determined for an independent test group (of 50 cases of respectively 84% and 88%.[b]Keywords[/b]: biomedical engineering, brainstem auditory evoked potentials, wavelet decomposition, support vector machine

  12. Recovery from a possible cytomegalovirus meningoencephalitis-induced apparent brain stem death in an immunocompetent man: a case report.

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    Rahardjo, Theresia Monica; Maskoen, Tinni Trihartini; Redjeki, Ike Sri

    2016-08-26

    Recovery from cytomegalovirus meningoencephalitis with brain stem death in an immunocompetent patient is almost impossible. We present a remarkable recovery from a possible cytomegalovirus infection in an immunocompetent man who had severe neurological syndromes, suggesting brain stem death complicated by pneumonia and pleural effusion. A 19-year-old Asian man presented at our hospital's emergency department with reduced consciousness and seizures following high fever, headache, confusion, and vomitus within a week before arrival. He was intubated and sent to our intensive care unit. He had nuchal rigidity and tetraparesis with accentuated tendon reflexes. Electroencephalography findings suggested an acute structural lesion at his right temporal area or an epileptic state. A cerebral spinal fluid examination suggested viral infection. A computed tomography scan was normal at the early stage of disease. Immunoglobulin M, immunoglobulin G anti-herpes simplex virus, and immunoglobulin M anti-cytomegalovirus were negative. However, immunoglobulin G anti-cytomegalovirus was positive, which supported a diagnosis of cytomegalovirus meningoencephalitis. His clinical condition deteriorated, spontaneous respiration disappeared, cranial reflexes became negative, and brain stem death was suspected. Therapy included antivirals, corticosteroids, antibiotics, anticonvulsant, antipyretics, antifungal agents, and a vasopressor to maintain hemodynamic stability. After 1 month, he showed a vague response to painful stimuli at his supraorbital nerve and respiration started to appear the following week. After pneumonia and pleural effusion were resolved, he was weaned from the ventilator and moved from the intensive care unit on day 90. This case highlights several important issues that should be considered. First, the diagnosis of brain stem death must be confirmed with caution even if there are negative results of brain stem death test for a long period. Second, cytomegalovirus

  13. Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

    Science.gov (United States)

    Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

    2014-01-06

    Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

  14. Salicylate-Induced Suppression of Electrically Driven Activity in Brain Slices from the Auditory Cortex of Aging Mice

    Directory of Open Access Journals (Sweden)

    Minoru Namikawa

    2017-12-01

    Full Text Available The prevalence of tinnitus is known to increase with age. The age-dependent mechanisms of tinnitus may have important implications for the development of new therapeutic treatments. High doses of salicylate can be used experimentally to induce transient tinnitus and hearing loss. Although accumulating evidence indicates that salicylate induces tinnitus by directly targeting neurons in the peripheral and central auditory systems, the precise effect of salicylate on neural networks in the auditory cortex (AC is unknown. Here, we examined salicylate-induced changes in stimulus-driven laminar responses of AC slices with salicylate superfusion in young and aged senescence-accelerated-prone (SAMP and -resistant (SAMR mice. Of the two strains, SAMP1 is known to be a more suitable model of presbycusis. We recorded stimulus-driven laminar local field potential (LFP responses at multi sites in AC slice preparations. We found that for all AC slices in the two strains, salicylate always reduced stimulus-driven LFP responses in all layers. However, for the amplitudes of the LFP responses, the two senescence-accelerated mice (SAM strains showed different laminar properties between the pre- and post-salicylate conditions, reflecting strain-related differences in local circuits. As for the relationships between auditory brainstem response (ABR thresholds and the LFP amplitude ratios in the pre- vs. post-salicylate condition, we found negative correlations in layers 2/3 and 4 for both older strains, and in layer 5 (L5 in older SAMR1. In contrast, the GABAergic agonist muscimol (MSC led to positive correlations between ABR thresholds and LFP amplitude ratios in the pre- vs. post-MSC condition in younger SAM mice from both strains. Further, in younger mice, salicylate decreased the firing rate in AC L4 pyramidal neurons. Thus, salicylate can directly reduce neural excitability of L4 pyramidal neurons and thereby influence AC neural circuit activity. That we

  15. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment★

    Science.gov (United States)

    Wang, Xianying; Wu, Honghai; Xue, Gai; Hou, Yanning

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment. PMID:25624820

  16. [Deep-seated (corpus callosum, intraventricular, basal ganglia and insula) and brain stem cavernous angiomas. Experience in Brazil].

    Science.gov (United States)

    Alves de Sousa, A

    2007-06-01

    With a review of the literature, we report our experience with surgical treatment of deep-seated cavernomas (intraventricular, of the corpus callosum, the capsula interna, the insula and the brain stem). Outcome was good in all nine patients after surgery for deep-seated brain cavernomas. There we also 13 cases of the brain stem cavernomas treated surgically. Of them, nine patients were stabilized or improved, one patient worsened, one patient died and two were lost to follow-up. Whatever the location, surgery should only concern symptomatic or hemorrhagic lesions close to the pia-matter or the ependyma as well as those covered by a thin layer of parenchyma. Neuronavigation and microsurgical procedures are essential in the treatment of deep-seated cavernomas.

  17. Longer storage of auditory than of visual information in the rabbit brain: evidence from dorsal hippocampal electrophysiology.

    Science.gov (United States)

    Astikainen, Piia; Ruusuvirta, Timo; Korhonen, Tapani

    2005-01-01

    Whereas sensory memory in humans has been found to store auditory information for a longer time than visual information, it is unclear whether this is the case also in other species. We recorded hippocampal event-related potentials (ERPs) in awake rabbits exposed to occasional changes in a repeated 50-ms acoustic (1000 versus 2000 Hz) and visual (vertical versus horizontal orientation) stimulus. Three intervals (500, 1500, or 3000 ms) between stimulus repetitions were applied. Whereas acoustic changes significantly affected ERPs with the repetition intervals of 500 and 1500 ms, visual changes did so only with the repetition interval of 500 ms. Our finding, thus, suggests a similarity in sensory processing abilities between human and non-human mammals.

  18. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

    DEFF Research Database (Denmark)

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders

    2016-01-01

    relative to a group of Controls to basic motor, perceptual, executive and adaptation tasks. Participants (N: KS=49; Controls=49) responded to whether the words “GREEN” or “RED” were displayed in green or red (incongruent versus congruent colors). One of the colors was presented three times as often...... with the widespread dyslexia in the group. No neural differences were found in inhibitory control (Stroop) or in adaptation to differences in stimulus frequencies. Across groups we found a strong positive correlation between age and BOLD response in the brain’s motor network with no difference between groups...... as the other, making it possible to study both congruency and adaptation effects independently. Auditory stimuli saying “GREEN” or “RED” had the same distribution, making it possible to study effects of perceptual modality as well as Frequency effects across modalities. We found that KS had an increased...

  19. Implicit learning of predictable sound sequences modulates human brain responses at different levels of the auditory hierarchy

    Directory of Open Access Journals (Sweden)

    Françoise eLecaignard

    2015-09-01

    Full Text Available Deviant stimuli, violating regularities in a sensory environment, elicit the Mismatch Negativity (MMN, largely described in the Event-Related Potential literature. While it is widely accepted that the MMN reflects more than basic change detection, a comprehensive description of mental processes modulating this response is still lacking. Within the framework of predictive coding, deviance processing is part of an inference process where prediction errors (the mismatch between incoming sensations and predictions established through experience are minimized. In this view, the MMN is a measure of prediction error, which yields specific expectations regarding its modulations by various experimental factors. In particular, it predicts that the MMN should decrease as the occurrence of a deviance becomes more predictable. We conducted a passive oddball EEG study and manipulated the predictability of sound sequences by means of different temporal structures. Importantly, our design allows comparing mismatch responses elicited by predictable and unpredictable violations of a simple repetition rule and therefore departs from previous studies that investigate violations of different time-scale regularities. We observed a decrease of the MMN with predictability and interestingly, a similar effect at earlier latencies, within 70 ms after deviance onset. Following these pre-attentive responses, a reduced P3a was measured in the case of predictable deviants. We conclude that early and late deviance responses reflect prediction errors, triggering belief updating within the auditory hierarchy. Beside, in this passive study, such perceptual inference appears to be modulated by higher-level implicit learning of sequence statistical structures. Our findings argue for a hierarchical model of auditory processing where predictive coding enables implicit extraction of environmental regularities.

  20. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R. [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Maderwald, Stefan [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Linn, Jennifer; Bochmann, Katja [LMU Munich, Department of Neuroradiology, Munich (Germany); Dassinger, Benjamin [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Justus-Liebig-University Giessen, Department of Neuroradiology, Giessen (Germany); Forsting, Michael [University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2014-03-15

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  1. Gold nanoparticle-cell labeling methodology for tracking stem cells within the brain

    Science.gov (United States)

    Betzer, Oshra; Meir, Rinat; Motiei, Menachem; Yadid, Gal; Popovtzer, Rachela

    2017-02-01

    Cell therapy provides a promising approach for diseases and injuries that conventional therapies cannot cure effectively. Mesenchymal stem cells (MSCs) can be used as effective targeted therapy, as they exhibit homing capabilities to sites of injury and inflammation, exert anti-inflammatory effects, and can differentiate in order to regenerate damaged tissue. Despite the potential efficacy of cell therapy, applying cell-based therapy in clinical practice is very challenging; there is a need to uncover the mystery regarding the fate of the transplanted cells. Therefore, in this study, we developed a method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), and combined with gold nanoparticles as labeling agents. We applied this technique for non-invasive imaging of MSCs transplanted in a rat model for depression, a highly prevalent and disabling neuropsychiatric disorder lacking effective treatment. Our results, which demonstrate that cell migration could be detected as early as 24 hours and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression related brain regions. This research further reveals that cell therapy is a beneficial approach for treating neuropsychiatric disorders; Behavioral manifestations of core symptoms of depressive behavior, were significantly attenuated following treatment. We expect This CT-based technique to lead to a significant enhancement in cellular therapy both for basic research and clinical applications of brain pathologies.

  2. Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis

    Directory of Open Access Journals (Sweden)

    Huan Liao

    2017-01-01

    Full Text Available Radiation-induced brain injury (RI commonly occurs in patients who received head and neck radiotherapy. However, the mechanism of RI remains unclear. We aimed to evaluate whether pyroptosis was involved in RI and the impact of mesenchymal stem cells (MSCs on it. BALB/c male mice (6–8 weeks were cranially irradiated (15 Gy, and MSCs were transplanted into the bilateral cortex 2 days later; then mice were sacrificed 1 month later. Meanwhile, irradiated BV-2 microglia cells (10 Gy were cocultured with MSCs for 24 hours. We observed that irradiated mice brains presented NLRP3 and caspase-1 activation. RT-PCR then indicated that it mainly occurred in microglia cells but not in neurons. Further, irradiated BV-2 cells showed pyroptosis and increased production of IL-18 and IL-1β. RT-PCR also demonstrated an increased expression of several inflammasome genes in irradiated BV-2 cells, including NLRP3 and AIM2. Particularly, NLRP3 was activated. Knockdown of NLRP3 resulted in decreased LDH release. Noteworthily, in vivo, MSCs transplantation alleviated radiation-induced NLRP3 and caspase-1 activation. Moreover, in vitro, MSCs could decrease caspase-1 dependent pyroptosis, NLRP3 inflammasome activation, and ROS production induced by radiation. Thus, our findings proved that microglia pyroptosis occurred in RI. MSCs may act as a potent therapeutic tool in attenuating pyroptosis.

  3. Preferred EEG brain states at stimulus onset in a fixed interstimulus interval equiprobable auditory Go/NoGo task: a definitive study.

    Science.gov (United States)

    Barry, Robert J; De Blasio, Frances M; De Pascalis, Vilfredo; Karamacoska, Diana

    2014-10-01

    This study examined the occurrence of preferred EEG phase states at stimulus onset in an equiprobable auditory Go/NoGo task with a fixed interstimulus interval, and their effects on the resultant event-related potentials (ERPs). We used a sliding short-time FFT decomposition of the EEG at Cz for each trial to assess prestimulus EEG activity in the delta, theta, alpha and beta bands. We determined the phase of each 2 Hz narrow-band contributing to these four broad bands at 125 ms before each stimulus onset, and for the first time, avoided contamination from poststimulus EEG activity. This phase value was extrapolated 125 ms to obtain the phase at stimulus onset, combined into the broad-band phase, and used to sort trials into four phase groups for each of the four broad bands. For each band, ERPs were derived for each phase from the raw EEG activity at 19 sites. Data sets from each band were separately decomposed using temporal Principal Components Analyses with unrestricted VARIMAX rotation to extract N1-1, PN, P2, P3, SW and LP components. Each component was analysed as a function of EEG phase at stimulus onset in the context of a simple conceptualisation of orthogonal phase effects (cortical negativity vs. positivity, negative driving vs. positive driving, waxing vs. waning). The predicted non-random occurrence of phase-defined brain states was confirmed. The preferred states of negativity, negative driving, and waxing were each associated with more efficient stimulus processing, as reflected in amplitude differences of the components. The present results confirm the existence of preferred brain states and their impact on the efficiency of brain dynamics in perceptual and cognitive processing. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

    Science.gov (United States)

    Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

    2017-03-01

    Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-01-23

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018. © AlphaMed Press 2018.

  6. Auditory assessment of children with severe hearing loss using behavioural observation audiometry and brainstem evoked response audiometry

    OpenAIRE

    Rakhi Kumari; Priyanko Chakraborty; Jain, R K; Dhananjay Kumar

    2016-01-01

    Background: Early detection of hearing loss has been a long-standing priority in the field of audiology. Currently available auditory testing methods include both behavioural and non-behavioural or objective tests of hearing. This study was planned with an objective to assess hearing loss in children using behavioural observation audiometry and brain stem evoked response audiometry. Methods: A total of 105 cases suffering from severe to profound hearing loss were registered. After proper h...

  7. Klinefelter syndrome has increased brain responses to auditory stimuli and motor output, but not to visual stimuli or Stroop adaptation

    DEFF Research Database (Denmark)

    Wallentin, Mikkel; Skakkebæk, Anne; Bojesen, Anders

    2016-01-01

    Klinefelter syndrome (47, XXY) (KS) is a genetic syndrome characterized by the presence of an extra X chromosome and low level of testosterone, resulting in a number of neurocognitive abnormalities, yet little is known about brain function. This study investigated the fMRI-BOLD response from KS...

  8. Prostaglandin E2 Indicates Therapeutic Efficacy of Mesenchymal Stem Cells in Experimental Traumatic Brain Injury.

    Science.gov (United States)

    Kota, Daniel J; Prabhakara, Karthik S; Toledano-Furman, Naama; Bhattarai, Deepa; Chen, Qingzheng; DiCarlo, Bryan; Smith, Philippa; Triolo, Fabio; Wenzel, Pamela L; Cox, Charles S; Olson, Scott D

    2017-05-01

    Traumatic brain injury (TBI) is soon predicted to become the third leading cause of death and disability worldwide. After the primary injury, a complex set of secondary injuries develops hours and days later with prolonged neuroinflammation playing a key role. TBI and other inflammatory conditions are currently being treated in preclinical and clinical trials by a number of cellular therapies. Mesenchymal stem cells (MSC) are of great interest due to their widespread usage, safety, and relative ease to isolate and culture. However, there has been a wide range in efficacy reported using MSC clinically and in preclinical models, likely due to differences in cell preparations and a significant amount of donor variability. In this study, we seek to find a correlation between in vitro activity and in vivo efficacy. We designed assays to explore the responsiveness of MSC to immunological cues to address the immunomodulatory properties of MSC, one of their primary modes of therapeutic activity in TBI. Our results showed intrinsic differences in the immunomodulatory capacity of MSC preparations from different bone marrow and amniotic fluid donors. This difference mirrored the therapeutic capacity of the MSC in an experimental model of TBI, an effect confirmed using siRNA knockdown of COX2 followed by overexpressing COX2. Among the immunomodulatory factors assessed, the therapeutic benefit correlated with the secretion of prostaglandin E2 (PGE2 ) by MSC prior to treatment, suggesting that measurement of PGE2 could be a very useful potency marker to create an index of predicted efficacy for preparations of MSC to treat TBI. Stem Cells 2017;35:1416-1430. © 2017 AlphaMed Press.

