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Sample records for frontal cortex role

  1. Role of Frontal Cortex in Attentional Capture by Singleton Distractors

    Science.gov (United States)

    de Fockert, Jan W.; Theeuwes, Jan

    2012-01-01

    The role of frontal cortex in selective attention to visual distractors was examined in an attentional capture task in which participants searched for a unique shape in the presence or absence of an additional colour singleton distractor. The presence of the additional singleton was associated with slower behavioural responses to the shape target,…

  2. The role of the frontal cortex in memory: an investigation of the Von Restorff effect

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    Elhalal, Anat; Davelaar, Eddy J.; Usher, Marius

    2014-01-01

    Evidence from neuropsychology and neuroimaging indicate that the pre-frontal cortex (PFC) plays an important role in human memory. Although frontal patients are able to form new memories, these memories appear qualitatively different from those of controls by lacking distinctiveness. Neuroimaging studies of memory indicate activation in the PFC under deep encoding conditions, and under conditions of semantic elaboration. Based on these results, we hypothesize that the PFC enhances memory by extracting differences and commonalities in the studied material. To test this hypothesis, we carried out an experimental investigation to test the relationship between the PFC-dependent factors and semantic factors associated with common and specific features of words. These experiments were performed using Free-Recall of word lists with healthy adults, exploiting the correlation between PFC function and fluid intelligence. As predicted, a correlation was found between fluid intelligence and the Von-Restorff effect (better memory for semantic isolates, e.g., isolate “cat” within category members of “fruit”). Moreover, memory for the semantic isolate was found to depend on the isolate's serial position. The isolate item tends to be recalled first, in comparison to non-isolates, suggesting that the process interacts with short term memory. These results are captured within a computational model of free recall, which includes a PFC mechanism that is sensitive to both commonality and distinctiveness, sustaining a trade-off between the two. PMID:25018721

  3. A causal role for posterior medial frontal cortex in choice-induced preference change.

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    Izuma, Keise; Akula, Shyam; Murayama, Kou; Wu, Daw-An; Iacoboni, Marco; Adolphs, Ralph

    2015-02-25

    After a person chooses between two items, preference for the chosen item will increase and preference for the unchosen item will decrease because of the choice made. In other words, we tend to justify or rationalize our past behavior by changing our attitude. This phenomenon of choice-induced preference change has been traditionally explained by cognitive dissonance theory. Choosing something that is disliked or not choosing something that is liked are both cognitively inconsistent and, to reduce this inconsistency, people tend to change their subsequently stated preference in accordance with their past choices. Previously, human neuroimaging studies identified posterior medial frontal cortex (pMFC) as a key brain region involved in cognitive dissonance. However, it remains unknown whether the pMFC plays a causal role in inducing preference change after cognitive dissonance. Here, we demonstrate that 25 min, 1 Hz repetitive transcranial magnetic stimulation applied over the pMFC significantly reduces choice-induced preference change compared with sham stimulation or control stimulation over a different brain region, demonstrating a causal role for the pMFC. Copyright © 2015 the authors 0270-6474/15/353598-09$15.00/0.

  4. Preconditioning of Spatial and Auditory Cues: Roles of the Hippocampus, Frontal Cortex, and Cue-Directed Attention

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    Andrew C. Talk

    2016-12-01

    Full Text Available Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity.

  5. Generating predictions: lesion evidence on the role of left inferior frontal cortex in rapid syntactic analysis.

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    Jakuszeit, Maria; Kotz, Sonja A; Hasting, Anna S

    2013-01-01

    A well-documented phenomenon in event-related electroencephalography (EEG) and magnetoencephalography (MEG) studies on language processing is that syntactic violations of different types elicit negativities as early as 100 msec after the violation point. Recently, these responses have been associated with activations in or very close to sensory cortices, suggesting the involvement of basic sensory mechanisms in the detection of syntactic violations. The present study investigated whether intact auditory cortices and adjacent temporal regions are sufficient to generate early syntactic negativities in the auditory event-related potential (ERP). We tested ten clinically non-aphasic patients with left inferior frontal lesions, but intact temporal cortices in a passive auditory ERP paradigm that had reliably elicited early negativities in response to violations of subject-verb agreement and word category in the past. Subject-verb agreement violations failed to elicit early grammaticality effects in these patients, whereas a group of ten age-matched controls showed a reliable early negativity. This finding supports the idea that sensory aspects of syntactic analysis as reflected in early syntactic negativities critically depend on top-down predictions generated by the left inferior frontal cortex. In contrast, word category violations elicited a small, marginally significant early negativity both in controls and patients, suggesting an additional involvement of temporal regions in early phrase structure processing. In an additional auditory oddball experiment patients showed a regular P300, but no N2b component in response to deviant tones, indicating that their deficit in generating sensory predictions extends beyond the language domain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Medial frontal cortex and response conflict: Evidence from human intracranial EEG and medial frontal cortex lesion

    NARCIS (Netherlands)

    Cohen, M.X.; Ridderinkhof, K.R.; Haupt, S.; Elger, C.E.; Fell, J.

    2008-01-01

    The medial frontal cortex (MFC) has been implicated in the monitoring and selection of actions in the face of competing alternatives, but much remains unknown about its functional properties, including electrophysiological oscillations, during response conflict tasks. Here, we recorded intracranial

  7. Responses of primate frontal cortex neurons during natural vocal communication

    OpenAIRE

    Miller, Cory T.; Thomas, A. Wren; Nummela, Samuel U.; de la Mothe, Lisa A.

    2015-01-01

    The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed ...

  8. Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity

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    Hiroyuki Fujita

    2016-01-01

    Full Text Available Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM. The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb levels during standing during single (S-S, standing during dual (S-D, one leg standing during single (O-S, and one leg standing during dual (O-D tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance.

  9. The relative contributions of frontal and parietal cortex for generalized quantifier comprehension

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    Christopher A Olm

    2014-08-01

    Full Text Available Quantifiers, like some or few, are frequent in daily language. Linguists posit at least three distinct classes of quantifiers: cardinal quantifiers that rely on numerosity, majority quantifiers that additionally depend on executive resources, and logical quantifiers that rely on perceptual attention. We used BOLD fMRI to investigate the roles of frontal and parietal regions in quantifier comprehension. Participants performed a sentence-picture verification task to determine whether a sentence containing a quantifier accurately describes a picture. A whole-brain analysis identified a network involved in quantifier comprehension: This implicated bilateral inferior parietal, superior parietal and dorsolateral prefrontal cortices, and right inferior frontal cortex. We then performed region-of-interest analyses to assess the relative contribution of each region for each quantifier class. Inferior parietal cortex was equally activated across all quantifier classes, consistent with prior studies implicating the region for quantifier comprehension due in part to its role in the representation of number knowledge. Right superior parietal cortex was up-regulated in comparison to frontal regions for cardinal and logical quantifiers, but parietal and frontal regions were equally activated for majority quantifiers and each frontal region is most highly activated for majority quantifiers. This finding is consistent with the hypothesis that majority quantifiers rely on numerosity mechanisms in parietal cortex and executive mechanisms in frontal cortex. Also, right inferior frontal cortex was up-regulated for logical compared to cardinal quantifiers, which may be related to selection demands associated with logical quantifier comprehension. We conclude that distinct components of a large-scale fronto-parietal network contribute to specific aspects of quantifier comprehension, and that this biologically-defined network is consistent with cognitive theories of

  10. On the functional relevance of frontal cortex for passive and voluntarily controlled bistable vision.

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    de Graaf, Tom A; de Jong, Maartje C; Goebel, Rainer; van Ee, Raymond; Sack, Alexander T

    2011-10-01

    In bistable vision, one constant ambiguous stimulus leads to 2 alternating conscious percepts. This perceptual switching occurs spontaneously but can also be influenced through voluntary control. Neuroimaging studies have reported that frontal regions are activated during spontaneous perceptual switches, leading some researchers to suggest that frontal regions causally induce perceptual switches. But the opposite also seems possible: frontal activations may themselves be caused by spontaneous switches. Classically implicated in attentional processes, these same regions are also candidates for the origins of voluntary control over bistable vision. Here too, it remains unknown whether frontal cortex is actually functionally relevant. It is even possible that spontaneous perceptual switches and voluntarily induced switches are mediated by the same top-down mechanisms. To directly address these issues, we here induced "virtual lesions," with transcranial magnetic stimulation, in frontal, parietal, and 2 lower level visual cortices using an established ambiguous structure-from-motion stimulus. We found that dorsolateral prefrontal cortex was causally relevant for voluntary control over perceptual switches. In contrast, we failed to find any evidence for an active role of frontal cortex in passive bistable vision. Thus, it seems the same pathway used for willed top-down modulation of bistable vision is not used during passive bistable viewing.

  11. Role of Frontal Alpha Oscillations in Creativity

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    Lustenberger, Caroline; Boyle, Michael R.; Foulser, A. Alban; Mellin, Juliann M.; Fröhlich, Flavio

    2015-01-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent EEG data suggests that cortical oscillations in the alpha frequency band (8 – 12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a fundamental role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking, a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40Hz-tACS was used in instead of 10Hz-tACS to rule out a general “electrical stimulation” effect. No significant change in the Creativity Index was found for such frontal gamma stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

  12. Ventrolateral and dorsomedial frontal cortex lesions impair mnemonic context retrieval.

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    Chapados, Catherine; Petrides, Michael

    2015-02-22

    The prefrontal cortex appears to contribute to the mnemonic retrieval of the context within which stimuli are experienced, but only under certain conditions that remain to be clarified. Patients with lesions to the frontal cortex, the temporal lobe and neurologically intact individuals were tested for context memory retrieval when verbal stimuli (words) had been experienced across multiple (unstable context condition) or unique (stable context condition) contexts; basic recognition memory of these words-in-contexts was also tested. Patients with lesions to the right ventrolateral prefrontal cortex (VLPFC) were impaired on context retrieval only when the words had been seen in multiple contexts, demonstrating that this prefrontal region is critical for active retrieval processing necessary to disambiguate memory items embedded across multiple contexts. Patients with lesions to the left dorsomedial prefrontal region were impaired on both context retrieval conditions, regardless of the stability of the stimulus-to-context associations. Conversely, prefrontal lesions sparing the ventrolateral and dorsomedial regions did not impair context retrieval. Only patients with temporal lobe excisions were impaired on basic recognition memory. The results demonstrate a basic contribution of the left dorsomedial frontal region to mnemonic context retrieval, with the VLPFC engaged, selectively, when contextual relations are unstable and require disambiguation. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  13. Occipital cortex of blind individuals is functionally coupled with executive control areas of frontal cortex.

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    Deen, Ben; Saxe, Rebecca; Bedny, Marina

    2015-08-01

    In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity.

  14. Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal cortex under the pathological conditions of Alzheimer's disease.

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    Jiang, Qiong; Chen, Shuangxi; Hu, Chengliang; Huang, Peizhi; Shen, Huifan; Zhao, Weijiang

    2016-09-01

    Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop in the elderly, is characterized by the deposition of β‑amyloid protein (Aβ) and extensive neuronal cell death in the brain. Neuregulin‑1 (Nrg1)‑mediated intercellular and intracellular communication via binding to ErbB receptors regulates a diverse set of biological processes involved in the development of the nervous system. In the present study, a linear correlation was identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a human cortical tissue microarray. In addition, increased expression levels of Nrg1, but reduced pErbB receptor levels, were detected in the frontal lobe of a patient with AD. Western blotting and immunofluorescence staining were subsequently performed to uncover the potential preventive role of Nrg1 in cortical neurons affected by the neurodegenerative processes of AD. It was observed that the expression of Nrg1 increased as the culture time of the cortical neurons progressed. In addition, H2O2 and Aβ1‑42, two inducers of oxidative stress and neuronal damage, led to a dose‑dependent decrease in Nrg1 expression. Recombinant Nrg1β, however, was revealed to exert a pivotal role in preventing oxidative stress and neuronal damage from occurring in the mouse cortical neurons. Taken together, these results suggest that changes in Nrg1 signaling may influence the pathological development of AD, and exogenous Nrg1 may serve as a potential candidate for the prevention and treatment of AD.

  15. Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex

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    O.A. Olulade

    2015-01-01

    Full Text Available fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called “visual word form area”, VWFA, is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009. Similarly, the left inferior frontal cortex (IFC has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007. Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009. Building on these studies, we here (1 investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2 compare typically reading with dyslexic children, and (3 examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We

  16. Cholinergic receptor binding in the frontal cortex of suicide victims

    International Nuclear Information System (INIS)

    Stanley, M.

    1986-01-01

    Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

  17. Oxidative and glicolytic metabolism of the frontal cortex (latero-frontal) and of the posterior cortex (latero-occipital) in relation with the sexual activity of the rat.

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    Menéndez-Patterson, A; Florez-Lozano, J A; Marin, B

    1976-01-01

    The authors of this paper have ascertained the glycolytic metabolism and the oxidative metabolism (intake of QO2), of the frontal and posterior cortex in female rats at different stages of the sexual cycle, as also in ovariectomized animals, by the intake of glucose and the production of lactates. The results indicate a statistically significant increase of the oxidative metabolism of the posterior cortex (latero-occipital) in the estrual and proestrual phases, in comparisons with the diestral phase. The frontal cortex (latero-frontal) did not show any significant difference; moreover, the glycolitic metabolism did not alter in any of the tissues under observation. These findings, seem to suggest possible participation of the posterior cortex (latero-occipital) on the regulation of sexual cycle of the rat. The activation of this cortex occurs through the preponderant imbricantion of the tri-carboxylic acid cycle.

  18. Cognitive priming in sung and instrumental music: activation of inferior frontal cortex.

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    Tillmann, B; Koelsch, S; Escoffier, N; Bigand, E; Lalitte, P; Friederici, A D; von Cramon, D Y

    2006-07-15

    Neural correlates of the processing of musical syntax-like structures have been investigated via expectancy violation due to musically unrelated (i.e., unexpected) events in musical contexts. Previous studies reported the implication of inferior frontal cortex in musical structure processing. However - due to the strong musical manipulations - activations might be explained by sensory deviance detection or repetition priming. Our present study investigated neural correlates of musical structure processing with subtle musical violations in a musical priming paradigm. Instrumental and sung sequences ended on related and less-related musical targets. The material controlled sensory priming components, and differences in target processing required listeners' knowledge on musical structures. Participants were scanned with functional Magnetic Resonance Imaging (fMRI) while performing speeded phoneme and timbre identification judgments on the targets. Behavioral results acquired in the scanner replicated the facilitation effect of related over less-related targets. The blood oxygen level-dependent (BOLD) signal linked to target processing revealed activation of right inferior frontal areas (i.e., inferior frontal gyrus, frontal operculum, anterior insula) that was stronger for less-related than for related targets, and this was independent of the material carrying the musical structures. This outcome points to the implication of inferior frontal cortex in the processing of syntactic relations also for musical material and to its role in the processing and integration of sequential information over time. In addition to inferior frontal activation, increased activation was observed in orbital gyrus, temporal areas (anterior superior temporal gyrus, posterior superior temporal gyrus and sulcus, posterior middle temporal gyrus) and supramarginal gyrus.

  19. The role of medial frontal gyrus in action anticipation in professional badminton players

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    Huan Xu

    2016-11-01

    Full Text Available Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent (BOLD activation was assessed by means of functional magnetic resonance imaging (fMRI. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex. Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate

  20. Reversed Procrastination by Focal Disruption of Medial Frontal Cortex.

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    Jha, Ashwani; Diehl, Beate; Scott, Catherine; McEvoy, Andrew W; Nachev, Parashkev

    2016-11-07

    An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Human medial frontal cortex activity predicts learning from errors.