  9. A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

    Science.gov (United States)

    Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

    2014-06-15

    A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

  10. STEM?!?!

    Science.gov (United States)

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  11. Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer's Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Na Kyung Lee

    Full Text Available Mesenchymal stem cells (MSCs have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD. Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB-MSCs into the brains of non-transgenic WT (C3H/C57 and transgenic AD (APP/PS1 mice through the intra-arterial (IA route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1 or 5 minutes (experiment 2 after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD.

  12. Presenilins are required for maintenance of neural stem cells in the developing brain

    Directory of Open Access Journals (Sweden)

    Kim Woo-Young

    2008-01-01

    Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

  13. Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

    Science.gov (United States)

    Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

    2014-11-01

    The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

  14. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  15. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|.

    Science.gov (United States)

    Ho, Nguyen Thi Thanh; Kutzner, Arne; Heese, Klaus

    2017-12-20

    Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity. Insight into the specific regulation of the brain-specific neural master gene |-SRGAP2-FAM72-| may essentially contribute to novel therapeutic approaches to restore or improve higher cognitive functions.

  16. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Science.gov (United States)

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  17. Brain stem activity changes associated with restored sympathetic drive following CPAP treatment in OSA subjects: a longitudinal investigation.

    Science.gov (United States)

    Lundblad, Linda C; Fatouleh, Rania H; McKenzie, David K; Macefield, Vaughan G; Henderson, Luke A

    2015-08-01

    Obstructive sleep apnea (OSA) is associated with significantly elevated muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. Although little is known about the mechanisms responsible for the sympathoexcitation, we have recently shown that the elevated MSNA in OSA is associated with altered neural processing in various brain stem sites, including the dorsolateral pons, rostral ventrolateral medulla, medullary raphe, and midbrain. Given the risk associated with elevated MSNA, we aimed to determine if treatment of OSA with continuous positive airway pressure (CPAP) would reduce the elevated MSNA and reverse the brain stem functional changes associated with the elevated MSNA. We performed concurrent recordings of MSNA and blood oxygen level-dependent (BOLD) signal intensity of the brain stem, using high-resolution functional magnetic resonance imaging, in 15 controls and 13 subjects with OSA, before and after 6 mo CPAP treatment. As expected, 6 mo of CPAP treatment significantly reduced MSNA in subjects with OSA, from 54 ± 4 to 23 ± 3 bursts/min and from 77 ± 7 to 36 ± 3 bursts/100 heart beats. Importantly, we found that MSNA-coupled changes in BOLD signal intensity within the dorsolateral pons, medullary raphe, and rostral ventrolateral medulla returned to control levels. That is, CPAP treatment completely reversed brain stem functional changes associated with elevated MSNA in untreated OSA subjects. These data highlight the effectiveness of CPAP treatment in reducing one of the most significant health issues associated with OSA, that is, elevated MSNA and its associated elevated morbidity. Copyright © 2015 the American Physiological Society.

  18. Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat.

    Science.gov (United States)

    Jones, Sarah E; Dutschmann, Mathias

    2016-05-01

    Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. Copyright © 2016 the American Physiological Society.

  19. Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting

    Directory of Open Access Journals (Sweden)

    Sabbagh Abdulrahman

    2009-01-01

    Full Text Available This report describes a rare case of ventrally exophytic pontine glioma describing operative and neuroanesthesia management. The combination of intraoperative neuromonitoring was used. It constituted: Brain stem evoked responses/potentials, Motor EP: recording from cranial nerve supplied muscle, and Sensory EP: Medial/tibial. Excision of the tumor was done with intra-operative magnatic resonance imaging (iMRI, which is considered a new modality.

  20. CRISPR/Cas9-induced disruption of gene expression in mouse embryonic brain and single neural stem cells in vivo.

    Science.gov (United States)

    Kalebic, Nereo; Taverna, Elena; Tavano, Stefania; Wong, Fong Kuan; Suchold, Dana; Winkler, Sylke; Huttner, Wieland B; Sarov, Mihail

    2016-03-01

    We have applied the CRISPR/Cas9 system in vivo to disrupt gene expression in neural stem cells in the developing mammalian brain. Two days after in utero electroporation of a single plasmid encoding Cas9 and an appropriate guide RNA (gRNA) into the embryonic neocortex of Tis21::GFP knock-in mice, expression of GFP, which occurs specifically in neural stem cells committed to neurogenesis, was found to be nearly completely (≈ 90%) abolished in the progeny of the targeted cells. Importantly, upon in utero electroporation directly of recombinant Cas9/gRNA complex, near-maximal efficiency of disruption of GFP expression was achieved already after 24 h. Furthermore, by using microinjection of the Cas9 protein/gRNA complex into neural stem cells in organotypic slice culture, we obtained disruption of GFP expression within a single cell cycle. Finally, we used either Cas9 plasmid in utero electroporation or Cas9 protein complex microinjection to disrupt the expression of Eomes/Tbr2, a gene fundamental for neocortical neurogenesis. This resulted in a reduction in basal progenitors and an increase in neuronal differentiation. Thus, the present in vivo application of the CRISPR/Cas9 system in neural stem cells provides a rapid, efficient and enduring disruption of expression of specific genes to dissect their role in mammalian brain development. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  1. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.

    Science.gov (United States)

    Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E

    2014-03-01

    Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.

  2. Susceptibility-weighted imaging of the venous networks around the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Ming; Lin, Zhong-Xiao; Zhang, Nu [Wenzhou Medical University, Department of Neurosurgery, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China); Zhang, Xiao-Fen; Qiao, Hui-Huang; Chen, Cheng-Chun [Wenzhou Medical University, Department of Human Anatomy, Wenzhou (China); Ren, Chuan-Gen; Li, Jian-Ce [Wenzhou Medical University, Department of Radiology, The 1nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China)

    2014-10-18

    The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100 %). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75 % of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region. (orig.)

  3. Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

    Science.gov (United States)

    Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

    2016-05-01

    Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  4. Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats.

    Science.gov (United States)

    Amini, Naser; Vousooghi, Nasim; Hadjighassem, Mahmoudreza; Bakhtiyari, Mehrdad; Mousavi, Neda; Safakheil, Hosein; Jafari, Leila; Sarveazad, Arash; Yari, Abazar; Ramezani, Sara; Faghihi, Faezeh; Joghataei, Mohammad Taghi

    2016-05-01

    Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.

  5. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

    Science.gov (United States)

    Mangraviti, Antonella; Tzeng, Stephany Y; Gullotti, David; Kozielski, Kristen L; Kim, Jennifer E; Seng, Michael; Abbadi, Sara; Schiapparelli, Paula; Sarabia-Estrada, Rachel; Vescovi, Angelo; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J; Quinones-Hinojosa, Alfredo

    2016-09-01

    There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Synaptic mechanisms underlying interaural level difference selectivity in rat auditory cortex

    Science.gov (United States)

    Kyweriga, Michael; Stewart, Whitney; Cahill, Carolyn

    2014-01-01

    The interaural level difference (ILD) is a sound localization cue that is extensively processed in the auditory brain stem and midbrain and is also represented in the auditory cortex. Here, we asked whether neurons in the auditory cortex passively inherit their ILD tuning from subcortical sources or whether their spiking preferences were actively shaped by local inhibition. If inherited, the ILD selectivity of spiking output should match that of excitatory synaptic input. If shaped by local inhibition, by contrast, excitation should be more broadly tuned than spiking output with inhibition suppressing spiking for nonpreferred stimuli. To distinguish between these two processing strategies, we compared spiking responses with excitation and inhibition in the same neurons across a range of ILDs and average binaural sound levels. We found that cells preferring contralateral ILDs (often called EI cells) followed the inheritance strategy. In contrast, cells that were unresponsive to monaural sounds but responded predominantly to near-zero ILDs (PB cells) instead showed evidence of the local processing strategy. These PB cells received excitatory inputs that were similar to those received by the EI cells. However, contralateral monaural sounds and ILDs >0 dB elicited strong inhibition, quenching the spiking output. These results suggest that in the rat auditory cortex, EI cells do not utilize inhibition to shape ILD sensitivity, whereas PB cells do. We conclude that an auditory cortical circuit computes sensitivity for near-zero ILDs. PMID:25185807

  7. Harmonic Training and the formation of pitch representation in a neural network model of the auditory brain

    Directory of Open Access Journals (Sweden)

    Nasir eAhmad

    2016-03-01

    Full Text Available Attempting to explain the perceptual qualities of pitch has proven to be, and remains, a difficult problem. The wide range of sounds which illicit pitch and a lack of agreement across neurophysiological studies on how pitch is encoded by the brain have made this attempt more difficult. In describing the potential neural mechanisms by which pitch may be processed, a number of neural networks have been proposed and implemented. However, no unsupervised neural networks with biologically accurate cochlear inputs have yet been demonstrated. This paper proposes a simplified system in which pitch representing neurons are easily produced under a highly biological setting. Purely unsupervised regimes of neural network learning are implemented and these prove to be sufficient in identifying the pitch of sounds with a variety of spectral profiles, including missing fundamental sounds.

  8. Impaired auditory selective attention ameliorated by cognitive training with graded exposure to noise in patients with traumatic brain injury.

    Science.gov (United States)

    Dundon, Neil M; Dockree, Suvi P; Buckley, Vanessa; Merriman, Niamh; Carton, Mary; Clarke, Sarah; Roche, Richard A P; Lalor, Edmund C; Robertson, Ian H; Dockree, Paul M

    2015-08-01

    Patients who suffer traumatic brain injury frequently report difficulty concentrating on tasks and completing routine activities in noisy and distracting environments. Such impairments can have long-term negative psychosocial consequences. A cognitive control function that may underlie this impairment is the capacity to select a goal-relevant signal for further processing while safeguarding it from irrelevant noise. A paradigmatic investigation of this problem was undertaken using a dichotic listening task (study 1) in which comprehension of a stream of speech to one ear was measured in the context of increasing interference from a second stream of irrelevant speech to the other ear. Controls showed an initial decline in performance in the presence of competing speech but thereafter showed adaptation to increasing audibility of irrelevant speech, even at the highest levels of noise. By contrast, patients showed linear decline in performance with increasing noise. Subsequently attempts were made to ameliorate this deficit (study 2) using a cognitive training procedure based on attention process training (APT) that included graded exposure to irrelevant noise over the course of training. Patients were assigned to adaptive and non-adaptive training schedules or to a no-training control group. Results showed that both types of training drove improvements in the dichotic listening and in naturalistic tasks of performance in noise. Improvements were also seen on measures of selective attention in the visual domain suggesting transfer of training. We also observed augmentation of event-related potentials (ERPs) linked to target processing (P3b) but no change in ERPs evoked by distractor stimuli (P3a) suggesting that training heightened tuning of target signals, as opposed to gating irrelevant noise. No changes in any of the above measures were observed in a no-training control group. Together these findings present an ecologically valid approach to measure selective

  9. Asymmetric excitatory synaptic dynamics underlie interaural time difference processing in the auditory system.

    Directory of Open Access Journals (Sweden)

    Pablo E Jercog

    2010-06-01

    Full Text Available Low-frequency sound localization depends on the neural computation of interaural time differences (ITD and relies on neurons in the auditory brain stem that integrate synaptic inputs delivered by the ipsi- and contralateral auditory pathways that start at the two ears. The first auditory neurons that respond selectively to ITD are found in the medial superior olivary nucleus (MSO. We identified a new mechanism for ITD coding using a brain slice preparation that preserves the binaural inputs to the MSO. There was an internal latency difference for the two excitatory pathways that would, if left uncompensated, position the ITD response function too far outside the physiological range to be useful for estimating ITD. We demonstrate, and support using a biophysically based computational model, that a bilateral asymmetry in excitatory post-synaptic potential (EPSP slopes provides a robust compensatory delay mechanism due to differential activation of low threshold potassium conductance on these inputs and permits MSO neurons to encode physiological ITDs. We suggest, more generally, that the dependence of spike probability on rate of depolarization, as in these auditory neurons, provides a mechanism for temporal order discrimination between EPSPs.

  10. PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes.

    Science.gov (United States)

    Choi, Insup; Choi, Dong-Joo; Yang, Haijie; Woo, Joo Hong; Chang, Mi-Yoon; Kim, Joo Yeon; Sun, Woong; Park, Sang-Myun; Jou, Ilo; Lee, Sang-Hun; Lee, Sang Hoon; Joe, Eun-Hye

    2016-01-08

    Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson's disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD.

  11. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  12. Auditory short-term memory in the primate auditory cortex.

    Science.gov (United States)

    Scott, Brian H; Mishkin, Mortimer

    2016-06-01

    Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

  13. Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development.

    Science.gov (United States)

    Viktorin, Gudrun; Riebli, Nadia; Popkova, Anna; Giangrande, Angela; Reichert, Heinrich

    2011-08-15

    The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

    Science.gov (United States)

    St John, James A; Walkden, Heidi; Nazareth, Lynn; Beagley, Kenneth W; Ulett, Glen C; Batzloff, Michael R; Beacham, Ifor R; Ekberg, Jenny A K

    2016-09-01

    Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  15. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina.

    Science.gov (United States)

    Zhou, Xue-mei; Yuan, Hui-ping; Wu, Dong-lai; Zhou, Xin-rong; Sun, Da-wei; Li, Hong-yi; Shao, Zheng-bo

    2009-07-20

    Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P neuron more efficiently compared with the control NSCs 2 months after transplantation. The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in the normal host retinas.

  16. Gamma knife radiosurgery of the symptomatic brain stem cavernous angioma with low marginal dose.

    Science.gov (United States)

    Kim, Byung Sup; Yeon, Je Young; Kim, Jong-Soo; Hong, Seung-Chyul; Lee, Jung-Il

    2014-11-01

    To analyze the outcome of gamma knife radiosurgery (GKS) using low marginal dose for the symptomatic brain stem cavernous angioma (BSCA). 39 patients (16 males, 23 females) were treated with GKS for BSCA from January 1997 to September 2012. Clinical data were analyzed retrospectively. The mean age was 41.5 years. All patients had a history of symptomatic bleeding once or more before performing GKS. Mean volume of BSCA was 1095.3mm(3) and median prescribed marginal dose was 13 Gy. Mean follow-up period since diagnosis was 4.1 years. The number of hemorrhagic events between initial diagnosis and GKS was 5 over a total of 14.9 patients-years with annual hemorrhagic rate of 33.6%. Following GKS, there were five hemorrhagic events within the first 2 years (8.1%/year) and two after the first 2 years (2.4%/year). The difference was not statistically significant. Neurologic status improved in 24 patients (61.5%), and stationary in eleven (28.2%). 4 patients (10.3%) experienced the exacerbation of symptoms at the last follow-up and none of them were related to the radiation injury. Significant volume reduction after GKS was observed in 24 patients (61.5%). Surgical excision was performed in one patient due to swelling and rebleeding after GKS. Age at presentation, sex, mass size of BSCA, and location, GKS dose did not affect post-GKS hemorrhage. GKS for BSCA using relatively low marginal dose is safe and effective. Long-term prospective study is needed to confirm the optimal dose for BSCA. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Evaluation of an auditory brainstem response in icteric neonates

    Directory of Open Access Journals (Sweden)

    Ahmad Talebian

    2017-08-01

    Full Text Available Background: Neonatal hyperbilirubinemia is a common and preventable cause of sensory-neural hearing impairment, which can cause difficulties in the development of speech and communication. This study was conducted to detect the toxic effect of hyperbilirubinemia on the brain stem and auditory tract in neonates with icterus admitted to Shahid Beheshti Hospital in Kashan, Iran. Materials and Methods: This cross-sectional study was conducted on 98 neonates with increased indirect bilirubin admitted to Shahid Beheshti Hospital in Kashan during 2014-2015. The patients were referred to Matini Hospital for the assessment of the auditory brainstem response (ABR; wave latency and interpeak intervals of the waves were also evaluated. According to the serum bilirubin level, the neonates were allocated into two groups; one group had a serum bilirubin level of 13-20 mg/d and another group had a bilirubin level more than 20 mg/d. Results: From 98 neonates, 26 (26.5% had a bilirubin level more than 20 mg/d and 72 (73.5% had a bilirubin level of 13-20 mg/d. Also, 46.1% of the neonates in the first group (bilirubin20 mg/d can cause an auditory processing disorder in neonates. So, performing ABR for screening and early detection of bilirubin toxicity can be recommended as a necessary audiologic intervention in all cases of severe neonatal hyperbilirubinemia.

  18. Brain dynamics of distractibility: interaction between top-down and bottom-up mechanisms of auditory attention.

    Science.gov (United States)

    Bidet-Caulet, Aurélie; Bottemanne, Laure; Fonteneau, Clara; Giard, Marie-Hélène; Bertrand, Olivier

    2015-05-01

    Attention improves the processing of specific information while other stimuli are disregarded. A good balance between bottom-up (attentional capture by unexpected salient stimuli) and top-down (selection of relevant information) mechanisms is crucial to be both task-efficient and aware of our environment. Only few studies have explored how an isolated unexpected task-irrelevant stimulus outside the attention focus can disturb the top-down attention mechanisms necessary to the good performance of the ongoing task, and how these top-down mechanisms can modulate the bottom-up mechanisms of attentional capture triggered by an unexpected event. We recorded scalp electroencephalography in 18 young adults performing a new paradigm measuring distractibility and assessing both bottom-up and top-down attention mechanisms, at the same time. Increasing task load in top-down attention was found to reduce early processing of the distracting sound, but not bottom-up attentional capture mechanisms nor the behavioral distraction cost in reaction time. Moreover, the impact of bottom-up attentional capture by distracting sounds on target processing was revealed as a delayed latency of the N100 sensory response to target sounds mirroring increased reaction times. These results provide crucial information into how bottom-up and top-down mechanisms dynamically interact and compete in the human brain, i.e. on the precarious balance between voluntary attention and distraction.

  19. Mitochondria modify exercise-induced development of stem cell-derived neurons in the adult brain

    National Research Council Canada - National Science Library

    Steib, Kathrin; Schäffner, Iris; Jagasia, Ravi; Ebert, Birgit; Lie, D Chichung

    2014-01-01

    Neural stem cells in the adult mammalian hippocampus continuously generate new functional neurons, which modify the hippocampal network and significantly contribute to cognitive processes and mood regulation...

  20. Suppression of spikes during posttetanic hyperpolarization in auditory neurons: the role of temperature, Ih currents, and the Na+-K+-ATPase pump

    OpenAIRE

    Kim, Jun Hee; von Gersdorff, Henrique

    2012-01-01

    In vivo recordings from postsynaptic neurons in the medial nucleus of the trapezoid body (MNTB), an auditory brain stem nucleus, show that acoustic stimulation produces a burst of spikes followed by a period of hyperpolarization and suppressed spiking activity. The underlying mechanism for this hyperpolarization and reduced spiking is unknown. Furthermore, the mechanisms that control excitability and resting membrane potential are not fully determined for these MNTB neurons. In this study we ...

  1. Induction of Perivascular Neural Stem Cells and Possible Contribution to Neurogenesis Following Transient Brain Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Nakata, Masayo; Nakagomi, Takayuki; Maeda, Mitsuyo; Nakano-Doi, Akiko; Momota, Yoshihiro; Matsuyama, Tomohiro

    2017-04-01

    Recent therapeutic advances have increased the likelihood of recanalizing the obstructed brain arteries in patients with stroke. Therefore, it is important to understand the fate of neural cells under transient ischemia/reperfusion injury. Accumulating evidence shows that neurogenesis occurs in perivascular regions following brain injury, although the precise mechanism and origin of these newborn neurons under transient ischemia/reperfusion injury remain unclear. Using a mouse model of transient brain ischemia/reperfusion injury, we found that neural stem cells (NSCs) develop within injured areas. This induction of NSCs following ischemia/reperfusion injury was observed even in response to nonlethal ischemia, although massive numbers of NSCs were induced by lethal ischemia. Immunohistochemical and immunoelectron microscopic studies indicated that platelet-derived growth factor receptor beta-positive (PDGFRβ+) pericytes within injured areas following nonlethal ischemia began to express the NSC marker nestin as early as 3 days after transient ischemia/reperfusion. Some PDGFRβ+ pericytes expressed the immature neuronal marker doublecortin at day 7. These findings indicate that brain pericytes are a potential source of the perivascular NSCs that generate neuronal cells under lethal and nonlethal ischemic conditions following transient ischemia/reperfusion. Thus, brain pericytes might be a target for neurogenesis mediation in patients with nonlethal and lethal ischemia following transient ischemia/reperfusion injury.

  2. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Directory of Open Access Journals (Sweden)

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  3. Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix japonica). Anterogradely biocytin method.

    Science.gov (United States)

    Sugita, S; Fujikake, N; Sugahara, K; Fujiwara, K; Wada, N

    1996-05-01

    Efferents from the optic tectum to the brain stem in the Japanese quail (Coturnix japonica) were studied with the anterogradely biocytin method. After injection of biocytin into the ipsilateral optic tectum, labeled terminals were seen in the rotund nucleus (Rt), neuropil part of the ventral lateral geniculate nucleus (GLnv), principal part of the dorsal lateral geniculate nucleus, lateral part of the dorsolateral thalamic nucleus, triangular nucleus (T), superficial parvocellular nucleus (SPC), pretectal nucleus, pretectal area (PA), subpretectal nucleus, central gray matter (GC), isthimo optic nucleus (ION), magnocellular and parvocellular parts of the isthimo nuclei (Imc and Ipc), semilunar nucleus (SLu), lateral and medial pontine nuclei and reticular formation (FRM) of the medulla, ipsilaterally. Labeled fibers were seen in the septomesencephalic tract nucleus, FRM, interstitio-paraetecto-subpraetectal nucleus, and the dorsal and ventral tectoreticular tracts (TRd and TRv). In the contralateral brain stem, labeled terminals were seen in the Rt, T. FRM, PA and paramedian nucleus. The contralateral terminals were remarkably fewer than those of the ipsilateral side. The present findings of the labeled terminals of the SPC and the GC at the level of the mesencephalic nucleus of the trigeminal nerve (MnT), and the topographic projection from optic tectum to the Rt in the thalamus, were original observations in the avian. The labeled terminals in the GLnv, Ipc, Imc and ION showed topographical projections from the optic tectum. Pathways to the contralateral brain stem were via the commissure posterior, ventral supraoptic decussation, and the predorsal bundle. The present results suggest that tectofugal impulses in the quail relate to various functions with special relation to the function of the GC at the level of the MnT as well as a visual function.

  4. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...... potentials. Deltamethrin transiently increased the frequency of the respiratory rhythm. Inspiratory potentials in hypoglossal motoneurons were decreased in amplitude and increased in duration. In conclusion, deltamethrin perturbs the respiratory output from the hypoglossal nucleus through postsynaptic...... actions on hypoglossal motoneurons and by affecting the inspiratory synaptic drive....

  5. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jang

    2011-01-01

    Full Text Available This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (<.05. MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

  6. [Auditory fatigue].

    Science.gov (United States)

    Sanjuán Juaristi, Julio; Sanjuán Martínez-Conde, Mar

    2015-01-01

    Given the relevance of possible hearing losses due to sound overloads and the short list of references of objective procedures for their study, we provide a technique that gives precise data about the audiometric profile and recruitment factor. Our objectives were to determine peripheral fatigue, through the cochlear microphonic response to sound pressure overload stimuli, as well as to measure recovery time, establishing parameters for differentiation with regard to current psychoacoustic and clinical studies. We used specific instruments for the study of cochlear microphonic response, plus a function generator that provided us with stimuli of different intensities and harmonic components. In Wistar rats, we first measured the normal microphonic response and then the effect of auditory fatigue on it. Using a 60dB pure tone acoustic stimulation, we obtained a microphonic response at 20dB. We then caused fatigue with 100dB of the same frequency, reaching a loss of approximately 11dB after 15minutes; after that, the deterioration slowed and did not exceed 15dB. By means of complex random tone maskers or white noise, no fatigue was caused to the sensory receptors, not even at levels of 100dB and over an hour of overstimulation. No fatigue was observed in terms of sensory receptors. Deterioration of peripheral perception through intense overstimulation may be due to biochemical changes of desensitisation due to exhaustion. Auditory fatigue in subjective clinical trials presumably affects supracochlear sections. The auditory fatigue tests found are not in line with those obtained subjectively in clinical and psychoacoustic trials. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  7. Atypical brain lateralisation in the auditory cortex and language performance in 3- to 7-year-old children with high-functioning autism spectrum disorder: a child-customised magnetoencephalography (MEG) study.

    Science.gov (United States)

    Yoshimura, Yuko; Kikuchi, Mitsuru; Shitamichi, Kiyomi; Ueno, Sanae; Munesue, Toshio; Ono, Yasuki; Tsubokawa, Tsunehisa; Haruta, Yasuhiro; Oi, Manabu; Niida, Yo; Remijn, Gerard B; Takahashi, Tsutomu; Suzuki, Michio; Higashida, Haruhiro; Minabe, Yoshio

    2013-10-08

    significant predictor of shorter P50m latency in the right hemisphere. Using a child-customised MEG device, we studied the P50m component that was evoked through binaural human voice stimuli in young ASD and TD children to examine differences in auditory cortex function that are associated with language development. Our results suggest that there is atypical brain function in the auditory cortex in young children with ASD, regardless of language development.

  8. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution. © 2015. Published by The Company of Biologists Ltd.

  9. Long-term recovery from hippocampal-related behavioral and biochemical abnormalities induced by noise exposure during brain development. Evaluation of auditory pathway integrity.

    Science.gov (United States)

    Uran, S L; Gómez-Casati, M E; Guelman, L R

    2014-10-01

    Sound is an important part of man's contact with the environment and has served as critical means for survival throughout his evolution. As a result of exposure to noise, physiological functions such as those involving structures of the auditory and non-auditory systems might be damaged. We have previously reported that noise-exposed developing rats elicited hippocampal-related histological, biochemical and behavioral changes. However, no data about the time lapse of these changes were reported. Moreover, measurements of auditory pathway function were not performed in exposed animals. Therefore, with the present work, we aim to test the onset and the persistence of the different extra-auditory abnormalities observed in noise-exposed rats and to evaluate auditory pathway integrity. Male Wistar rats of 15 days were exposed to moderate noise levels (95-97 dB SPL, 2 h a day) during one day (acute noise exposure, ANE) or during 15 days (sub-acute noise exposure, SANE). Hippocampal biochemical determinations as well as short (ST) and long term (LT) behavioral assessments were performed. In addition, histological and functional evaluations of the auditory pathway were carried out in exposed animals. Our results show that hippocampal-related behavioral and biochemical changes (impairments in habituation, recognition and associative memories as well as distortion of anxiety-related behavior, decreases in reactive oxygen species (ROS) levels and increases in antioxidant enzymes activities) induced by noise exposure were almost completely restored by PND 90. In addition, auditory evaluation shows that increased cochlear thresholds observed in exposed rats were re-established at PND 90, although with a remarkable supra-threshold amplitude reduction. These data suggest that noise-induced hippocampal and auditory-related alterations are mostly transient and that the effects of noise on the hippocampus might be, at least in part, mediated by the damage on the auditory pathway

  10. A Bayesian Account of Vocal Adaptation to Pitch-Shifted Auditory Feedback.

    Directory of Open Access Journals (Sweden)

    Richard H R Hahnloser

    Full Text Available Motor systems are highly adaptive. Both birds and humans compensate for synthetically induced shifts in the pitch (fundamental frequency of auditory feedback stemming from their vocalizations. Pitch-shift compensation is partial in the sense that large shifts lead to smaller relative compensatory adjustments of vocal pitch than small shifts. Also, compensation is larger in subjects with high motor variability. To formulate a mechanistic description of these findings, we adapt a Bayesian model of error relevance. We assume that vocal-auditory feedback loops in the brain cope optimally with known sensory and motor variability. Based on measurements of motor variability, optimal compensatory responses in our model provide accurate fits to published experimental data. Optimal compensation correctly predicts sensory acuity, which has been estimated in psychophysical experiments as just-noticeable pitch differences. Our model extends the utility of Bayesian approaches to adaptive vocal behaviors.

  11. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Directory of Open Access Journals (Sweden)

    Daria Namestnikova

    Full Text Available In vivo tracking of transplanted mesenchymal stem cells (MSCs migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  12. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Science.gov (United States)

    Namestnikova, Daria; Gubskiy, Ilya; Kholodenko, Irina; Melnikov, Pavel; Sukhinich, Kirill; Gabashvili, Anna; Vishnevskiy, Daniil; Soloveva, Anastasia; Abakumov, Maxim; Vakhrushev, Igor; Lupatov, Alexei; Chekhonin, Vladimir; Gubsky, Leonid; Yarygin, Konstantin

    2017-01-01

    In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO) particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  13. Auditory Hallucination

    Directory of Open Access Journals (Sweden)

    MohammadReza Rajabi

    2003-09-01

    Full Text Available Auditory Hallucination or Paracusia is a form of hallucination that involves perceiving sounds without auditory stimulus. A common is hearing one or more talking voices which is associated with psychotic disorders such as schizophrenia or mania. Hallucination, itself, is the most common feature of perceiving the wrong stimulus or to the better word perception of the absence stimulus. Here we will discuss four definitions of hallucinations:1.Perceiving of a stimulus without the presence of any subject; 2. hallucination proper which are the wrong perceptions that are not the falsification of real perception, Although manifest as a new subject and happen along with and synchronously with a real perception;3. hallucination is an out-of-body perception which has no accordance with a real subjectIn a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid, substantial, and located in external objective space. We are going to discuss it in details here.

  14. Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells

    OpenAIRE

    Martín, V.; Sanchez-Sanchez, A M; Herrera, F.; Gomez-Manzano, C; Fueyo, J; Alvarez-Vega, M A; Antolín, I; Rodriguez, C.

    2013-01-01

    Background: Current evidence indicates that a stem cell-like sub-population within malignant glioblastomas, that overexpress members of the adenosine triphosphate-binding cassette (ABC) family transporters, is responsible for multidrug resistance and tumour relapse. Eradication of the brain tumour stem cell (BTSC) compartment is therefore essential to achieve a stable and long-lasting remission. Methods: Melatonin actions were analysed by viability cell assays, flow cytometry, quantitative PC...

  15. Activation of RARα, RARγ, or RXRα Increases Barrier Tightness in Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells.