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    Hester, Robert; Barre, Natalie; Murphy, Kevin; Silk, Tim J; Mattingley, Jason B

    2008-08-01

    Learning from errors is a critical feature of human cognition. It underlies our ability to adapt to changing environmental demands and to tune behavior for optimal performance. The posterior medial frontal cortex (pMFC) has been implicated in the evaluation of errors to control behavior, although it has not previously been shown that activity in this region predicts learning from errors. Using functional magnetic resonance imaging, we examined activity in the pMFC during an associative learning task in which participants had to recall the spatial locations of 2-digit targets and were provided with immediate feedback regarding accuracy. Activity within the pMFC was significantly greater for errors that were subsequently corrected than for errors that were repeated. Moreover, pMFC activity during recall errors predicted future responses (correct vs. incorrect), despite a sizeable interval (on average 70 s) between an error and the next presentation of the same recall probe. Activity within the hippocampus also predicted future performance and correlated with error-feedback-related pMFC activity. A relationship between performance expectations and pMFC activity, in the absence of differing reinforcement value for errors, is consistent with the idea that error-related pMFC activity reflects the extent to which an outcome is "worse than expected."

  2. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey

    International Nuclear Information System (INIS)

    Petrides, M.; Pandya, D.N.

    1988-01-01

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus

  3. Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress

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    Laura eMusazzi

    2015-04-01

    Full Text Available Increasing evidence has shown that the pathophysiology of neuropsychiatric disorders, including mood disorders, is associated with abnormal function and regulation of the glutamatergic system. Consistently, preclinical studies on stress-based animal models of pathology showed that glucocorticoids and stress exert crucial effects on neuronal excitability and function, especially in cortical and limbic areas. In prefrontal and frontal cortex, acute stress was shown to induce enhancement of glutamate release/transmission dependent on activation of corticosterone receptors. Although the mechanisms whereby stress affects glutamate transmission have not yet been fully understood, it was shown that synaptic, non-genomic action of corticosterone is required to increase the readily releasable pool of glutamate vesicles but is not sufficient to enhance transmission in prefrontal and frontal cortex. Slower, partly genomic mechanisms are probably necessary for the enhancement of glutamate transmission induced by stress.Combined evidence has suggested that the changes in glutamate release and transmission are responsible for the dendritic remodeling and morphological changes induced by stress and it has been argued that sustained alterations of glutamate transmission may play a key role in the long-term structural/functional changes associated with mood disorders in patients. Intriguingly, modifications of the glutamatergic system induced by stress in the prefrontal cortex seem to be biphasic. Indeed, while the fast response to stress suggests an enhancement in the number of excitatory synapses, synaptic transmission and working memory, long-term adaptive changes -including those consequent to chronic stress- induce opposite effects. Better knowledge of the cellular effectors involved in this biphasic effect of stress may be useful to understand the pathophysiology of stress-related disorders, and open new paths for the development of therapeutic approaches.

  4. Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein.

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    Anderson, B; Harvey, T

    1996-06-07

    Neuronal density, neuron size, and the number of neurons under 1 mm2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

  5. Chronometric electrical stimulation of right inferior frontal cortex increases motor braking.

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    Wessel, Jan R; Conner, Christopher R; Aron, Adam R; Tandon, Nitin

    2013-12-11

    The right inferior frontal cortex (rIFC) is important for stopping responses. Recent research shows that it is also activated when response emission is slowed down when stopping is anticipated. This suggests that rIFC also functions as a goal-driven brake. Here, we investigated the causal role of rIFC in goal-driven braking by using computer-controlled, event-related (chronometric), direct electrical stimulation (DES). We compared the effects of rIFC stimulation on trials in which responses were made in the presence versus absence of a stopping-goal ("Maybe Stop" [MS] vs "No Stop" [NS]). We show that DES of rIFC slowed down responses (compared with control-site stimulation) and that rIFC stimulation induced more slowing when motor braking was required (MS) compared with when it was not (NS). Our results strongly support a causal role of a rIFC-based network in inhibitory motor control. Importantly, the results extend this causal role beyond externally driven stopping to goal-driven inhibitory control, which is a richer model of human self-control. These results also provide the first demonstration of double-blind chronometric DES of human prefrontal cortex, and suggest that--in the case of rIFC--this could lead to augmentation of motor braking.

  6. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

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    Lieblein-Boff, Jacqueline C; Johnson, Elizabeth J; Kennedy, Adam D; Lai, Chron-Si; Kuchan, Matthew J

    2015-01-01

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  7. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  8. Trait aggression and trait impulsivity are not related to frontal cortex 5-HT2A receptor binding in healthy individuals

    DEFF Research Database (Denmark)

    da Cunha-Bang, Sophie; Stenbæk, Dea Siggaard; Holst, Klaus

    2013-01-01

    age 47.0±18.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [(18)F]-altanserin PET imaging. Trait aggression and trait impulsivity were assessed with the Buss-Perry Aggression Questionnaire (AQ...... and the AQ or BIS-11 total scores. Also, there was no significant interaction between gender and frontal cortex 5-HT2AR in predicting trait aggression and trait impulsivity. This is the first study to examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large sample of healthy...... individuals. Our findings are not supportive of a selective role for 5-HT2AR in mediating the 5-HT related effects on aggression and impulsivity in psychiatrically healthy individuals....

  9. Differential responses to ω-agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks.

    Science.gov (United States)

    Knaack, Gretchen L; Charkhkar, Hamid; Hamilton, Franz W; Peixoto, Nathalia; O'Shaughnessy, Thomas J; Pancrazio, Joseph J

    2013-07-01

    ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50 nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects

    Directory of Open Access Journals (Sweden)

    Cao Fujiang

    2012-09-01

    Full Text Available Abstract Background Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. To date the etiology of this disorder is poorly understood. Studies suggest that astrocytes play critical roles in neural plasticity by detecting neuronal activity and modulating neuronal networks. Recently, a number of studies suggested that an abnormal function of glia/astrocytes may be involved in the development of autism. However, there is yet no direct evidence showing how astrocytes develop in the brain of autistic individuals. Methods Study subjects include brain tissue from autistic subjects, BTBR T + tfJ (BTBR and Neuroligin (NL-3 knock-down mice. Western blot analysis, Immunohistochemistry and confocal microscopy studies have be used to examine the density and morphology of astrocytes, as well as Wnt and β-catenin protein expression. Results In this study, we demonstrate that the astrocytes in autisitcsubjects exhibit significantly reduced branching processes, total branching length and cell body sizes. We also detected an astrocytosis in the frontal cortex of autistic subjects. In addition, we found that the astrocytes in the brain of an NL3 knockdown mouse exhibited similar alterations to what we found in the autistic brain. Furthermore, we detected that both Wnt and β-catenin proteins are decreased in the frontal cortex of autistic subjects. Wnt/β-catenin pathway has been suggested to be involved in the regulation of astrocyte development. Conclusions Our findings imply that defects in astrocytes could impair neuronal plasticity and partially contribute to the development of autistic-like behaviors in both humans and mice. The alteration of Wnt/β-catenin pathway in the brain of autistic subjects may contribute to the changes of astrocytes.

  11. Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment.

    Science.gov (United States)

    Sanguedo, Frederico Velasco; Dias, Caio Vitor Bueno; Dias, Flavia Regina Cruz; Samuels, Richard Ian; Carey, Robert J; Carrera, Marinete Pinheiro

    2016-03-01

    Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. Assess the role of the amygdala in emotional responses. Experimental manipulations were performed in which environmental familiarity was the variable. To provide the maximal degree of familiarity, ERK was measured after removal from the home cage and re-placement back into the same cage. To maximize exposure to an unfamiliar environment, ERK was measured following placement into a novel open field. To assess whether familiarity was the critical variable in the ERK response to the novel open field, ERK was also measured after either four or eight placements into the same environment. ERK quantification was carried out in the amygdala, frontal cortex, and the nucleus accumbens. After home cage re-placement, ERK activation was found in the frontal cortex and nucleus accumbens but was absent in the amygdala. Following placement in a novel environment, ERK activation was more prominent in the amygdala than the frontal cortex or nucleus accumbens. In contrast, with habituation to the novel environment, ERK phosphors declined markedly in the amygdala but increased in the frontal cortex and nucleus accumbens to the level observed following home cage re-placement. The differential responsiveness of the amygdala versus the frontal cortex and the nucleus accumbens to a novel versus a habituated environment is consistent with a reciprocal interaction between these neural systems and points to their important role in the mediation of behavioral activation to novelty and behavioral inactivation with habituation.