    Science.gov (United States)

    Stebbins, Matthew J; Lippmann, Ethan S; Faubion, Madeline G; Daneman, Richard; Palecek, Sean P; Shusta, Eric V

    2017-09-28

    The blood-brain barrier (BBB) is critical to central nervous system (CNS) health. Brain microvascular endothelial cells (BMECs) are often used as in vitro BBB models for studying BBB dysfunction and therapeutic screening applications. Human pluripotent stem cells (hPSCs) can be differentiated to cells having key BMEC barrier and transporter properties, offering a renewable, scalable source of human BMECs. hPSC-derived BMECs have previously been shown to respond to all-trans retinoic acid (RA), and the goal of this study was to identify the stages at which differentiating human induced pluripotent stem cells (iPSCs) respond to activation of RA receptors (RARs) to impart BBB phenotypes. Here the authors identified that RA application to iPSC-derived BMECs at days 6-8 of differentiation led to a substantial elevation in transendothelial electrical resistance and induction of VE-cadherin expression. Specific RAR agonists identified RARα, RARγ, and RXRα as receptors capable of inducing barrier phenotypes. Moreover, RAR/RXRα costimulation elevated VE-cadherin expression and improved barrier fidelity to levels that recapitulated the effects of RA. This study elucidates the roles of RA signaling in iPSC-derived BMEC differentiation, and identifies directed agonist approaches that can improve BMEC fidelity for drug screening studies while also distinguishing potential nuclear receptor targets to explore in BBB dysfunction and therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Heterotopically transplanted CVO neural stem cells generate neurons and migrate with SVZ cells in the adult mouse brain.

    Science.gov (United States)

    Bennett, Lori B; Cai, Jingli; Enikolopov, Grigori; Iacovitti, Lorraine

    2010-05-07

    Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ (Bennett et al.). The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU(+) cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  18. Human skin-derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain.

    Science.gov (United States)

    Belicchi, Marzia; Pisati, Federica; Lopa, Raffaella; Porretti, Laura; Fortunato, Francesco; Sironi, Manuela; Scalamogna, Mario; Parati, Eugenio A; Bresolin, Nereo; Torrente, Yvan

    2004-08-15

    Recent evidence indicates that neural stem cell properties can be found among a mammalian skin-derived multipotent population. A major barrier in the further characterization of the human skin-derived neural progenitors is the inability to isolate this population based on expression of cell surface markers. Our work has been devoted to purified human skin-derived stem cells that are capable of neural differentiation, based on the presence or absence of the AC133 cell surface marker. The enriched skin-derived AC133(+) cells express the CD34 and Thy-1 antigens. These cells cultured in a growth medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) proliferate, forming spheres, and differentiate in vitro into neurons, astrocytes, and rarely into oligodendrocytes. Single cells from sphere cultures initiated from human purified AC133(+) cells were replated as single cells and were able to generate new spheres, demonstrating the self-renewing ability of these stem cell populations. Brain engraftment of cells obtained from human purified AC133(+)-derived spheres generated different neural phenotypes: immature neurons and a most abundant population of well differentiated astrocytes. The AC133-derived astrocytes assumed perivascular locations in the frontal cortex. No donor-derived oligodendrocytes were found in the transplanted mouse brains. Several donor small, rounded cells that expressed endothelial markers were found close to the host vessel and near the subventricular zone. Thus, mammalian skin AC133-derived cells behave as a multipotent population with the capacity to differentiate into neural lineages in vitro and, prevalently, endothelium and astrocytes in vivo, demonstrating the great plasticity of these cells and suggesting potential clinical application. Copyright 2004 Wiley-Liss, Inc.

  19. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

    Science.gov (United States)

    Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L; Berg, Andrew R; Cinkornpumin, Jessica; Lowry, William E; Segura, Tatiana; Carmichael, S Thomas

    2017-02-01

    This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

  20. Persistent facial myokymia: a rare pathognomic physical sign of intrinsic brain-stem lesions: report of 2 cases and review of literature.

    Directory of Open Access Journals (Sweden)

    Sharma R

    1992-01-01

    Full Text Available Characteristically continuous facial myokymia is a pathognomonic, exceedingly rare physical sign of intrinsic brain-stem lesions e.g. multiple sclerosis (where the myokymia lasts only for a few months, pontine glioma (where it is unremitting for years. The physiopathogenesis is unclear. Electromyographic patterns are characteristic. Therapy and prognosis are related to the basic aetio-pathological process. Only two out of 132 cases of intrinsic brain-stem lesions in the department of Neurosurgery, Seth G.s. Medical College, Bombay over a period of 3 decades, exemplify its rarity. These two cases are reported here and the relevant literature is reviewed.

  1. Auditory memory function in expert chess players

    OpenAIRE

    Fattahi, Fariba; Geshani, Ahmad; Jafari, Zahra; Jalaie, Shohreh; Salman Mahini, Mona

    2015-01-01

    Background: Chess is a game that involves many aspects of high level cognition such as memory, attention, focus and problem solving. Long term practice of chess can improve cognition performances and behavioral skills. Auditory memory, as a kind of memory, can be influenced by strengthening processes following long term chess playing like other behavioral skills because of common processing pathways in the brain. The purpose of this study was to evaluate the auditory memory function of expert...

  2. Auditory Neural Prostheses – A Window to the Future

    Directory of Open Access Journals (Sweden)

    Mohan Kameshwaran

    2015-06-01

    or absent on both sides and hence, a cochlear implant (CI would be inef­fective. In such patients, the brainstem implant bypasses the damaged / absent cochlear nerves and directly stimulates the cochlear nucleus in the brainstem.  The auditory midbrain implant (AMI has been designed for stimulation of the auditory midbrain, particularly the central nucleus of inferior colliculus (ICC. It is used especially in patients with large neurofibromatosis type 2 (NF2 wherein tumor induced damage to the brain­stem/cochlear nucleus often co-exists. The efficacy and safety of auditory neural prostheses is well proven. Advancements in technology will enhance the benefit provided by these prostheses.  Hearing loss is one of the commonest congenital anomalies to affect children world-over. The incidence of congenital hearing loss is more pronounced in developing countries like the Indian sub-continent, especially with the problems of consanguinity. Hearing loss is a double tragedy, as it leads to not only deafness but also language deprivation. However, hearing loss is the only truly remediable handicap, due to remarkable advances in biomedical engineering and surgical techniques. Auditory neural prostheses help to augment or restore hearing by integration of an external circuitry with the peripheral hearing apparatus and the central circuitry of the brain. A cochlear implant (CI is a surgically implantable device that helps restore hearing in patients with severe-profound hearing loss, unresponsive to amplification by conventional hearing aids. CIs are electronic devices designed to detect mechanical sound energy and convert it into electrical signals that can be delivered to the coch­lear nerve, bypassing the damaged hair cells of the coch­lea. The only true prerequisite is an intact auditory nerve. The emphasis is on implantation as early as possible to maximize speech understanding and perception. Bilateral CI has significant benefits which include improved speech

  3. Magnetic Resonance Imaging of Ferumoxytol-Labeled Human Mesenchymal Stem Cells in the Mouse Brain.

    Science.gov (United States)

    Lee, Na Kyung; Kim, Hyeong Seop; Yoo, Dongkyeom; Hwang, Jung Won; Choi, Soo Jin; Oh, Wonil; Chang, Jong Wook; Na, Duk L

    2017-02-01

    The success of stem cell therapy is highly dependent on accurate delivery of stem cells to the target site of interest. Possible ways to track the distribution of MSCs in vivo include the use of reporter genes or nanoparticles. The U.S. Food and Drug Administration (FDA) has approved ferumoxytol (Feraheme® [USA], Rienso® [UK]) as a treatment for iron deficiency anemia. Ferumoxytol is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) that has recently been used to track the fate of transplanted cells using magnetic resonance imaging (MRI). The major objectives of this study were to demonstrate the feasibility of labeling hUCB-MSCs with ferumoxytol and to observe, through MRI, the engraftment of ferumoxytol-labeled human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) delivered via stereotactic injection into the hippocampi of a transgenic mouse model of familial Alzheimer's disease (5XFAD). Ferumoxytol had no toxic effects on the viability or stemness of hUCB-MSCs when assessed in vitro. Through MRI, hypointense signals were discernible at the site where ferumoxytol-labeled human MSCs were injected. Iron-positive areas were also observed in the engrafted hippocampi. The results from this study support the use of nanoparticle labeling to monitor transplanted MSCs in real time as a follow-up for AD stem cell therapy in the clinical field.

  4. An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Canfield, Scott G; Stebbins, Matthew J; Morales, Bethsymarie Soto; Asai, Shusaku W; Vatine, Gad D; Svendsen, Clive N; Palecek, Sean P; Shusta, Eric V

    2017-03-01

    The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human-induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor-like EZ-spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC-derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co-cultured with human iPSC-derived BMECs, the iPSC-derived neurons and astrocytes significantly elevated trans-endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p-glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans. Read the Editorial Highlight for this article on page 843. © 2016 International Society for Neurochemistry.

  5. On-Line Statistical Segmentation of a Non-Speech Auditory Stream in Neonates as Demonstrated by Event-Related Brain Potentials

    Science.gov (United States)

    Kudo, Noriko; Nonaka, Yulri; Mizuno, Noriko; Mizuno, Katsumi; Okanoya, Kazuo

    2011-01-01

    The ability to statistically segment a continuous auditory stream is one of the most important preparations for initiating language learning. Such ability is available to human infants at 8 months of age, as shown by a behavioral measurement. However, behavioral study alone cannot determine how early this ability is available. A recent study using…

  6. Effects of low frequency rTMS treatment on brain networks for inner speech in patients with schizophrenia and auditory verbal hallucinations

    NARCIS (Netherlands)

    Bais, Leonie; Liemburg, Edith; Vercammen, Ans; Bruggeman, Richard; Knegtering, Henderikus; Aleman, Andre

    2017-01-01

    Introduction: Efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) targeting the temporo-parietal junction (TPJ) for the treatment of auditory verbal hallucinations (AVH) remains under debate. We assessed the influence of a 1 Hz rTMS treatment on neural networks involved in a cognitive

  7. c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain.

    Science.gov (United States)

    Wey, Alice; Knoepfler, Paul S

    2010-06-01

    myc genes are associated with a wide variety of human cancers including most types of nervous system tumors. While the mechanisms by which myc overexpression causes tumorigenesis are multifaceted and have yet to be clearly elucidated, they are at least in part related to endogenous myc function in normal cells. Knockout (KO) of either c-myc or N-myc genes in neural stem and precursor cells (NSC) driven by nestin-cre impairs mouse brain growth and mutation of N-myc also causes microcephaly in humans in Feingold Syndrome. To further define myc function in NSC and nervous system development, we created a double KO (DKO) for c- and N-myc using nestin-cre. The DKO mice display profoundly impaired overall brain growth associated with decreased cell cycling and migration of NSC, which are strikingly decreased in number. The DKO brain also exhibits specific changes in gene expression including downregulation of genes involved in protein and nucleotide metabolism, mitosis, and chromatin structure as well as upregulation of genes associated with differentiation. Together these data support a model of nervous system tumorigenesis in which excess myc aberrantly locks in a developmentally active chromatin state characterized by overactive cell cycling, and metabolism as well as blocked differentiation.

  8. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    Science.gov (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  9. Paving the way towards complex blood-brain barrier models using pluripotent stem cells

    DEFF Research Database (Denmark)

    Lauschke, Karin; Frederiksen, Lise; Hall, Vanessa Jane

    2017-01-01

    A tissue with great need to be modelled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types (neurovascular unit (NVU)) that contribute......, it is now possible to produce many cell types from the BBB and even partially recapitulate this complex tissue in vitro. In this review, we summarize the most recent developments in PSC differentiation and modelling of the BBB. We also suggest how patient-specific human induced PSCs could be used to model...

  10. Auditory based neuropsychology in neurosurgery.

    Science.gov (United States)

    Wester, Knut

    2008-04-01

    In this article, an account is given on the author's experience with auditory based neuropsychology in a clinical, neurosurgical setting. The patients that were included in the studies are patients with traumatic or vascular brain lesions, patients undergoing brain surgery to alleviate symptoms of Parkinson's disease, or patients harbouring an intracranial arachnoid cyst affecting the temporal or the frontal lobe. The aims of these investigations were to collect information about the location of cognitive processes in the human brain, or to disclose dyscognition in patients with an arachnoid cyst. All the patients were tested with the DL technique. In addition, the cyst patients were subjected to a number of non-auditory, standard neuropsychological tests, such as Benton Visual Retention Test, Street Gestalt Test, Stroop Test and Trails Test A and B. The neuropsychological tests revealed that arachnoid cysts in general cause dyscognition that also includes auditory processes, and more importantly, that these cognition deficits normalise after surgical removal of the cyst. These observations constitute strong evidence in favour of surgical decompression.

  11. Development and Characterization of a Brain Endothelial Cell Phenotype using Human Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Holst, Bjørn

    be used to investigate drug transport in vitro, and screen candidates for permeation properties. One recent approach is to develop in vitro models of the BBB using human induced pluripotent stem cells (hIPSCs) as described by Stebbins et al. (2015).The aim of the present study was to investigate whether...

  12. Characterization of auditory synaptic inputs to gerbil perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Vibhakar C Kotak

    2015-08-01

    Full Text Available The representation of acoustic cues involves regions downstream from the auditory cortex (ACx. One such area, the perirhinal cortex (PRh, processes sensory signals containing mnemonic information. Therefore, our goal was to assess whether PRh receives auditory inputs from the auditory thalamus (MG and ACx in an auditory thalamocortical brain slice preparation and characterize these afferent-driven synaptic properties. When the MG or ACx was electrically stimulated, synaptic responses were recorded from the PRh neurons. Blockade of GABA-A receptors dramatically increased the amplitude of evoked excitatory potentials. Stimulation of the MG or ACx also evoked calcium transients in most PRh neurons. Separately, when fluoro ruby was injected in ACx in vivo, anterogradely labeled axons and terminals were observed in the PRh. Collectively, these data show that the PRh integrates auditory information from the MG and ACx and that auditory driven inhibition dominates the postsynaptic responses in a non-sensory cortical region downstream from the auditory cortex.

  13. Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse

    NARCIS (Netherlands)

    Donega, Vanessa; Nijboer, Cora H.A.; Van Velthoven, Cindy T J; Youssef, Sameh A.; De Bruin, Alain; Van Bel, Frank; Kavelaars, Annemieke; Heijnen, Cobi J.; Nijboer, CHA

    2015-01-01

    Background:For clinical translation, we assessed whether intranasal mesenchymal stem cell (MSC) treatment after hypoxia-ischemia (HI) induces neoplasia in the brain or periphery at 14 mo. Furthermore, the long-term effects of MSCs on behavior and lesion size were determined.Method:HI was induced in

  14. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

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    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  15. Quiescence and activation of stem and precursor cell populations in the subependymal zone of the mammalian brain are associated with distinct cellular and extracellular matrix signals

    Science.gov (United States)

    The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularize...

  16. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain.

    Science.gov (United States)

    Kosi, Nina; Alić, Ivan; Kolačević, Matea; Vrsaljko, Nina; Jovanov Milošević, Nataša; Sobol, Margarita; Philimonenko, Anatoly; Hozák, Pavel; Gajović, Srećko; Pochet, Roland; Mitrečić, Dinko

    2015-02-09

    The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  18. Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    with the aim of extending the classification of inspiratory neurons to include analysis of active membrane properties. 2. The slice generated a regular rhythmic motor output recorded as burst of action potentials on a XII nerve root with a peak to peak time of 11.5 +/- 3.4 s and a duration of 483 +/- 54 ms......1. The electrophysiological properties of inspiratory neurons were studied in a rhythmically active thick-slice preparation of the newborn mouse brain stem maintained in vitro. Whole cell patch recordings were performed from 60 inspiratory neurons within the rostral ventrolateral part of the slice...... (means +/- SD, n = 50). Based on the electroresponsive properties and membrane potential trajectories throughout the respiratory cycle, three types of inspiratory neurons could be distinguished. 3. Type-1 neurons were spiking in the interval between the inspiratory potentials (n = 9) or silent...

  19. Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

    Science.gov (United States)

    Singhi, Pratibha; Saini, Arushi Gahlot; Sankhyan, Naveen; Gupta, Pankaj; Vyas, Sameer

    2015-01-01

    A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. © The Author(s) 2014.

  20. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......, and control of heart beat. Here we show that the rostral compact formation's ambiguus neurons, which control the esophageal phase of swallowing, display calcium-dependent plateau potentials in response to tetanic orthodromic stimulation or current injection. Whole cell recordings were made from visualized...... neurons in the rostral nucleus ambiguus using a slice preparation from the newborn mouse. Biocytin-labeling revealed dendritic trees with pronounced rostrocaudal orientations confined to the nucleus ambiguus, a morphological profile matching that of vagal motoneurons projecting to the esophagus. Single...

  1. Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    Dai Kuang-Yu

    2010-09-01

    Full Text Available Abstract Background Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM because it is the origin of a life-and-death signal that sequentially increases (pro-life and decreases (pro-death to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1 may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1 and nitric oxide synthase I (NOS I/protein kinase G (PKG cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death. Methods We performed cardiovascular, pharmacological, biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of adult male Sprague-Dawley rats. Results Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1α or HIF-1β in RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons manifested insignificant changes during both phases. Furthermore, immunoneutralization of HO-1 or knockdown of ho-1 gene in RVLM blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without affecting the pro-death NOS II/peroxynitrite cascade in RVLM. Conclusions We conclude that transcriptional

  2. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  3. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

    Directory of Open Access Journals (Sweden)

    Lina R. Nih

    2017-02-01

    Full Text Available This article presents data related to the research article “Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain” (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016 [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1 Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2 the use of a design of Experiment (DOE approach (M.W. 2 Weible and T. Chan-Ling, 2007 [2] to select multi-factorial experimental conditions, and (3 Inflammatory response and cell survival after transplantation.

  4. Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation.

    Science.gov (United States)

    Lu, Jiang; Li, Dongsheng; Lu, Kehuan

    2012-07-05

    The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth

  5. Neural stem cell transplantation in an animal model of traumatic brain injury.

    Science.gov (United States)

    Thomaidou, Dimitra

    2014-01-01

    The central nervous system (CNS) can be damaged by a wide range of conditions resulting in loss of specific populations of neurons and/or glial cells and in the development of defined psychiatric or neurological symptoms of varying severity. As the CNS has limited inherent capacity to regenerate lost tissue and self-repair, the development of therapeutic strategies for the treatment of CNS insults remains a serious scientific challenge with potential important clinical applications. In this context, strategies involving transplantation of specific cell populations, such as stem cells and neural stem cells (NSCs), to replace damaged cells offers an opportunity for the development of cell-based therapies. Along these lines, in this review we describe a protocol which involves transplantation of NPCs, genetically engineered to overexpress the neurogenic molecule Cend1 and have thus the potency to differentiate with higher frequency towards the neuronal lineage in a rodent model of stab wound cortical injury.

  6. Optimization of the magnetic labeling of human neural stem cells and MRI visualization in the hemiparkinsonian rat brain.

    Science.gov (United States)

    Ramos-Gómez, Milagros; Seiz, Emma G; Martínez-Serrano, Alberto

    2015-03-05

    Magnetic resonance imaging is the ideal modality for non-invasive in vivo cell tracking allowing for longitudinal studies over time. Cells labeled with superparamagnetic iron oxide nanoparticles have been shown to induce sufficient contrast for in vivo magnetic resonance imaging enabling the in vivo analysis of the final location of the transplanted cells. For magnetic nanoparticles to be useful, a high internalization efficiency of the particles is required without compromising cell function, as well as validation of the magnetic nanoparticles behaviour inside the cells. In this work, we report the development, optimization and validation of an efficient procedure to label human neural stem cells with commercial nanoparticles in the absence of transfection agents. Magnetic nanoparticles used here do not affect cell viability, cell morphology, cell differentiation or cell cycle dynamics. Moreover, human neural stem cells progeny labeled with magnetic nanoparticles are easily and non-invasively detected long time after transplantation in a rat model of Parkinson's disease (up to 5 months post-grafting) by magnetic resonance imaging. These findings support the use of commercial MNPs to track cells for short- and mid-term periods after transplantation for studies of brain cell replacement therapy. Nevertheless, long-term MR images should be interpreted with caution due to the possibility that some MNPs may be expelled from the transplanted cells and internalized by host microglial cells.

  7. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  8. Entrainment to an auditory signal: Is attention involved?

    NARCIS (Netherlands)

    Kunert, R.; Jongman, S.R.

    2017-01-01

    Many natural auditory signals, including music and language, change periodically. The effect of such auditory rhythms on the brain is unclear however. One widely held view, dynamic attending theory, proposes that the attentional system entrains to the rhythm and increases attention at moments of

  9. Auditory memory function in expert chess players.

    Science.gov (United States)

    Fattahi, Fariba; Geshani, Ahmad; Jafari, Zahra; Jalaie, Shohreh; Salman Mahini, Mona

    2015-01-01

    Chess is a game that involves many aspects of high level cognition such as memory, attention, focus and problem solving. Long term practice of chess can improve cognition performances and behavioral skills. Auditory memory, as a kind of memory, can be influenced by strengthening processes following long term chess playing like other behavioral skills because of common processing pathways in the brain. The purpose of this study was to evaluate the auditory memory function of expert chess players using the Persian version of dichotic auditory-verbal memory test. The Persian version of dichotic auditory-verbal memory test was performed for 30 expert chess players aged 20-35 years and 30 non chess players who were matched by different conditions; the participants in both groups were randomly selected. The performance of the two groups was compared by independent samples t-test using SPSS version 21. The mean score of dichotic auditory-verbal memory test between the two groups, expert chess players and non-chess players, revealed a significant difference (p≤ 0.001). The difference between the ears scores for expert chess players (p= 0.023) and non-chess players (p= 0.013) was significant. Gender had no effect on the test results. Auditory memory function in expert chess players was significantly better compared to non-chess players. It seems that increased auditory memory function is related to strengthening cognitive performances due to playing chess for a long time.

  10. Changes in host blood factors and brain glia accompanying the functional recovery after systemic administration of bone marrow stem cells in ischemic stroke rats.

    Science.gov (United States)

    Yang, Ming; Wei, Xiaotao; Li, Jing; Heine, Lynn A; Rosenwasser, Robert; Iacovitti, Lorraine

    2010-01-01

    In this study, we examined the effects of systemic administration of rat or human bone marrow stromal stem cells (MSC) at early and later times following middle cerebral artery occlusion (MCAO) on blood cytokines/growth factors, brain glia, and motor behavior in rats. Rats were tail vein injected with rat (r) and human (h) MSCs at 1 or 7 days post-MCAO. In some rats (N = 4) MSCs isolated from transgenic GFP rats were used to track the migration of cells peripherally and centrally at 2.5 and 28 days. Motor behavior was assessed using the modified Neurological Severity Score/climbing test at various time points before and after MCAO and transplantation. Prior to sacrifice at 1, 7, or 28 days post-MCAO, blood serum was collected for cytokine array analysis. Brains were analyzed for markers of activated microglia (CD11) and reactive astrocytes (GFAP). Administration of either allogeneic (rMSCs) or xenogeneic (hMSCs) stem cells produced a significant recovery of motor behavior after MCAO, with cells delivered at 1 day having greater effect than those at 7 days. Correlated with recovery was an amplification in activated microglia, reactive astrocytes, and new blood vessels in the infarct region, resulting in greater preservation in brain integrity. Concomitantly, expression of blood cytokines/chemokines (IL-13, MMP2, MIP) and growth factors/receptors (VEGF, neuropilin, EPOR, TROY, NGFR, RAGE) were modified following MSC administration. Because only rare GFP-labeled MSCs were observed in the brain, these effects did not depend on the central incorporation of stem cells. The early systemic administration of allogeneic or xenogeneic MSCs soon after experimental stroke produces a structural/functional recovery in the brain which is correlated with an increase in activated brain glia and changes in circulating cytokines and growth factors. Stem cells therefore induce an important neuroprotective and/or regenerative response in the host organism.

  11. Reduced 5-HT(1B) receptor binding in the dorsal brain stem after cognitive behavioural therapy of major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Rück, Christian; Forsberg, Anton; Varrone, Andrea; Lindefors, Nils; Halldin, Christer; Farde, Lars; Lundberg, Johan

    2014-08-30

    Major depression is a significant contributor to the global burden of disease, and its pathophysiology is largely unknown. The serotonin hypothesis is, however, the model with most supporting data, although the details are only worked out to some extent. Recent clinical imaging measurements indeed imply a role in major depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5-hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B receptor binding in the brain of MDD patients before and after psychotherapy. Ten patients with an ongoing untreated moderate depressive episode were examined with positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369, before and after treatment with internet-based cognitive behavioural therapy. All of the patients examined responded to treatment, and 70% were in remission by the time of the second PET measurement. A statistically significant 33% reduction of binding potential (BPND) was found in the dorsal brain stem (DBS) after treatment. No other significant changes in BPND were found. The DBS contains the raphe nuclei, which regulate the serotonin system. This study gives support for the importance of serotonin and the 5-HT1B receptor in the biological response to psychological treatment of MDD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Brain stem audiometry may supply markers for diagnostic and therapeutic control in psychiatry.

    Science.gov (United States)

    Nielzén, Sören; Holmberg, Jens; Sköld, Mia; Nehlstedt, Sara

    2016-10-06

    The purpose of the present study is to try an alternative way of analyzing the ABR (Auditory Brainstem Response). The stimuli were complex sounds (c-ABR) as used in earlier studies. It was further aimed at corroborating earlier findings that this method can discriminate several neuropsychiatric states. Forty healthy control subjects, 26 subjects with the diagnosis schizophrenia (Sz) and 33 with ADHD (Attention deficit hyperactivity disorder) were recruited for the study. The ABRs were recorded. The analysis was based on calculation of areas of significantly group different time spans in the waves. Both latency and amplitude were thereby influential. The spans of differences were quantified for each subject in relation to the total area of the curve which made comparisons balanced. The results showed highly significant differences between the study groups. The results are important for future work on identifying markers for neuropsychiatric clinical use. To reach that goal calls for more extensive studies than this preliminary one. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Reconstructing speech from human auditory cortex.

    Directory of Open Access Journals (Sweden)

    Brian N Pasley

    2012-01-01

    Full Text Available How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex.

  14. Effect of omega-3 on auditory system

    Directory of Open Access Journals (Sweden)

    Vida Rahimi

    2014-01-01

    Full Text Available Background and Aim: Omega-3 fatty acid have structural and biological roles in the body 's various systems . Numerous studies have tried to research about it. Auditory system is affected a s well. The aim of this article was to review the researches about the effect of omega-3 on auditory system.Methods: We searched Medline , Google Scholar, PubMed, Cochrane Library and SID search engines with the "auditory" and "omega-3" keywords and read textbooks about this subject between 19 70 and 20 13.Conclusion: Both excess and deficient amounts of dietary omega-3 fatty acid can cause harmful effects on fetal and infant growth and development of brain and central nervous system esspesially auditory system. It is important to determine the adequate dosage of omega-3.

  15. Middle components of the auditory evoked response in bilateral temporal lobe lesions. Report on a patient with auditory agnosia

    DEFF Research Database (Denmark)

    Parving, A; Salomon, G; Elberling, Claus

    1980-01-01

    An investigation of the middle components of the auditory evoked response (10--50 msec post-stimulus) in a patient with auditory agnosia is reported. Bilateral temporal lobe infarctions were proved by means of brain scintigraphy, CAT scanning, and regional cerebral blood flow measurements. The mi...

  16. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2009-10-01

    conditions is promising ( 1 ) . Furthermore, it has previously 1. Introduction John S. Yu (ed.), Cancer Stem Cells, Methods in Molecular Biology, vol...D, Aucoin R, Blust J, Murry B, Greiter‐ Wilke  A: p75 neurotrophin receptor functions as a survival receptor in brain‐metastatic melanoma cells, J...domains. Nat Biotechnol 23(9): 1126-1136. (39) Colcher D, Pavlinkova G, Beresford G, Booth BJ, Choudhury A, Batra SK (1998) Pharmacokinetics and

  17. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  18. The chicken immediate-early gene ZENK is expressed in the medio-rostral neostriatum/hyperstriatum ventrale, a brain region involved in acoustic imprinting, and is up-regulated after exposure to an auditory stimulus.

    Science.gov (United States)

    Thode, C; Bock, J; Braun, K; Darlison, M G

    2005-01-01

    The immediate-early gene zenk (an acronym for the avian orthologue of the mammalian genes zif-268, egr-1, ngfi-a and krox-24) has been extensively employed, in studies on oscine birds, as a marker of neuronal activity to reveal forebrain structures that are involved in the memory processes associated with the acquisition, perception and production of song. Audition-induced expression of this gene, in brain, has also recently been reported for the domestic chicken (Gallus gallus domesticus) and the Japanese quail (Coturnix coturnix japonica). Whilst the anatomical distribution of zenk expression was described for the quail, corresponding data for the chicken were not reported. We have, therefore, used in situ hybridisation to localise the mRNA that encodes the product of the zenk gene (which we call ZENK) within the brain of the 1-day-old chick. We demonstrate that this transcript is present in a number of forebrain structures including the medio-rostral neostriatum/hyperstriatum ventrale (MNH), a region that has been strongly implicated in auditory imprinting (which is a form of recognition memory), and Field L, the avian analog of the mammalian auditory cortex. Because of this pattern of gene expression, we have compared the level of the ZENK mRNA in chicks that have been subjected to a 30-min acoustic imprinting paradigm and in untrained controls. Our results reveal a significant increase (Pimprinting, which is an established model of juvenile learning. In addition, our results indicate that the ZENK mRNA may be used as a molecular marker for MNH, a region that is difficult to anatomically and histochemically delineate.

  19. Biological and clinical implications of cancer stem cells in primary brain tumors

    Directory of Open Access Journals (Sweden)

    Marcello eMaugeri-Saccà

    2013-01-01

    Full Text Available Despite therapeutic advances, glioblastoma multiforme (GBM remains a lethal disease. The infiltrative nature of this disease and the presence of a cellular population resistant to current medical treatments account for the poor prognosis of these patients. Growing evidence indicates the existence of a fraction of cancer cells sharing the functional properties of adult stem cells, including self-renewal and a greater ability to escape chemo-radiotherapy-induced death stimuli. Therefore, these cells are commonly defined as cancer stem cells (GBM-SCs. The initial GBM-SC concept has been challenged, and refined according to the emerging molecular taxonomy of GBM. This allowed to postulate the existence of multiple CSC types, each one driving a given molecular entity. Furthermore, it is becoming increasingly clear that GBM-SCs thrive through a dynamic and bidirectional interaction with the surrounding microenvironment. In this article, we discuss recent advances in GBM-SC biology, mechanisms through which these cells adapt to hostile conditions, pharmacological strategies for selectively killing GBM-SCs, and how novel CSC-associated endpoints have been investigated in the clinical setting.

  20. Abnormal connectivity between attentional, language and auditory networks in schizophrenia

    NARCIS (Netherlands)

    Liemburg, Edith J.; Vercammen, Ans; Ter Horst, Gert J.; Curcic-Blake, Branislava; Knegtering, Henderikus; Aleman, Andre

    Brain circuits involved in language processing have been suggested to be compromised in patients with schizophrenia. This does not only include regions subserving language production and perception, but also auditory processing and attention. We investigated resting state network connectivity of

  1. Reality of auditory verbal hallucinations.

    Science.gov (United States)

    Raij, Tuukka T; Valkonen-Korhonen, Minna; Holi, Matti; Therman, Sebastian; Lehtonen, Johannes; Hari, Riitta

    2009-11-01

    Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency.

  2. A functional study of EGFR and Notch signaling in brain cancer stem-like cells from glioblastoma multiforme (Ph.d.)

    DEFF Research Database (Denmark)

    Kristoffersen, Karina

    2013-01-01

    for new molecular and cellular targets that can improve the prognosis for GBM patients. One such target is the brain cancer stem-like cells (bCSC) that are believed to be responsible for tumor initiation, progression, treatment resistance and ultimately relapse. bCSC are identified based...... treatment. The overall aim of the present PhD project has been to study the functional role of EGFR and Notch activity in bCSCs stem cell-like features and tumorigenic potential with the purpose of deepen our knowledge about the significance of these pathways in the bCSC population in GBM. By establishing...