  12. Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex

    DEFF Research Database (Denmark)

    Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z

    2017-01-01

    degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during...

  13. Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

    Science.gov (United States)

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

    2006-01-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

  14. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides

    International Nuclear Information System (INIS)

    Stanley, M.; Virgilio, J.; Gershon, S.

    1982-01-01

    Binding characteristics of tritiated imipramine were determined in the frontal cortex of suicides and well-matched controls. Maximal binding was significantly lower in brains from the suicides. This finding is consistent with reports of decreased tritiated imipramine binding in the platelets of patients diagnosed as having a major affective disorder

  15. Selective involvement of superior frontal cortex during working memory for shapes.

    Science.gov (United States)

    Yee, Lydia T S; Roe, Katherine; Courtney, Susan M

    2010-01-01

    A spatial/nonspatial functional dissociation between the dorsal and ventral visual pathways is well established and has formed the basis of domain-specific theories of prefrontal cortex (PFC). Inconsistencies in the literature regarding prefrontal organization, however, have led to questions regarding whether the nature of the dissociations observed in PFC during working memory are equivalent to those observed in the visual pathways for perception. In particular, the dissociation between dorsal and ventral PFC during working memory for locations versus object identities has been clearly present in some studies but not in others, seemingly in part due to the type of objects used. The current study compared functional MRI activation during delayed-recognition tasks for shape or color, two object features considered to be processed by the ventral pathway for perceptual recognition. Activation for the shape-delayed recognition task was greater than that for the color task in the lateral occipital cortex, in agreement with studies of visual perception. Greater memory-delay activity was also observed, however, in the parietal and superior frontal cortices for the shape than for the color task. Activity in superior frontal cortex was associated with better performance on the shape task. Conversely, greater delay activity for color than for shape was observed in the left anterior insula and this activity was associated with better performance on the color task. These results suggest that superior frontal cortex contributes to performance on tasks requiring working memory for object identities, but it represents different information about those objects than does the ventral frontal cortex.

  16. Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex.

    Science.gov (United States)

    Dvorkin, Anna; Silva, Charmaine; McMurran, Thomas; Bisnaire, Liane; Foster, Jane; Szechtman, Henry

    2010-11-01

    The quinpirole sensitization model of obsessive-compulsive disorder was used to investigate the functional role that brain regions implicated in a neuroanatomical circuit of obsessive-compulsive disorder may play in compulsive checking behavior. Following repeated injections of saline or quinpirole (0.5mg/kg, twice per week, ×8 injections) to induce compulsive checking, rats received N-methyl-d-aspartate lesions of the nucleus accumbens core (NAc), orbital frontal cortex (OFC) and basolateral amygdala, or sham lesions. When retested at 17days post-surgery, the results showed effects of NAc and OFC but not basolateral amygdala lesion. NAc lesions affected measures indicative of the amount of checking behavior, whereas OFC lesions affected indices of staying away from checking. The pattern of results suggested that the functional roles of the NAc and OFC in checking behavior are to control the vigor of motor performance and focus on goal-directed activity, respectively. Furthermore, similarities in behavior between quinpirole sham rats and saline NAc lesion rats suggested that quinpirole may drive the vigor of checking by inhibition of NAc neurons, and that the NAc may be a site for the negative feedback control of checking. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  17. Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

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    Bjorvatn, B; Grønli, J; Hamre, F; Sørensen, E; Fiske, E; Bjorkum, Alvhild Alette; Portas, CM; Ursin, R

    2002-01-01

    Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored b...

  18. Functional role of frontal alpha oscillations in creativity.

    Science.gov (United States)

    Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

    2015-06-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Reward expectation and prediction error in human medial frontal cortex: an EEG study.

    Science.gov (United States)

    Silvetti, Massimo; Nuñez Castellar, Elena; Roger, Clémence; Verguts, Tom

    2014-01-01

    The mammalian medial frontal cortex (MFC) is involved in reward-based decision making. In particular, in nonhuman primates this area constructs expectations about upcoming rewards, given an environmental state or a choice planned by the animal. At the same time, in both humans and nonhuman primates, the MFC computes the difference between such predictions and actual environmental outcomes (reward prediction errors). However, there is a paucity of evidence about the time course of MFC-related activity during reward prediction and prediction error in humans. Here we experimentally investigated this by recording the EEG during a reinforcement learning task. Our results support the hypothesis that human MFC codes for reward prediction during the cue period and for prediction error during the outcome period. Further, reward expectation (cue period) was positively correlated with prediction error (outcome period) in error trials but negatively in correct trials, consistent with updating of reward expectation by prediction error. This demonstrates in humans, like in nonhuman primates, a role of the MFC in the rapid updating of reward expectations through prediction errors. © 2013.

  20. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

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    Yang, C.; Guo, X. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wang, G.H. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wuhan University, Institute of Neuropsychiatry, Wuhan, China, Institute of Neuropsychiatry, Wuhan University, Wuhan (China); Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China)

    2014-03-03

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  1. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    International Nuclear Information System (INIS)

    Yang, C.; Guo, X.; Wang, G.H.; Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y.

    2014-01-01

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD

  2. Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex

    Science.gov (United States)

    Pinto, Joshua G. A.; Jones, David G.; Murphy, Kathryn M.

    2013-01-01

    Two theories have influenced our understanding of cortical development: the integrated network theory, where synaptic development is coordinated across areas; and the cascade theory, where the cortex develops in a wave-like manner from sensory to non-sensory areas. These different views on cortical development raise challenges for current studies aimed at comparing detailed maturation of the connectome among cortical areas. We have taken a different approach to compare synaptic development in rat visual, somatosensory, and frontal cortex by measuring expression of pre-synaptic (synapsin and synaptophysin) proteins that regulate vesicle cycling, and post-synaptic density (PSD-95 and Gephyrin) proteins that anchor excitatory or inhibitory (E-I) receptors. We also compared development of the balances between the pairs of pre- or post-synaptic proteins, and the overall pre- to post-synaptic balance, to address functional maturation and emergence of the E-I balance. We found that development of the individual proteins and the post-synaptic index overlapped among the three cortical areas, but the pre-synaptic index matured later in frontal cortex. Finally, we applied a neuroinformatics approach using principal component analysis and found that three components captured development of the synaptic proteins. The first component accounted for 64% of the variance in protein expression and reflected total protein expression, which overlapped among the three cortical areas. The second component was gephyrin and the E-I balance, it emerged as sequential waves starting in somatosensory, then frontal, and finally visual cortex. The third component was the balance between pre- and post-synaptic proteins, and this followed a different developmental trajectory in somatosensory cortex. Together, these results give the most support to an integrated network of synaptic development, but also highlight more complex patterns of development that vary in timing and end point among the

  3. Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex.