  3. Evaluation of 18F-FDG PET and MRI associations in pediatric diffuse intrinsic brain stem glioma: a report from the Pediatric Brain Tumor Consortium.

    Science.gov (United States)

    Zukotynski, Katherine A; Fahey, Frederic H; Kocak, Mehmet; Alavi, Abass; Wong, Terence Z; Treves, S Ted; Shulkin, Barry L; Haas-Kogan, Daphne A; Geyer, Jeffrey R; Vajapeyam, Sridhar; Boyett, James M; Kun, Larry E; Poussaint, Tina Young

    2011-02-01

    The purpose of this study was to assess (18)F-FDG uptake in children with a newly diagnosed diffuse intrinsic brain stem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS), and MRI indices. Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: phase I/II study of gefitinib; PBTC-014: phase I/II study of tipifarnib). Baseline brain (18)F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus between 2 PET experts for intensity and uniformity of tracer uptake. Associations of (18)F-FDG uptake intensity and uniformity with both PFS and OS, as well as associations with tumor MRI indices at baseline (tumor volume on fluid-attenuated inversion recovery, baseline intratumoral enhancement, diffusion and perfusion values), were evaluated. In most of the children, BSG (18)F-FDG uptake was less than gray-matter uptake. Survival was poor, irrespective of intensity of (18)F-FDG uptake, with no association between intensity of (18)F-FDG uptake and PFS or OS. However, hyperintense (18)F-FDG uptake in the tumor, compared with gray matter, suggested poorer survival rates. Patients with (18)F-FDG uptake in 50% or more of the tumor had shorter PFS and OS than did patients with (18)F-FDG uptake in less than 50% of the tumor. There was some evidence that tumors with higher (18)F-FDG uptake were more likely to show enhancement, and when the diffusion ratio was lower, the uniformity of (18)F-FDG uptake appeared higher. Children with BSG for which (18)F-FDG uptake involves at least half the tumor appear to have poorer survival than children with uptake in less than 50% of the tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors, compared with gray matter, suggests decreased survival. Higher (18)F-FDG uptake

  4. Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression.

    Directory of Open Access Journals (Sweden)

    Laura Rota Nodari

    Full Text Available Understanding the physiology of human neural stem cells (hNSCs in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably

  5. Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

    Science.gov (United States)

    Srivastava, Amit K; Bulte, Camille A; Shats, Irina; Walczak, Piotr; Bulte, Jeff W M

    2016-01-01

    Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (ptransplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (pcells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Diagnosing Dyslexia: The Screening of Auditory Laterality.

    Science.gov (United States)

    Johansen, Kjeld

    A study investigated whether a correlation exists between the degree and nature of left-brain laterality and specific reading and spelling difficulties. Subjects, 50 normal readers and 50 reading disabled persons native to the island of Bornholm, had their auditory laterality screened using pure-tone audiometry and dichotic listening. Results…

  7. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.

    Science.gov (United States)

    Haus, Daniel L; López-Velázquez, Luci; Gold, Eric M; Cunningham, Kelly M; Perez, Harvey; Anderson, Aileen J; Cummings, Brian J

    2016-07-01

    Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically cell transplantation. Additionally, human cell engraftment and long-term survival in rodent models of TBI has been difficult to achieve due to host immunorejection of the transplanted human cells, which confounds conclusions pertaining to transplant-mediated behavioral improvement. To overcome these shortfalls, we have developed a novel TBI xenotransplantation model that utilizes immunodeficient athymic nude (ATN) rats as the host recipient for the post-TBI transplantation of human embryonic stem cell (hESC) derived NSCs and have evaluated cognition in these animals at long-term (≥2months) time points post-injury. We report that immunodeficient ATN rats demonstrate hippocampal-dependent spatial memory deficits (Novel Place, Morris Water Maze), but not non-spatial (Novel Object) or emotional/anxiety-related (Elevated Plus Maze, Conditioned Taste Aversion) deficits, at 2-3months post-TBI, confirming that ATN rats recapitulate some of the cognitive deficits found in immunosufficient animal strains. Approximately 9-25% of transplanted hNSCs survived for at least 5months post-transplantation and differentiated into mature neurons (NeuN, 18-38%), astrocytes (GFAP, 13-16%), and oligodendrocytes (Olig2, 11-13%). Furthermore, while this model of TBI (cortical impact) targets primarily cortex and the underlying hippocampus and generates a large lesion cavity, hNSC transplantation facilitated cognitive recovery without affecting either lesion volume or total spared cortical or hippocampal tissue volume. Instead, we

  8. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  9. Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post-Traumatic brain injury.

    Science.gov (United States)

    Ghazale, Hussein; Ramadan, Naify; Mantash, Sara; Zibara, Kazem; El-Sitt, Sally; Darwish, Hala; Chamaa, Farah; Boustany, Rose Mary; Mondello, Stefania; Abou-Kheir, Wassim; Soueid, Jihane; Kobeissy, Firas

    2018-03-15

    Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the subventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA+NSCs treated animals showed decreased levels of 38kDa GFAP-BDP (breakdown product) and 145kDa αII-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior

  10. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

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    Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

    2004-07-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  11. Conceptual priming for realistic auditory scenes and for auditory words.

    Science.gov (United States)

    Frey, Aline; Aramaki, Mitsuko; Besson, Mireille

    2014-02-01

    Two experiments were conducted using both behavioral and Event-Related brain Potentials methods to examine conceptual priming effects for realistic auditory scenes and for auditory words. Prime and target sounds were presented in four stimulus combinations: Sound-Sound, Word-Sound, Sound-Word and Word-Word. Within each combination, targets were conceptually related to the prime, unrelated or ambiguous. In Experiment 1, participants were asked to judge whether the primes and targets fit together (explicit task) and in Experiment 2 they had to decide whether the target was typical or ambiguous (implicit task). In both experiments and in the four stimulus combinations, reaction times and/or error rates were longer/higher and the N400 component was larger to ambiguous targets than to conceptually related targets, thereby pointing to a common conceptual system for processing auditory scenes and linguistic stimuli in both explicit and implicit tasks. However, fine-grained analyses also revealed some differences between experiments and conditions in scalp topography and duration of the priming effects possibly reflecting differences in the integration of perceptual and cognitive attributes of linguistic and nonlinguistic sounds. These results have clear implications for the building-up of virtual environments that need to convey meaning without words. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Multicystic encephalomalacia associated with symmetrical necrotizing brain stem lesions in an infant: a case report.

    Science.gov (United States)

    Simonati, A; Laverda, A M; Rizzuto, N

    1986-01-01

    The simultaneous occurrence of multicystic encephalomalacia of the cerebral hemispheres, and symmetric necrotizing lesions of diencephalic and infratentorial structures is described in a 15 month-old infant. The baby developed clonic jerks of four limbs a few hours after delivery. She attained no developmental milestones, and remained bed-ridden with hypertonic posture until her death. Multicystic cavities of the cerebral hemispheres were well evident at CT scan when she was 7 months old. The topographic distributions of the different pathological pictures are described; their relationship to the regional properties of the developing brain are commented upon. Etiological aspects of this case are discussed according to present knowledge of the pathophysiological mechanisms leading either to multiple cyst formation or to necrotizing lesions.

  13. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain

    Directory of Open Access Journals (Sweden)

    Anna-Lena Hallmann

    2016-05-01

    Full Text Available Reprogramming technology enables the production of neural progenitor cells (NPCs from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  14. Over-expression of brain-derived neurotrophic factor in mesenchymal stem cells transfected with recombinant lentivirus BDNF gene.

    Science.gov (United States)

    Zhang, X; Zhu, J; Zhang, K; Liu, T; Zhang, Z

    2016-12-30

    This study was aimed at investigating the expression of brain-derived neurotrophic factor (BDNF) in mesenchymal stem cells (MSCs) modified with recombinant lentivirus bearing BDNF gene. Lentivirus vectors bearing BDNF gene were constructed. MSCs were isolated from rats and cultured. The lentiviral vectors containing BDNF gene were transfected into the MSCs, and BDNF gene and protein expressions were monitored with enhanced green fluorescent protein (EGFP). RT-PCR and Western blot were used to measure gene and protein expressions, respectibvely in MSCs, MSCs-EGFP and MSCs-EGFP-BDNF groups. Green fluorescence assay confirmed successful transfection of BDNF gene recombinant lentivirus into MSCs. RT-PCR and Western blot revealed that BDNF gene and protein expressions in the MSCs-EGFP-BDNF group were significantly higher than that in MSCs group and MSCs-EGFP group. There were no statistically significant differences in gene expression between MSCs and MSCs-EGFP groups. MSCs can over-express BDNF when transfected with recombinant lentivirus bearing BDNF gene.

  15. [A case of primary brain-stem injury recovered from persistent vegetative state after L-dopa administration].

    Science.gov (United States)

    Matsuda, W; Sugimoto, K; Sato, N; Watanabe, T; Yanaka, K; Matsumura, A; Nose, T

    1999-12-01

    A 51-year-old male was transferred to our hospital just after traffic accident. On admission, the patient was comatose (Glasgow Coma Scale of 6) and showed a left hemiparesis with a left oculomotor nerve palsy. Computed tomography demonstrated a traumatic subarachnoid hemorrhage without mass lesion. Magnetic resonance imaging showed high intensity lesions on the left dorsolateral midbrain and the right cerebral peduncle. The distribution of lesions implied diffuse axonal injury involving dopaminergic systems such as the substantia nigra and the ventral tegmental area. After several months of conservative management, the patient showed no recovery and was diagnosed as persistent vegetable state. The administration of L-dopa was then started and the patient showed remarkable neurological improvement. Therefore the patient's neurological status was thought to be modified with primary brain stem injury and accompanying traumatic Parkinson's syndrome. It is important to understand "pseudo" persistent vegetative state in the management of patients showing prolonged consciousness disturbance. L-dopa should be considered as the drugs of pharmacological intervention for the patients of masked parkinsonism behind "pseudo" persistent vegetative state whose dopaminergic systems might have been damaged.

  16. The Neuroprotective Effects of Muscle-Derived Stem Cells via Brain-Derived Neurotrophic Factor in Spinal Cord Injury Model

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    Donghe Han

    2017-01-01

    Full Text Available Muscle-derived stem cells (MDSCs possess multipotent differentiation and self-renewal capacities; however, the effects and mechanism in neuron injury remain unclear. The aim of this study was to investigate the effects of MDSCs on neuron secondary injury, oxidative stress-induced apoptosis. An in vivo study showed the Basso, Beattie, and Bresnahan (BBB score and number of neurons significantly increased after MDSCs’ transplantation in spinal cord injury (SCI rats. An in vitro study demonstrated that MDSCs attenuated neuron apoptosis, and the expression of antioxidants was upregulated as well as the ratio of Bcl-2 and Bax in the MNT (MDSCs cocultured with injured neurons group compared with the NT (injured neurons group. Both LC3II/LC3I and β-catenin were enhanced in the MNT group, while XAV939 (a β-catenin inhibitor decreased the expression of nuclear erythroid-related factor 2 (Nrf2 and LC3II/LC3I. Moreover, MDSCs became NSE- (neuron-specific enolase- positive neuron-like cells with brain-derived neurotrophic factor (BDNF treatment. The correlation analysis indicated that there was a significant relation between the level of BDNF and neuron injury. These findings suggest that MDSCs may protect the spinal cord from injury by inhibiting apoptosis and replacing injured neurons, and the increased BDNF and β-catenin could contribute to MDSCs’ effects.

  17. Brain responses and looking behaviour during audiovisual speech integration in infants predict auditory speech comprehension in the second year of life.

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    Elena V Kushnerenko

    2013-07-01

    Full Text Available The use of visual cues during the processing of audiovisual speech is known to be less efficient in children and adults with language difficulties and difficulties are known to be more prevalent in children from low-income populations. In the present study, we followed an economically diverse group of thirty-seven infants longitudinally from 6-9 months to 14-16 months of age. We used eye-tracking to examine whether individual differences in visual attention during audiovisual processing of speech in 6 to 9 month old infants, particularly when processing congruent and incongruent auditory and visual speech cues, might be indicative of their later language development. Twenty-two of these 6-9 month old infants also participated in an event-related potential (ERP audiovisual task within the same experimental session. Language development was then followed-up at the age of 14-16 months, using two measures of language development, the Preschool Language Scale (PLS and the Oxford Communicative Development Inventory (CDI. The results show that those infants who were less efficient in auditory speech processing at the age of 6-9 months had lower receptive language scores at 14-16 months. A correlational analysis revealed that the pattern of face scanning and ERP responses to audio-visually incongruent stimuli at 6-9 months were both significantly associated with language development at 14-16 months. These findings add to the understanding of individual differences in neural signatures of audiovisual processing and associated looking behaviour in infants.

  18. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  19. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Haejin Lee

    Full Text Available Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%, APC-CC1+ oligodendrocytes (∼28%, and GFAP+ astrocytes (∼8%. Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest

  20. Neural Entrainment to Auditory Imagery of Rhythms

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    Haruki Okawa

    2017-10-01

    Full Text Available A method of reconstructing perceived or imagined music by analyzing brain activity has not yet been established. As a first step toward developing such a method, we aimed to reconstruct the imagery of rhythm, which is one element of music. It has been reported that a periodic electroencephalogram (EEG response is elicited while a human imagines a binary or ternary meter on a musical beat. However, it is not clear whether or not brain activity synchronizes with fully imagined beat and meter without auditory stimuli. To investigate neural entrainment to imagined rhythm during auditory imagery of beat and meter, we recorded EEG while nine participants (eight males and one female imagined three types of rhythm without auditory stimuli but with visual timing, and then we analyzed the amplitude spectra of the EEG. We also recorded EEG while the participants only gazed at the visual timing as a control condition to confirm the visual effect. Furthermore, we derived features of the EEG using canonical correlation analysis (CCA and conducted an experiment to individually classify the three types of imagined rhythm from the EEG. The results showed that classification accuracies exceeded the chance level in all participants. These results suggest that auditory imagery of meter elicits a periodic EEG response that changes at the imagined beat and meter frequency even in the fully imagined conditions. This study represents the first step toward the realization of a method for reconstructing the imagined music from brain activity.

  1. Avaliação comportamental do processamento auditivo em indivíduos pós - traumatismo cranioencefálico: estudo piloto Behavioral auditory processing evaluation after traumatic brain injury: pilot study

    Directory of Open Access Journals (Sweden)

    Renata Beatriz Fernandes Santos

    2013-01-01

    Full Text Available OBJETIVO: verificar o desempenho de indivíduos pós-traumatismo cranioencefálico em testes comportamentais para avaliação do processamento auditivo. MÉTODO: participaram da pesquisa 10 indivíduos audiologicamente normais com histórico de trauma craniano. Foram submetidos a: audiometria tonal liminar, logoaudiometria, medidas de imitância acústica (timpanometria e pesquisa dos reflexos acústicos e avaliação comportamental do processamento auditivo (Testes de Localização Sonora, Memória Sequencial Verbal, Memória Sequencial Não Verbal, Padrão de Duração, Dicótico Consoante-Vogal, Dicótico de Dissílabos Alternados, Identificação de Sentenças Sintéticas com mensagem competitiva, Identificação de Intervalo Aleatório, Índice Percentual de Reconhecimento de Fala com gravação, Fala com Ruído Branco. RESULTADOS: o teste de Padrão de Duração indicou o teste com o maior número de alteração (60%. O teste com a média mais satisfatória foi o Índice Percentual de Reconhecimento de Fala com gravação (93% e a média menos satisfatória relacionou-se ao teste Dicótico Consoante-Vogal, com 40,56%. As inversões (70% representaram a tendência de erros no Dicótico de Dissílabos Alternados mais frequente. O processo gnósico do tipo decodificação foi o mais predominante (100%, seguido da organização (90%, não verbal (60%, codificação-perda gradual de memória (20%. Não houve alteração no processo gnósico de codificação-integração. CONCLUSÃO: os indivíduos pós-traumatismo cranioencefálico apresentam transtorno do processamento auditivo de diferentes graus, envolvendo os processos gnósicos de decodificação e organização.PURPOSE: to characterize the performance of individuals after traumatic brain injury in behavioral tests to evaluate auditory processing. METHOD: the participants of this research were 10 individuals with normal hearing with traumatic brain injury. They were submitted to: pure tone

  2. [The utilization of brain plasticity by cochlear implants : Molecular and cellular changes due to electrical intracochlear stimulation].