    Science.gov (United States)

    Pinto, Joshua G A; Jones, David G; Murphy, Kathryn M

    2013-01-01

    Two theories have influenced our understanding of cortical development: the integrated network theory, where synaptic development is coordinated across areas; and the cascade theory, where the cortex develops in a wave-like manner from sensory to non-sensory areas. These different views on cortical development raise challenges for current studies aimed at comparing detailed maturation of the connectome among cortical areas. We have taken a different approach to compare synaptic development in rat visual, somatosensory, and frontal cortex by measuring expression of pre-synaptic (synapsin and synaptophysin) proteins that regulate vesicle cycling, and post-synaptic density (PSD-95 and Gephyrin) proteins that anchor excitatory or inhibitory (E-I) receptors. We also compared development of the balances between the pairs of pre- or post-synaptic proteins, and the overall pre- to post-synaptic balance, to address functional maturation and emergence of the E-I balance. We found that development of the individual proteins and the post-synaptic index overlapped among the three cortical areas, but the pre-synaptic index matured later in frontal cortex. Finally, we applied a neuroinformatics approach using principal component analysis and found that three components captured development of the synaptic proteins. The first component accounted for 64% of the variance in protein expression and reflected total protein expression, which overlapped among the three cortical areas. The second component was gephyrin and the E-I balance, it emerged as sequential waves starting in somatosensory, then frontal, and finally visual cortex. The third component was the balance between pre- and post-synaptic proteins, and this followed a different developmental trajectory in somatosensory cortex. Together, these results give the most support to an integrated network of synaptic development, but also highlight more complex patterns of development that vary in timing and end point among the

  4. Indolic substances in plasma, cerebrospinal fluid, and frontal cortex of human subjects infused with saline or tryptophan.

    Science.gov (United States)

    Gillman, P K; Bartlett, J R; Bridges, P K; Hunt, A; Patel, A J; Kantamaneni, B D; Curzon, G

    1981-08-01

    Psychiatric patients undergoing the psychosurgical operation of stereotactic subcaudate tractotomy were infused intravenously with either saline or L-tryptophan (15 mg/kg/h). Plasma, lumbar cerebrospinal fluid (CSF), ventricular CSF and a specimen of frontal cortex were collected. The relationships of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentration of tryptophan in the cortex and CSF were investigated. Tryptophan infusion resulted in plasma tryptophan values comparable to those found after oral doses used in treating depression or insomnia, and about sixfold increases of tryptophan in the cerebral cortex. Increased brain 5-hydroxytryptamine synthesis was indicated by significant rises of CSF 5-hydroxyindoleacetic acid. The concentration of plasma free tryptophan was a better predictor than plasma total tryptophan of cortex tryptophan concentration. As all correlation coefficients of plasma versus brain or plasma versus ventricular CSF tryptophan concentrations were decreased when allowance was made for differences of concentration of large neutral amino acids, the results suggest that the role of these substances within their physiological range as inhibitors of tryptophan transport to the brain may previously have been overemphasised.

  5. Genes encoding heterotrimeric G-proteins are associated with gray matter volume variations in the medial frontal cortex.

    Science.gov (United States)

    Chavarría-Siles, Iván; Rijpkema, Mark; Lips, Esther; Arias-Vasquez, Alejandro; Verhage, Matthijs; Franke, Barbara; Fernández, Guillén; Posthuma, Danielle

    2013-05-01

    G-protein-coupled signal transduction mediates most cellular responses to hormones and neurotransmitters; this signaling system transduces a large variety of extracellular stimuli into neurons and is the most widely used mechanism for cell communication at the synaptic level. The heterotrimeric G-proteins have been well established as key regulators of neuronal growth, differentiation, and function. More recently, the heterotrimeric G-protein genes group was associated with general cognitive ability. Although heterotrimeric G-proteins are linked to both cognitive ability and neuron signaling, it is unknown whether heterotrimeric G-proteins are also important for brain structure. We tested for association between local cerebral gray matter volume and the heterotrimeric G-protein genes group in 294 subjects; a replication analysis was performed in an independent sample of 238 subjects. Voxel-based morphometry revealed a strong replicated association between 2 genes encoding heterotrimeric G-proteins with specific local increase in medial frontal cortex volume, an area known to be involved in cognitive control and negative affect. This finding suggests that heterotrimeric G-proteins might modulate medial frontal cortex gray matter volume. The differences in gray matter volume due to variations in genes encoding G-proteins may be explained by the role of G-proteins in prenatal and postnatal neocortex development.

  6. α₂-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims.

    Science.gov (United States)

    Valdizán, Elsa M; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A; Meana, J Javier; Pazos, Angel

    2010-11-01

    Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α₂(A)-adrenoceptors in postmortem frontal cortex of depressed subjects. G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α₂-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Basal [³⁵S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [³⁵S] GTPγS binding potency (EC₅₀ = .58 μmol/L vs. EC₅₀ = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (I(max) = 27 ± 4% vs. I(max) = 47 ± 5%; p < .01) were observed after incubation with the α(2)-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC₅₀ values for [³⁵S] GTPγS and I(max) values for AC assay was found (n = 30; r = -.43; p < .05). The dual regulation of α(2A)-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gα(i/o)-protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α₂(A)-adrenoceptors in the pathogenesis of depression. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. α2-Adrenoceptor Functionality in Postmortem Frontal Cortex of Depressed Suicide Victims

    Science.gov (United States)

    Valdizán, Elsa M.; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A.; Meana, J. Javier; Pazos, Angel

    2013-01-01

    Background Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α2A-adrenoceptors in postmortem frontal cortex of depressed subjects. Methods G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α2-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Results Basal [35S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [35S] GTPγS binding potency (EC50 = .58 μmol/L vs. EC50 = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (Imax = 27 ± 4% vs. Imax = 47 ± 5%; p < .01) were observed after incubation with the α2-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC50 values for [35S] GTPγS and Imax values for AC assay was found (n = 30; r = −.43; p < .05). Conclusions The dual regulation of α2A-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gαi/o–protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α2A-adrenoceptors in the pathogenesis of depression. PMID:20864091

  8. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

    Directory of Open Access Journals (Sweden)

    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  9. STRUCTURAL CONNECTIVITY OF BROCA’S AREA AND MEDIAL FRONTAL CORTEX

    Science.gov (United States)

    Ford, Anastasia; McGregor, Keith M.; Case, Kimberly; Crosson, Bruce; White, Keith D.

    2010-01-01

    Despite over 140 years of research on Broca’s area, the connections of this region to medial frontal cortex remain unclear. The current study investigates this structural connectivity using diffusion weighted MRI tractography in living humans. Our results show connections between Broca’s area and Brodmann’s areas (BA) 9, 8, and 6 (both supplementary motor area (SMA) in caudal BA 6, and Pre-SMA in rostral BA 6). Trajectories follow an anterior-to-posterior gradient, wherein the most anterior portions of Broca’s area connect to BA 9 and 8 while posterior Broca’s area connects to Pre-SMA and SMA. This anterior-posterior connectivity gradient is also present when connectivity-based parcellation of Broca’s area is performed. Previous studies of language organization suggest involvement of anterior Broca’s area in semantics and posterior Broca’s area in syntax/phonology. Given corresponding patterns of functional and structural organization of Broca’s area, it seems well warranted to investigate carefully how anterior vs. posterior medial frontal cortex differentially affect semantics, syntax and phonology. PMID:20488246

  10. The scarcity heuristic impacts reward processing within the medial-frontal cortex.

    Science.gov (United States)

    Williams, Chad C; Saffer, Boaz Y; McCulloch, Robert B; Krigolson, Olave E

    2016-05-04

    Objects that are rare are often perceived to be inherently more valuable than objects that are abundant - a bias brought about in part by the scarcity heuristic. In the present study, we sought to test whether perception of rarity impacted reward evaluation within the human medial-frontal cortex. Here, participants played a gambling game in which they flipped rare and abundant 'cards' on a computer screen to win financial rewards while electroencephalographic data were recorded. Unbeknownst to participants, reward outcome and frequency was random and equivalent for both rare and abundant cards; thus, only a perception of scarcity was true. Analysis of the electroencephalographic data indicated that the P300 component of the event-related brain potential differed in amplitude for wins and losses following the selection of rare cards, but not following the selection of abundant cards. Importantly, then, we found that the perception of card rarity impacted reward processing even though reward feedback was independent of and subsequent to card selection. Our data indicate a top-down influence of the scarcity heuristic on reward evaluation, and specifically the processing of reward magnitude, within the human medial-frontal cortex.