    Science.gov (United States)

    Rosskothen-Kuhl, N; Illing, R-B

    2015-02-01

    During pre- and postnatal development, a high level of growth-associated protein 43 (Gap43) is expressed in the brain. This neuron-specific protein is expressed in somata, axons, and growth cones and plays a key role in neurite outgrowth and synaptogenesis. With maturation of the brain, Gap43 is down-regulated by most neurons, except in brain areas such as the hippocampal CA3 region or the binaural auditory regions lateral superior olive (LSO) and central inferior colliculus (CIC). This study investigated how changes in sensory activity levels and patterns can modulate the adult plasticity response. To study the effect of sensory activity on adult Gap43 expression, mRNA and protein levels were determined in LSO and CIC of hearing-experienced rats, unilaterally and bilaterally deafened rats, or rats unilaterally stimulated by a cochlear implant (CI). Unilateral hearing loss of an adult auditory system causes asymmetrical expression of Gap43 mRNA between ipsi- and contralateral LSOs or CICs of the brain stem. While the mRNA level rose on the contralateral side of the LSO, CIC neurons increased their gap43 transcription ipsilaterally compared to the control level (pstimulation resulted in a bilaterally symmetric but increased gap43 transcription. Our data indicate that Gap43 is not only a marker for neuronal growth and synaptogenesis, but also reflects modified patterns of synaptic activities on auditory neurons. Thus, unilateral deafness directly results in an asymmetrical adaptation of the gap43 transcription between both sides of the auditory brain stem. This can be prevented by simple-patterned stimulation of the auditory nerve via a CI.

  3. Simultanagnosia does not affect processes of auditory Gestalt perception.

    Science.gov (United States)

    Rennig, Johannes; Bleyer, Anna Lena; Karnath, Hans-Otto

    2017-05-01

    Simultanagnosia is a neuropsychological deficit of higher visual processes caused by temporo-parietal brain damage. It is characterized by a specific failure of recognition of a global visual Gestalt, like a visual scene or complex objects, consisting of local elements. In this study we investigated to what extend this deficit should be understood as a deficit related to specifically the visual domain or whether it should be seen as defective Gestalt processing per se. To examine if simultanagnosia occurs across sensory domains, we designed several auditory experiments sharing typical characteristics of visual tasks that are known to be particularly demanding for patients suffering from simultanagnosia. We also included control tasks for auditory working memory deficits and for auditory extinction. We tested four simultanagnosia patients who suffered from severe symptoms in the visual domain. Two of them indeed showed significant impairments in recognition of simultaneously presented sounds. However, the same two patients also suffered from severe auditory working memory deficits and from symptoms comparable to auditory extinction, both sufficiently explaining the impairments in simultaneous auditory perception. We thus conclude that deficits in auditory Gestalt perception do not appear to be characteristic for simultanagnosia and that the human brain obviously uses independent mechanisms for visual and for auditory Gestalt perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Biological impact of auditory expertise across the life span: musicians as a model of auditory learning

    Science.gov (United States)

    Strait, Dana L.; Kraus, Nina

    2013-01-01

    Experience-dependent characteristics of auditory function, especially with regard to speech-evoked auditory neurophysiology, have garnered increasing attention in recent years. This interest stems from both pragmatic and theoretical concerns as it bears implications for the prevention and remediation of language-based learning impairment in addition to providing insight into mechanisms engendering experience-dependent changes in human sensory function. Musicians provide an attractive model for studying the experience-dependency of auditory processing in humans due to their distinctive neural enhancements compared to nonmusicians. We have only recently begun to address whether these enhancements are observable early in life, during the initial years of music training when the auditory system is under rapid development, as well as later in life, after the onset of the aging process. Here we review neural enhancements in musically trained individuals across the life span in the context of cellular mechanisms that underlie learning, identified in animal models. Musicians’ subcortical physiologic enhancements are interpreted according to a cognitive framework for auditory learning, providing a model by which to study mechanisms of experience-dependent changes in auditory function in humans. PMID:23988583

  5. BAER - brainstem auditory evoked response

    Science.gov (United States)

    ... auditory potentials; Brainstem auditory evoked potentials; Evoked response audiometry; Auditory brainstem response; ABR; BAEP ... Normal results vary. Results will depend on the person and the instruments used to perform the test.

  6. Auditory Processing Disorder (For Parents)

    Science.gov (United States)

    ... role. Auditory cohesion problems: This is when higher-level listening tasks are difficult. Auditory cohesion skills — drawing inferences from conversations, understanding riddles, or comprehending verbal math problems — require heightened auditory processing and language levels. ...

  7. Intravenous xenotransplantation of human placental mesenchymal stem cells to rats: comparative analysis of homing in rat brain in two models of experimental ischemic stroke.

    Science.gov (United States)

    Kholodenko, I V; Yarygin, K N; Gubsky, L V; Konieva, A A; Tairova, R T; Povarova, O V; Kholodenko, R V; Burunova, V V; Yarygin, V N; Skvortsova, V I

    2012-11-01

    Mesenchymal stem cells from human placenta obtained after term natural delivery were cultured and labeled with vital dye Dil of magnetic fluorescing microparticles. The labeled cells were transplanted intravenously to rats with occlusion of the median cerebral artery. Penetration of cells through the brain-blood barrier and their distribution in the brain of experimental animals were studied on serial cryostat sections. Two models of cerebral artery occlusion associated with different traumatic consequences were used. The efficiency of crossing the blood-brain barrier by transplanted cells, the number of mesenchymal cells attaining the ischemic focus and neurogenic zones, and the time of death of transplanted cells largely depended on the degree and nature of injury to the central nervous system, which should be taken into account when planning the experiments for evaluation of the effects of cell therapy on the models of neurological diseases and in clinical studies in the field of regenerative neurology.

  8. Severe auditory processing disorder secondary to viral meningoencephalitis.

    Science.gov (United States)

    Pillion, Joseph P; Shiffler, Dorothy E; Hoon, Alexander H; Lin, Doris D M

    2014-06-01

    To describe auditory function in an individual with bilateral damage to the temporal and parietal cortex. Case report. A previously healthy 17-year old male is described who sustained extensive cortical injury following an episode of viral meningoencephalitis. He developed status epilepticus and required intubation and multiple anticonvulsants. Serial brain MRIs showed bilateral temporoparietal signal changes reflecting extensive damage to language areas and the first transverse gyrus of Heschl on both sides. The patient was referred for assessment of auditory processing but was so severely impaired in speech processing that he was unable to complete any formal tests of his speech processing abilities. Audiological assessment utilizing objective measures of auditory function established the presence of normal peripheral auditory function and illustrates the importance of the use of objective measures of auditory function in patients with injuries to the auditory cortex. Use of objective measures of auditory function is essential in establishing the presence of normal peripheral auditory function in individuals with cortical damage who may not be able to cooperate sufficiently for assessment utilizing behavioral measures of auditory function.

  9. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mimata, Yoshikuni; Sato, Kotaro; Suzuki, Yoshiaki [Iwate Prefectural Chubu Hospital, Department of Orthopaedic Surgery, Kitakami (Japan); Murakami, Hideki [Iwate Medical University, Department of Orthopaedic Surgery, School of Medicine, Morioka (Japan)

    2014-01-15

    Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important. (orig.)

  10. The effect of simvastatin treatment on proliferation and differentiation of neural stem cells after traumatic brain injury.

    Science.gov (United States)

    Xie, Chuncheng; Cong, Damin; Wang, Xiujuan; Wang, Yuehua; Liang, Hongsheng; Zhang, Xiangtong; Huang, Qi

    2015-03-30

    To study the effect of simvastatin on neurological functional recovery after traumatic brain injuries (TBI) and the possible molecular mechanisms, we evaluated simvastatin-induced proliferation and differentiation of neural stem cells (NSCs) in vitro and in vivo and possible involvement of Notch-1 signaling in this process. Adult Wistar rats were randomly divided into three groups (n=28 for each): sham group, saline-treated group and simvastatin-treated group. Simvastatin was given orally at a dose of 1mg/kg/day starting at day 1 after TBI. At 1, 3, 7, 14, 21, 28, and 35 days after simvastatin treatment, functional outcome was measured using modified neurological severity scores (mNSS). Immunofluorescence of nestin was used to identify neurogenesis of NSCs in injured area of TBI rats. Western blot was applied to detect the expression level of Notch-1 protein in TBI rats with simvastatin. Immunostaining showed a significant increase in the number of nestin-positive cells in injured area of the simvastatin-treated group compared to that of the saline-treated group (p<0.05). In in vitro experiment, simvastatin induced enhanced proliferation and neurogenesis of cultured NSCs and elevated Notch-1 protein expression. Co-incubation of γ-secretase inhibitor, an inhibitor of Notch-1 pathway, with simvastatin abolished its neurorestoration effect. Most importantly, the simvastatin-treated group had significantly decreased mNSS at day 35 after TBI compared with the saline-treated group (p<0.05). Simvastatin treatment enhanced neurological functional recovery after TBI possibly via activation of Notch signaling and increasing neurogenesis in the injured area. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Temporal prediction errors in visual and auditory cortices.

    Science.gov (United States)

    Lee, Hweeling; Noppeney, Uta

    2014-04-14

    To form a coherent percept of the environment, the brain needs to bind sensory signals emanating from a common source, but to segregate those from different sources [1]. Temporal correlations and synchrony act as prominent cues for multisensory integration [2-4], but the neural mechanisms by which such cues are identified remain unclear. Predictive coding suggests that the brain iteratively optimizes an internal model of its environment by minimizing the errors between its predictions and the sensory inputs [5,6]. This model enables the brain to predict the temporal evolution of natural audiovisual inputs and their statistical (for example, temporal) relationship. A prediction of this theory is that asynchronous audiovisual signals violating the model's predictions induce an error signal that depends on the directionality of the audiovisual asynchrony. As the visual system generates the dominant temporal predictions for visual leading asynchrony, the delayed auditory inputs are expected to generate a prediction error signal in the auditory system (and vice versa for auditory leading asynchrony). Using functional magnetic resonance imaging (fMRI), we measured participants' brain responses to synchronous, visual leading and auditory leading movies of speech, sinewave speech or music. In line with predictive coding, auditory leading asynchrony elicited a prediction error in visual cortices and visual leading asynchrony in auditory cortices. Our results reveal predictive coding as a generic mechanism to temporally bind signals from multiple senses into a coherent percept. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Resizing Auditory Communities

    DEFF Research Database (Denmark)

    Kreutzfeldt, Jacob

    2012-01-01

    Heard through the ears of the Canadian composer and music teacher R. Murray Schafer the ideal auditory community had the shape of a village. Schafer’s work with the World Soundscape Project in the 70s represent an attempt to interpret contemporary environments through musical and auditory...

  13. Brain evoked potential use in a physical medicine and rehabilitation setting.

    Science.gov (United States)

    Rappaport, M; Hopkins, K; Hall, K; Belleza, T; Berrol, S

    1978-01-01

    The objective of this effort was to explore the use of evoked potential (EP) procedure on a head injury unit in a Department of Physical Medicine and Rehabilitation. The method employed both auditory and visual stimulation presented bilaterally to various patients. Recordings of the brain's responses to such stimulation were obtained. Results permitted evaluation of brain stem, subcortical and cortical functioning, ipsilaterally, contralaterally, and bilaterally. EP data provided useful information for patient assessment and rehabilitation planning for head injured patients--particularly for those who were unable to cooperate in their own examination.

  14. Anatomical Pathways for Auditory Memory in Primates

    Directory of Open Access Journals (Sweden)

    Monica Munoz-Lopez

    2010-10-01

    Full Text Available Episodic memory or the ability to store context-rich information about everyday events depends on the hippocampal formation (entorhinal cortex, subiculum, presubiculum, parasubiculum, hippocampus proper, and dentate gyrus. A substantial amount of behavioral-lesion and anatomical studies have contributed to our understanding of the organization of how visual stimuli are retained in episodic memory. However, whether auditory memory is organized similarly is still unclear. One hypothesis is that, like the ‘visual ventral stream’ for which the connections of the inferior temporal gyrus with the perirhinal cortex are necessary for visual recognition in monkeys, direct connections between the auditory association areas of the superior temporal gyrus and the hippocampal formation and with the parahippocampal region (temporal pole, perhirinal, and posterior parahippocampal cortices might also underlie recognition memory for sounds. Alternatively, the anatomical organization of memory could be different in audition. This alternative ‘indirect stream’ hypothesis posits that, unlike the visual association cortex, the majority of auditory association cortex makes one or more synapses in intermediate, polymodal areas, where they may integrate information from other sensory modalities, before reaching the medial temporal memory system. This review considers anatomical studies that can support either one or both hypotheses – focusing on anatomical studies on the primate brain that have reported not only direct auditory association connections with medial temporal areas, but, importantly, also possible indirect pathways for auditory information to reach the medial temporal lobe memory system.

  15. The Harmonic Organization of Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Xiaoqin eWang

    2013-12-01

    Full Text Available A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds.

  16. The harmonic organization of auditory cortex

    Science.gov (United States)

    Wang, Xiaoqin

    2013-01-01

    A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds. PMID:24381544

  17. Effects of Caffeine on Auditory Brainstem Response

    Directory of Open Access Journals (Sweden)

    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.

  18. Functional imaging of the central auditory system using PET

    NARCIS (Netherlands)

    Ruytjens, L.; Willemsen, A. T. M.; Van Dijk, P.; Wit, H. P.; Albers, F. W. J.

    2006-01-01

    In the last few decades functional neuroimaging tools have emerged to study the function of the human brain in vivo. These techniques have increased the knowledge of how the brain processes stimuli of different sensory modalities, including auditory processing. Positron emission tomography (PET) has

  19. Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells.

    Science.gov (United States)

    Razavi, Shahnaz; Razavi, Mohamad Reza; Zarkesh Esfahani, Hamid; Kazemi, Mohammad; Mostafavi, Fatemeh Sadat

    2013-08-01

    Adipose derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) may be equally beneficial in treating neurodegenerative diseases. However, ADSCs have practical advantages. In this study, we aimed to induce neurotrophic factors secreting cells in human ADSCs. Then, we compared the level of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion in neurotrophic factors secreting cells from human adipose and bone marrow-derived stem cells. Isolated human ADSCs and BMSCs were induced to neurotrophic factor (NTF)-secreting cells. The levels of expression and secretion of BDNF and CTNF of induced cells were assessed using immunocytochemical, Real-Time polymerase chain reaction, and enzyme linked immunosorbent assay (ELISA). The level of BDNF significantly increased in both the induced mesenchymal stem cells (MSCs) relative to ADSCs and the BMSCs (P < 0.01). Moreover, ELISA analysis showed that the release of BDNF in the induced BMSCs was almost twofold more than the induced ADSCs. Overall, NTF-secreting factor cells derived BMSCs and ADSCs could secret a range of different growth factors. Therefore, the variation in neurotrophic factors of different induced MSC populations suggest the possible beneficial effect of each specific kind of neurotrophic factor secreting cells for the treatment of a particular neurodegenerative disease. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  20. Can adult neural stem cells create new brains? Plasticity in the adult mammalian neurogenic niches: realities and expectations in the era of regenerative biology.