  11. Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

    Science.gov (United States)

    Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

    2016-01-01

    Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

  12. What makes the dorsomedial frontal cortex active during reading the mental states of others?

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    Masaki eIsoda

    2013-12-01

    Full Text Available The dorsomedial frontal part of the cerebral cortex is consistently activated when people read the mental states of others, such as their beliefs, desires, and intentions, the ability known as having a theory of mind (ToM or mentalizing. This ubiquitous finding has led many researchers to conclude that the dorsomedial frontal cortex (DMFC constitutes a core component in mentalizing networks. Despite this, it remains unclear why the DMFC becomes active during ToM tasks. We argue that key psychological and behavioral aspects in mentalizing are closely associated with DMFC functions. These include executive inhibition, distinction between self and others, prediction under uncertainty, and perception of intentions, all of which are important for predicting others’ intention and behavior. We review the literature supporting this claim, ranging in fields from developmental psychology to human neuroimaging and macaque electrophysiology. Because perceiving intentions in others’ actions initiates mentalizing and forms the basis of virtually all types of social interaction, the fundamental issue in social neuroscience is to determine the aspects of physical entities that make an observer perceive that they are intentional beings and to clarify the neurobiological underpinnings of the perception of intentionality in others’ actions.

  13. [Interaction between neurons of the frontal cortex and hippocampus during the realization of choice of food reinforcement quality in cats].

    Science.gov (United States)

    Merzhanova, G Kh; Dolbakian, E E; Khokhlova, V N

    2003-01-01

    Six cats were subjected to the procedure of appetitive instrumental conditioning (with light as a conditioned stimuls) by the method of the "active choice" of reinforcement quality. Short-delay conditioned bar-press responses were rewarded with bread-meat mixture, and the delayed responses were reinforced by meat. The animals differed in behavior strategy: four animals preferred the bar-pressing with a long delay (the so-called "self-control" group), and two cats preferred the bar-pressing with a short delay (the so-called "impulsive" group). Multiunit activity in the frontal cortex and hippocampus (CA3) was recorded via chronically implanted nichrome wire semimicroelectrodes. An interaction between the neighboring neurons in the frontal cortex and hippocampus (within local neural networks) and between the neurons of the frontal cortex and hippocampus (distributed neural networks in frontal-hippocampal and hippocampal-frontal directions) was evaluated by means of statistical crosscorrelation analysis of spike trains. Crosscorrelations between neuronal spike trains in the delay range of 0-100 ms were explored. It was shown that the number of crosscorrelations between the neuronal discharges both in the local and distributed networks was significantly higher in the "self-control" cats. It was suggested that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures which determine the behavioral strategy of animals in the "self-control" group.

  14. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation.

    Science.gov (United States)

    Nagarajan, Raman P; Hogart, Amber R; Gwye, Ynnez; Martin, Michelle R; LaSalle, Janine M

    2006-01-01

    Mutations in MECP2, encoding methyl CpG binding protein 2 (MeCP2), cause most cases of Rett syndrome (RTT), an X-linked neurodevelopmental disorder. Both RTT and autism are "pervasive developmental disorders" and share a loss of social, cognitive and language skills and a gain in repetitive stereotyped behavior, following apparently normal perinatal development. Although MECP2 coding mutations are a rare cause of autism, MeCP2 expression defects were previously found in autism brain. To further study the role of MeCP2 in autism spectrum disorders (ASDs), we determined the frequency of MeCP2 expression defects in brain samples from autism and other ASDs. We also tested the hypotheses that MECP2 promoter mutations or aberrant promoter methylation correlate with reduced expression in cases of idiopathic autism. MeCP2 immunofluorescence in autism and other neurodevelopmental disorders was quantified by laser scanning cytometry and compared with control postmortem cerebral cortex samples on a large tissue microarray. A significant reduction in MeCP2 expression compared to age-matched controls was found in 11/14 autism (79%), 9/9 RTT (100%), 4/4 Angelman syndrome (100%), 3/4 Prader-Willi syndrome (75%), 3/5 Down syndrome (60%), and 2/2 attention deficit hyperactivity disorder (100%) frontal cortex samples. One autism female was heterozygous for a rare MECP2 promoter variant that correlated with reduced MeCP2 expression. A more frequent occurrence was significantly increased MECP2 promoter methylation in autism male frontal cortex compared to controls. Furthermore, percent promoter methylation of MECP2 significantly correlated with reduced MeCP2 protein expression. These results suggest that both genetic and epigenetic defects lead to reduced MeCP2 expression and may be important in the complex etiology of autism.

  15. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

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    Kei Mizuno

    2015-01-01

    Full Text Available The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS. We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG, which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

  16. Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers

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    Andrew S. Kayser

    2017-01-01

    Full Text Available Failures of self-regulation in problem and pathological gambling (PPG are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patients with addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT, reduced delay discounting, a measure of impulsivity, in healthy subjects. To evaluate this potentially translational approach to augmenting prefrontal inhibitory control, here we hypothesized that increasing cortical dopamine tone would reduce delay discounting in PPG subjects in proportion to its ability to augment top-down control. To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. In this subject population, we found that greater BOLD activity during the placebo condition within the right inferior frontal cortex (RIFC, a region thought to be important for inhibitory control, correlated with greater declines in impulsivity on tolcapone versus placebo. Intriguingly, connectivity between RIFC and the right striatum, and not the level of activity within RIFC itself, increased on tolcapone versus placebo. Together, these findings support the hypothesis that tolcapone-mediated increases in top-down control may reduce impulsivity in PPG subjects, a finding with potential translational relevance for gambling disorders, and for behavioral addictions in general.

  17. Reduced frontal cortex thickness and cortical volume associated with pathological narcissism.

    Science.gov (United States)

    Mao, Yu; Sang, Na; Wang, Yongchao; Hou, Xin; Huang, Hui; Wei, Dongtao; Zhang, Jinfu; Qiu, Jiang

    2016-07-22

    Pathological narcissism is often characterized by arrogant behavior, a lack of empathy, and willingness to exploit other individuals. Generally, individuals with high levels of narcissism are more likely to suffer mental disorders. However, the brain structural basis of individual pathological narcissism trait among healthy people has not yet been investigated with surface-based morphometry. Thus, in this study, we investigated the relationship between cortical thickness (CT), cortical volume (CV), and individual pathological narcissism in a large healthy sample of 176 college students. Multiple regression was used to analyze the correlation between regional CT, CV, and the total Pathological Narcissism Inventory (PNI) score, adjusting for age, sex, and total intracranial volume. The results showed that the PNI score was significantly negatively associated with CT and CV in the right dorsolateral prefrontal cortex (DLPFC, key region of the central executive network, CEN), which might be associated with impaired emotion regulation processes. Furthermore, the PNI score showed significant negative associations with CV in the right postcentral gyrus, left medial prefrontal cortex (MPFC), and the CT in the right inferior frontal cortex (IFG, overlap with social brain network), which may be related to impairments in social cognition. Together, these findings suggest a unique structural basis for individual differences in pathological narcissism, distributed across different gray matter regions of the social brain network and CEN. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. [Functional asymmetry of the frontal cortex and lateral hypothalamus of cats during food instrumental conditioning].

    Science.gov (United States)

    Vanetsiian, G L; Pavlova, I V

    2003-01-01

    The synchronism and latency of auditory evoked potentials (EP) recorded in symmetric points of the frontal cortex and lateral hypothalamus of cats were measured at different stages of instrumental food conditioning and after the urgent transition to 30% reinforcement. Correlation coefficients between EPs in the cortex and hypothalamus were high (with left-side dominance) at the beginning of the experiments, when food motivation was high, and during the whole experiments in cases of high-probability of conditioned performance. Analysis of early positive P55-80 EP component showed that at all conditioning stages the peak latency of this component was shorter in the left cortical areas than in symmetrical points, whereas in the hypothalamus the shorter latency at the left side was observed at the stage of unstable conditioned reflex, and at the stage of stable reflex the latency of the studied component was shorter at the right side. During transition to 30% reinforcement, the latency was also shorter in the right hypothalamus. It is suggested that the high left-side correlation between the hypothalamus and cortex was associated with motivational and motor component of behavior rather than reflected the emotional stress induced by transition to another stereotype of food reinforcement (30%).