    Science.gov (United States)

    Kazanis, Ilias

    2012-02-01

    Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.

  1. Auditory-motor learning influences auditory memory for music.

    Science.gov (United States)

    Brown, Rachel M; Palmer, Caroline

    2012-05-01

    In two experiments, we investigated how auditory-motor learning influences performers' memory for music. Skilled pianists learned novel melodies in four conditions: auditory only (listening), motor only (performing without sound), strongly coupled auditory-motor (normal performance), and weakly coupled auditory-motor (performing along with auditory recordings). Pianists' recognition of the learned melodies was better following auditory-only or auditory-motor (weakly coupled and strongly coupled) learning than following motor-only learning, and better following strongly coupled auditory-motor learning than following auditory-only learning. Auditory and motor imagery abilities modulated the learning effects: Pianists with high auditory imagery scores had better recognition following motor-only learning, suggesting that auditory imagery compensated for missing auditory feedback at the learning stage. Experiment 2 replicated the findings of Experiment 1 with melodies that contained greater variation in acoustic features. Melodies that were slower and less variable in tempo and intensity were remembered better following weakly coupled auditory-motor learning. These findings suggest that motor learning can aid performers' auditory recognition of music beyond auditory learning alone, and that motor learning is influenced by individual abilities in mental imagery and by variation in acoustic features.

  2. Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

    Science.gov (United States)

    Al-Ahmad, Abraham J

    2017-10-01

    Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

  3. In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Kokubu, Yasuhiro; Yamaguchi, Tomoko; Kawabata, Kenji

    2017-04-29

    Brain-derived microvascular endothelial cells (BMECs), which play a central role in blood brain barrier (BBB), can be used for the evaluation of drug transport into the brain. Although human BMEC cell lines have already been reported, they lack original properties such as barrier integrity. Pluripotent stem cells (PSCs) can be used for various applications such as regenerative therapy, drug screening, and pathological study. In the recent study, an induction method of BMECs from PSCs has been established, making it possible to more precisely study the in vitro human BBB function. Here, using induced pluripotent stem (iPS) cell-derived BMECs, we examined the effects of oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) on BBB permeability. OGD disrupted the barrier function, and the dysfunction was rapidly restored by re-supply of the oxygen and glucose. Interestingly, TNF-α, which is known to be secreted from astrocytes and microglia in the cerebral ischemia, prevented the restoration of OGD-induced barrier dysfunction in an apoptosis-independent manner. Thus, we could establish the in vitro BBB disease model that mimics the cerebral ischemia by using iPS cell-derived BMECs. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. High-dose Chemotherapy With Autologous Stem Cell Rescue in Saudi Children Less Than 3 Years of Age With Embryonal Brain Tumors.

    Science.gov (United States)

    Alsultan, Abdulrahman; Alharbi, Musa; Al-Dandan, Sadeq; Bayoumi, Yasser; Alharbi, Talal; Alsudairy, Reem; Alomari, Ali; Aljamaan, Khalid; Musleh, Othman; Alharbi, Qasim; Jarrar, Mohammed

    2015-04-01

    High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) has been used in children under the age of 3 years with embryonal brain tumors to avoid or delay the use of radiation. We reviewed the medical records of 10 Saudi children less than 3 years of age with embryonal brain tumors who underwent HDC/ASCR. All 10 patients underwent surgical resection followed by 3 to 5 cycles of induction chemotherapy and 1 to 3 cycles of HDC/ASCR using carboplatin and thiotepa. Isotretinoin was used as a maintenance therapy in 4 patients. Five patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumors, 1 had an embryonal tumor with abundant neuropil and true rosettes, and 1 had pineoblastoma. The median age of the patients was 1.9 years. A total of 19 HDC/ASCR procedures were performed. Radiotherapy (RT) was administered to 5 patients after HDC/ASCR and as a salvage therapy in 1 patient. The progression-free survival rate was 50% at 1 year and at 2 years, with a median follow-up of 24 months. All 5 patients with medulloblastoma are still alive without evidence of disease, but the other patients died secondary to tumor progression. This experience suggests that strategies combining myeloablative chemotherapy and autologous stem cell rescue appear to be feasible for children with embryonal brain tumors in the Middle East.

  5. fMRI of the auditory system: understanding the neural basis of auditory gestalt.

    Science.gov (United States)

    Di Salle, Francesco; Esposito, Fabrizio; Scarabino, Tommaso; Formisano, Elia; Marciano, Elio; Saulino, Claudio; Cirillo, Sossio; Elefante, Raffaele; Scheffler, Klaus; Seifritz, Erich

    2003-12-01

    Functional magnetic resonance imaging (fMRI) has rapidly become the most widely used imaging method for studying brain functions in humans. This is a result of its extreme flexibility of use and of the astonishingly detailed spatial and temporal information it provides. Nevertheless, until very recently, the study of the auditory system has progressed at a considerably slower pace compared to other functional systems. Several factors have limited fMRI research in the auditory field, including some intrinsic features of auditory functional anatomy and some peculiar interactions between fMRI technique and audition. A well known difficulty arises from the high intensity acoustic noise produced by gradient switching in echo-planar imaging (EPI), as well as in other fMRI sequences more similar to conventional MR sequences. The acoustic noise interacts in an unpredictable way with the experimental stimuli both from a perceptual point of view and in the evoked hemodynamics. To overcome this problem, different approaches have been proposed recently that generally require careful tailoring of the experimental design and the fMRI methodology to the specific requirements posed by the auditory research. The novel methodological approaches can make the fMRI exploration of auditory processing much easier and more reliable, and thus may permit filling the gap with other fields of neuroscience research. As a result, some fundamental neural underpinnings of audition are being clarified, and the way sound stimuli are integrated in the auditory gestalt are beginning to be understood.

  6. Lateralization of auditory-cortex functions.

    Science.gov (United States)

    Tervaniemi, Mari; Hugdahl, Kenneth

    2003-12-01

    In the present review, we summarize the most recent findings and current views about the structural and functional basis of human brain lateralization in the auditory modality. Main emphasis is given to hemodynamic and electromagnetic data of healthy adult participants with regard to music- vs. speech-sound encoding. Moreover, a selective set of behavioral dichotic-listening (DL) results and clinical findings (e.g., schizophrenia, dyslexia) are included. It is shown that human brain has a strong predisposition to process speech sounds in the left and music sounds in the right auditory cortex in the temporal lobe. Up to great extent, an auditory area located at the posterior end of the temporal lobe (called planum temporale [PT]) underlies this functional asymmetry. However, the predisposition is not bound to informational sound content but to rapid temporal information more common in speech than in music sounds. Finally, we obtain evidence for the vulnerability of the functional specialization of sound processing. These altered forms of lateralization may be caused by top-down and bottom-up effects inter- and intraindividually In other words, relatively small changes in acoustic sound features or in their familiarity may modify the degree in which the left vs. right auditory areas contribute to sound encoding.

  7. Auditory Neuroimaging with fMRI and PET

    Science.gov (United States)

    Talavage, Thomas M.; Gonzalez-Castillo, Javier; Scott, Sophie K.

    2013-01-01

    For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging. PMID:24076424

  8. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

    Science.gov (United States)

    Gondi, Vinai; Pugh, Stephanie L; Tome, Wolfgang A; Caine, Chip; Corn, Ben; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey N; Konski, Andre A; Bauman, Glenn S; Shah, Sunjay; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa; Mehta, Minesh P

    2014-12-01

    Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P memory and QOL as compared with historical series. © 2014 by American Society of Clinical Oncology.

  9. [Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea Pigs].

    Science.gov (United States)

    Liu, Shu-Yun; Deng, Li-Qiang; Yang, Ye; Yin, Ze-Deng

    2017-04-25

    To observe the expression of catechol-O-methyltransferase (COMT) in inferior colliculus and auditory cortex of guinea pigs with age-related hearing loss(AHL) induced by D-galactose, so as to explore the possible mechanism of electroacupuncture(EA) underlying preventing AHL. Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group(n=10 in each group), and ten 18-month-old guinea pigs were allocated as elderly group. The AHL model was established by subcutaneous injection of D-galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for 15 min in the EA group while modeling, once daily for 6 weeks. After treatment, the latency of auditory brainstem response(ABR) Ⅲ wave was measured by a brain-stem evoked potentiometer. The expressions of COMT in the inferior colliculus and auditory cortex were detected by Western blot. Compared with the control group, the latencies of ABR Ⅲ wave were significantly prolonged and the expressions of COMT in the inferior colliculus and auditory cortex were significantly decreased in the model group and the elderly group(P<0.05). After the treatment, the latency of ABR Ⅲ wave was significantly shortened and the expressions of COMT in the inferior colliculus and auditory cortex were significantly increased in the EA group in comparison with the model group (P<0.05). EA at "Yifeng" (SJ 17) and "Tinggong" (SI 19) can improve the hearing of age-related deafness in guinea pigs, which may contribute to its effect in up-regulating the expression of COMT in the inferior colliculus and auditory cortex.

  10. Isolation of Neural Stem and Progenitor Cells from the Adult Brain and Live Imaging of Their Cell Cycle with the FUCCI System.

    Science.gov (United States)

    Chicheportiche, Alexandra; Ruat, Martial; Boussin, François D; Daynac, Mathieu

    2018-01-01

    Neural stem cells (NSCs) enter quiescence in early embryonic stages to create a reservoir of dormant NSCs able to enter proliferation and produce neuronal precursors in the adult mammalian brain. Various approaches of fluorescent-activated cell sorting (FACS) have emerged to allow the distinction between quiescent NSCs (qNSCs), their activated counterpart (aNSCs), and the resulting progeny. In this article, we review two FACS techniques that can be used alternatively. We also show that their association with transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice allows an unprecedented overlook on the cell cycle dynamics of adult NSCs.

  11. Auditory Integration Training

    Directory of Open Access Journals (Sweden)

    Zahra Jafari

    2002-07-01

    Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depressin, and hyperacute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of The Sound of a Moracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.

  12. Review: Auditory Integration Training

    Directory of Open Access Journals (Sweden)

    Zahra Ja'fari

    2003-01-01

    Full Text Available Auditory integration training (AIT is a hearing enhancement training process for sensory input anomalies found in individuals with autism, attention deficit hyperactive disorder, dyslexia, hyperactivity, learning disability, language impairments, pervasive developmental disorder, central auditory processing disorder, attention deficit disorder, depression, and hyper acute hearing. AIT, recently introduced in the United States, and has received much notice of late following the release of the sound of a miracle, by Annabel Stehli. In her book, Mrs. Stehli describes before and after auditory integration training experiences with her daughter, who was diagnosed at age four as having autism.

  13. Auditory cortex involvement in emotional learning and memory.

    Science.gov (United States)

    Grosso, A; Cambiaghi, M; Concina, G; Sacco, T; Sacchetti, B

    2015-07-23

    Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  15. Processing Temporal Modulations in Binaural and Monaural Auditory Stimuli by Neurons in the Inferior Colliculus and Auditory Cortex

    OpenAIRE

    Fitzpatrick, Douglas C.; Roberts, Jason M.; Kuwada, Shigeyuki; Kim, Duck O.; Filipovic, Blagoje

    2009-01-01

    Processing dynamic changes in the stimulus stream is a major task for sensory systems. In the auditory system, an increase in the temporal integration window between the inferior colliculus (IC) and auditory cortex is well known for monaural signals such as amplitude modulation, but a similar increase with binaural signals has not been demonstrated. To examine the limits of binaural temporal processing at these brain levels, we used the binaural beat stimulus, which causes a fluctuating inter...

  16. Postnatal Development of Brain-Derived Neurotrophic Factor (BDNF) and Tyrosine Protein Kinase B (TrkB) Receptor Immunoreactivity in Multiple Brain Stem Respiratory-Related Nuclei of the Rat

    Science.gov (United States)

    Liu, Qiuli; Wong-Riley, Margaret T.T.

    2013-01-01

    Previously, we found a transient imbalance between suppressed excitation and enhanced inhibition in the respiratory network of the rat around postnatal days (P) 12–13, a critical period when the hypoxic ventilatory response is at its weakest. The mechanism underlying the imbalance is poorly understood. Brain-derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors are known to potentiate glutamatergic and attenuate gamma-aminobutyric acid (GABA)ergic neurotransmission, and BDNF is essential for respiratory development. We hypothesized that the excitation-inhibition imbalance during the critical period stemmed from a reduced expression of BDNF and TrkB at that time within respiratory-related nuclei of the brain stem. An in-depth, semiquantitative immunohistochemical study was undertaken in seven respiratory-related brain stem nuclei and one nonrespiratory nucleus in P0–21 rats. The results indicate that the expressions of BDNF and TrkB: 1) in the pre-Bötzinger complex, nucleus ambiguus, commissural and ventrolateral subnuclei of solitary tract nucleus, and retrotrapezoid nucleus/parafacial respiratory group were significantly reduced at P12, but returned to P11 levels by P14; 2) in the lateral paragigantocellular nucleus and parapyramidal region were increased from P0 to P7, but were strikingly reduced at P10 and plateaued thereafter; and 3) in the nonrespiratory cuneate nucleus showed a gentle plateau throughout the first 3 post-natal weeks, with only a slight decline of BDNF expression after P11. Thus, the significant downregulation of both BDNF and TrkB in respiratory-related nuclei during the critical period may form the basis of, or at least contribute to, the inhibitory-excitatory imbalance within the respiratory network during this time. PMID:22678720

  17. BALDEY: A database of auditory lexical decisions.

    Science.gov (United States)

    Ernestus, Mirjam; Cutler, Anne

    2015-01-01

    In an auditory lexical decision experiment, 5541 spoken content words and pseudowords were presented to 20 native speakers of Dutch. The words vary in phonological make-up and in number of syllables and stress pattern, and are further representative of the native Dutch vocabulary in that most are morphologically complex, comprising two stems or one stem plus derivational and inflectional suffixes, with inflections representing both regular and irregular paradigms; the pseudowords were matched in these respects to the real words. The BALDEY ("biggest auditory lexical decision experiment yet") data file includes response times and accuracy rates, with for each item morphological information plus phonological and acoustic information derived from automatic phonemic segmentation of the stimuli. Two initial analyses illustrate how this data set can be used. First, we discuss several measures of the point at which a word has no further neighbours and compare the degree to which each measure predicts our lexical decision response outcomes. Second, we investigate how well four different measures of frequency of occurrence (from written corpora, spoken corpora, subtitles, and frequency ratings by 75 participants) predict the same outcomes. These analyses motivate general conclusions about the auditory lexical decision task. The (publicly available) BALDEY database lends itself to many further analyses.

  18. Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice

    Science.gov (United States)

    Barzilay, R; Ben-Zur, T; Sadan, O; Bren, Z; Taler, M; Lev, N; Tarasenko, I; Uzan, R; Gil-Ad, I; Melamed, E; Weizman, A; Offen, D

    2011-01-01

    Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg−1 daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder. PMID:22832353

  19. Aktiverende Undervisning i auditorier

    DEFF Research Database (Denmark)

    Parus, Judith

    Workshop om erfaringer og brug af aktiverende metoder i undervisning i auditorier og på store hold. Hvilke metoder har fungeret godt og hvilke dårligt ? Hvilke overvejelser skal man gøre sig.......Workshop om erfaringer og brug af aktiverende metoder i undervisning i auditorier og på store hold. Hvilke metoder har fungeret godt og hvilke dårligt ? Hvilke overvejelser skal man gøre sig....

  20. Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases.

    Science.gov (United States)

    Kanojia, Deepak; Balyasnikova, Irina V; Morshed, Ramin A; Frank, Richard T; Yu, Dou; Zhang, Lingjiao; Spencer, Drew A; Kim, Julius W; Han, Yu; Yu, Dihua; Ahmed, Atique U; Aboody, Karen S; Lesniak, Maciej S

    2015-10-01

    The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation. © 2015 AlphaMed Press.