  19. Role of the left frontal aslant tract in stuttering: a brain stimulation and tractographic study.

    Science.gov (United States)

    Kemerdere, Rahsan; de Champfleur, Nicolas Menjot; Deverdun, Jérémy; Cochereau, Jérôme; Moritz-Gasser, Sylvie; Herbet, Guillaume; Duffau, Hugues

    2016-01-01

    The neural correlates of stuttering are to date incompletely understood. Although the possible involvement of the basal ganglia, the cerebellum and certain parts of the cerebral cortex in this speech disorder has previously been reported, there are still not many studies investigating the role of white matter fibers in stuttering. Axonal stimulation during awake surgery provides a unique opportunity to study the functional role of structural connectivity. Here, our goal was to investigate the white matter tracts implicated in stuttering, by combining direct electrostimulation mapping and postoperative tractography imaging, with a special focus on the left frontal aslant tract. Eight patients with no preoperative stuttering underwent awake surgery for a left frontal low-grade glioma. Intraoperative cortical and axonal electrical mapping was used to interfere in speech processing and subsequently provoke stuttering. We further assessed the relationship between the subcortical sites leading to stuttering and the spatial course of the frontal aslant tract. All patients experienced intraoperative stuttering during axonal electrostimulation. On postsurgical tractographies, the subcortical distribution of stimulated sites matched the topographical position of the left frontal aslant tract. This white matter pathway was preserved during surgery, and no patients had postoperative stuttering. For the first time to our knowledge, by using direct axonal stimulation combined with postoperative tractography, we provide original data supporting a pivotal role of the left frontal aslant tract in stuttering. We propose that this speech disorder could be the result of a disconnection within a large-scale cortico-subcortical circuit subserving speech motor control.

  20. Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus.

    Science.gov (United States)

    Nishioka, G; Yamada, M; Kudo, K; Takahashi, K; Kiuchi, Y; Higuchi, T; Momose, K; Kamijima, K; Yamada, M

    2003-03-01

    It has been proposed that signaling pathways involved in adaptive neural plasticity are long-term targets for the action of electroconvulsive treatment (ECT), which is widely used in the treatment of drug-resistant depression. We have previously performed EST analysis to identify some molecular machinery responsible for antidepressant effect. One of the cDNA fragments identified as antidepressant related genes/ESTs was identified as kf-1 which has a RING-H2 finger motif at the carboxy-terminus. In the present study, we have demonstrated the induction of kf-1 in rat frontal cortex and hippocampus not only after chronic antidepressant treatment, but also after a single and repeated ECT. RING finger proteins are proposed to play some important roles in the ubiquitin-proteasome system. In conclusion, the current investigation has identified kf-1 as a novel molecular target for antidepressants and ECT.

  1. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases

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    Silvia Vanni

    2018-01-01

    Full Text Available Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively and in different genetic forms of prion diseases (gPrD in comparison to Alzheimer's disease (AD subjects and age-matched controls.Methods: Total RNA was obtained from the frontal cortex of vCJD (n = 20, iCJD (n = 11, sCJD (n = 23, gPrD (n = 30, and AD (n = 14 patients and age-matched controls (n = 30. RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis.Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level.Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue—together with specific molecular and conformational features of the pathological agent of the disease—seem to dictate the peculiar

  2. Apolipoprotein-E forms dimers in human frontal cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Halliday Glenda M

    2010-02-01

    Full Text Available Abstract Background Apolipoprotein-E (apoE plays important roles in neurobiology and the apoE4 isoform increases risk for Alzheimer's disease (AD. ApoE3 and apoE2 are known to form disulphide-linked dimers in plasma and cerebrospinal fluid whereas apoE4 cannot form these dimers as it lacks a cysteine residue. Previous in vitro research indicates dimerisation of apoE3 has a significant impact on its functions related to cholesterol homeostasis and amyloid-beta peptide degradation. The possible occurrence of apoE dimers in cortical tissues has not been examined and was therefore assessed. Human frontal cortex and hippocampus from control and AD post-mortem samples were homogenised and analysed for apoE by western blotting under both reducing and non-reducing conditions. Results In apoE3 homozygous samples, ~12% of apoE was present as a homodimer and ~2% was detected as a 43 kDa heterodimer. The level of dimerisation was not significantly different when control and AD samples were compared. As expected, these dimerised forms of apoE were not detected in apoE4 homozygous samples but were detected in apoE3/4 heterozygotes at a level approximately 60% lower than seen in the apoE3 homozygous samples. Similar apoE3 dimers were also detected in lysates of SK-N-SH neuroblastoma cells and in freshly prepared rabbit brain homogenates. The addition of the thiol trapping agent, iodoacetamide, to block reactive thiols during both human and rabbit brain sample homogenisation and processing did not reduce the amount of apoE homodimer recovered. These data indicate that the apoE dimers we detected in the human brain are not likely to be post-mortem artefacts. Conclusion The identification of disulphide-linked apoE dimers in human cortical and hippocampal tissues represents a distinct structural difference between the apoE3 and apoE4 isoforms that may have functional consequences.

  3. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

    2018-01-01

    Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

  4. Frontal Motor Cortex Activity During Reactive Control Is Associated With Past Suicidal Behavior in Recent-Onset Schizophrenia.

    Science.gov (United States)

    Minzenberg, Michael J; Lesh, Tyler; Niendam, Tara; Yoon, Jong H; Cheng, Yaoan; Rhoades, Remy N; Carter, Cameron S

    2015-01-01

    Suicide is prevalent in schizophrenia (SZ), yet the neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in SZ, including those that support reactive control, and PFC changes are observed in postmortem studies of heterogeneous suicide victims. We tested whether history of suicide attempt is associated with altered frontal motor cortex activity during reactive control processes. We evaluated 17 patients with recent onset of DSM-IV-TR-defined SZ using the Columbia Suicide Severity Rating Scale and functional magnetic resonance imaging during Stroop task performance. Group-level regression models relating past suicidal behavior to frontal activation controlled for depression, psychosis, and impulsivity. Past suicidal behavior was associated with relatively higher activation in the left-hemisphere supplementary motor area (SMA), pre-SMA, premotor cortex, and dorsolateral PFC, all ipsilateral to the active primary motor cortex. This study provides unique evidence that suicidal behavior in patients with recent-onset SZ directly relates to frontal motor cortex activity during reactive control, in a pattern reciprocal to the relationship with proactive control found previously. Further work should address how frontal-based control functions change with risk over time, and their potential utility as a biomarker for interventions to mitigate suicide risk in SZ.

  5. Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex

    DEFF Research Database (Denmark)

    Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z

    2017-01-01

    The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater...... degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during...... a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal...

  6. The morphology of midcingulate cortex predicts frontal-midline theta neurofeedback success

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    Stefanie eEnriquez-Geppert

    2013-08-01

    Full Text Available Humans differ in their ability to learn how to control their own brain activity by neurofeedback. However, neural mechanisms underlying these inter-individual differences, which may determine training success and associated cognitive enhancement, are not well understood. Here, it is asked whether neurofeedback success of frontal-midline (fm theta, an oscillation related to higher cognitive functions, could be predicted by the morphology of brain structures known to be critically involved in fm-theta generation. Nineteen young, right-handed participants underwent magnetic resonance imaging of T1-weighted brain images, and took part in an individualized, eight-session neurofeedback training in order to learn how to enhance activity in their fm-theta frequency band. Initial training success, measured at the second training session, was correlated with the final outcome measure. We found that the inferior, superior and middle frontal cortices were not associated with training success. However, volume of the midcingulate cortex as well as volume and concentration of the underlying white matter structures act as predictor variables for the general responsiveness to training. These findings suggest a neuroanatomical foundation for the ability to learn to control one’s own brain activity.

  7. Chronic Ritalin administration during adulthood increases serotonin pool in rat medial frontal cortex.

    Science.gov (United States)

    Daniali, Samira; Madjd, Zahra; Shahbazi, Ali; Niknazar, Somayeh; Shahbazzadeh, Delavar

    2013-01-01

    Ritalin has high tendency to be abused. It has been the main indication to control attention deficit hyperactivity disorder. The college students may seek for it to improve their memory, decrease the need for sleep (especially during exams), which at least partially, can be related to serotonergic system. Therefore, it seems worthy to evaluate the effect of Ritalin intake on mature brain. There are many studies on Ritalin effect on developing brain, but only few studies on adults are available. This study was undertaken to find Ritalin effect on serotonin transporter (SERT) density in medial frontal cortex (MFC) of mature rat. Thirty male Wistar rats were used in the study. Rats were assigned into five groups (n = 6 per group): one control, two Ritalin and two vehicle groups. Twelve rats received Ritalin (20 mg/kg/twice a day) orally for eleven continuous days. After one week of withdrawal and another two weeks of rest, in order to evaluate short-term effects of Ritalin, six rats were sacrificed. Another six rats were studied to detect the long-term effects of Ritalin; therefore, they were sacrificed 12 weeks after the previous group. The immunohistochemistry was performed to evaluate the results. Immunohistochemistry studies showed a higher density of SERT in both 2 and 12 weeks after withdrawal from Ritalin intake in MFC of rat and there was no significant difference between these two groups. Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period.

  8. Lateral frontal cortex volume reduction in Tourette syndrome revealed by VBM

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    Wittfoth Matthias

    2012-02-01

    Full Text Available Abstract Background Structural changes have been found predominantly in the frontal cortex and in the striatum in children and adolescents with Gilles de la Tourette syndrome (GTS. The influence of comorbid symptomatology is unclear. Here we sought to address the question of gray matter abnormalities in GTS patients with co-morbid obsessive-compulsive disorder (OCD and/or attention deficit hyperactivity disorder (ADHD using voxel-based morphometry (VBM in twenty-nine adult actually unmedicated GTS patients and twenty-five healthy control subjects. Results In GTS we detected a cluster of decreased gray matter volume in the left inferior frontal gyrus (IFG, but no regions demonstrating volume increases. By comparing subgroups of GTS with comorbid ADHD to the subgroup with comorbid OCD, we found a left-sided amygdalar volume increase. Conclusions From our results it is suggested that the left IFG may constitute a common underlying structural correlate of GTS with co-morbid OCD/ADHD. A volume reduction in this brain region that has been previously identified as a key region in OCD and was associated with the active inhibition of attentional processes may reflect the failure to control behavior. Amygdala volume increase is discussed on the background of a linkage of this structure with ADHD symptomatology. Correlations with clinical data revealed gray matter volume changes in specific brain areas that have been described in these conditions each.

  9. Social Function in Boys with Cleft Lip and Palate: Relationship to Ventral Frontal Cortex Morphology

    Science.gov (United States)

    Boes, Aaron D.; Murko, Vesna; Wood, Jessica L.; Langbehn, Douglas R.; Canady, John; Richman, Lynn; Nopoulos, Peg

    2007-01-01

    Isolated clefts of the lip and/or palate (ICLP) are developmental craniofacial abnormalities that have consistently been linked to increased social inhibition or shyness. Two explanations have been proposed: 1) psychosocial factors related to differences in facial appearance may lead to low self-concept and subsequent shyness, or 2) abnormal development of brain structures involved in social function, such as the ventral frontal cortex (VFC), may underlie the difference. To investigate these two possibilities this study was designed to evaluate measures of social function in relation to measures of self-concept and VFC morphology. Subjects included 30 boys (age 7-12) with ICLP and a comparison group of 43 boys without cleft in the same age category. Social function and self-concept were assessed using questionnaires with standardized scoring filled out by subjects and one of their parents. The cortical volume and surface area of the VFC, composed of the orbitofrontal cortex (OFC) and straight gyrus (SG), were evaluated using structural magnetic resonance imaging. The ICLP subjects had significantly impaired social function relative to the comparison group. No difference in self-concept was identified. VFC morphology revealed significant differences between groups, particularly decreased volume and surface area in the left SG of the ICLP group. Moreover, abnormal VFC measures were correlated with social dysfunction but measures of self-concept were not. These results are consistent with the possibility that aberrant VFC development may partially underlie social dysfunction in boys with ICLP. PMID:17537526

  10. Chronic consumption of a western diet modifies the DNA methylation profile in the frontal cortex of mice.

    Science.gov (United States)

    Yokoyama, Amy S; Dunaway, Keith; Rutkowsky, Jennifer; Rutledge, John C; Milenkovic, Dragan

    2018-02-21

    In our previous work in mice, we have shown that chronic consumption of a Western diet (WD; 42% kcal fat, 0.2% total cholesterol and 34% sucrose) is correlated with impaired cognitive function. Cognitive decline has also been associated with alterations in DNA methylation. Additionally, although there have been many studies analyzing the effect of maternal consumption of a WD on DNA methylation in the offspring, few studies have analyzed how an individual's consumption of a WD can impact his/her DNA methylation. Since the frontal cortex is involved in the regulation of cognitive function and is often affected in cases of cognitive decline, this study aimed to examine how chronic consumption of a WD affects DNA methylation in the frontal cortex of mice. Eight-week-old male mice were fed either a control diet (CD) or a WD for 12 weeks, after which time alterations in DNA methylation were analyzed. Assessment of global DNA methylation in the frontal cortex using dot blot analysis revealed that there was a decrease in global DNA methylation in the WD-fed mice compared with the CD-fed mice. Bioinformatic analysis identified several networks and pathways containing genes displaying differential methylation, particularly those involved in metabolism, cell adhesion and cytoskeleton integrity, inflammation and neurological function. In conclusion, the results from this study suggest that consumption of a WD alters DNA methylation in the frontal cortex of mice and could provide one of the mechanisms by which consumption of a WD impairs cognitive function.

  11. Local-circuit phenotypes of layer 5 neurons in motor-frontal cortex of YFP-H mice

    Directory of Open Access Journals (Sweden)

    Jianing Yu

    2008-12-01

    Full Text Available Layer 5 pyramidal neurons comprise an important but heterogeneous group of cortical projection neurons. In motor-frontal cortex, these neurons are centrally involved in the cortical control of movement. Recent studies indicate that local excitatory networks in mouse motor-frontal cortex are dominated by descending pathways from layer 2/3 to 5. However, those pathways were identified in experiments involving unlabeled neurons in wild type mice. Here, to explore the possibility of class-specific connectivity in this descending pathway, we mapped the local sources of excitatory synaptic input to a genetically labeled population of cortical neurons: YFP-positive layer 5 neurons of YFP-H mice. We found, first, that in motor cortex, YFP-positive neurons were distributed in a double blade, consistent with the idea of layer 5B having greater thickness in frontal neocortex. Second, whereas unlabeled neurons in upper layer 5 received their strongest inputs from layer 2, YFP-positive neurons in the upper blade received prominent layer 3 inputs. Third, YFP-positive neurons exhibited distinct electrophysiological properties, including low spike frequency adaptation, as reported previously. Our results with this genetically labeled neuronal population indicate the presence of distinct local-circuit phenotypes among layer 5 pyramidal neurons in mouse motor-frontal cortex, and present a paradigm for investigating local circuit organization in other genetically labeled populations of cortical neurons.

  12. GABAA receptor B subunit expression in the superior frontal cortex of human alcoholics

    International Nuclear Information System (INIS)

    Buckley, S.T.; Dodd, P.R.

    2001-01-01

    Full text: Changes in GABA A receptor pharmacology can be ascribed to alterations in expression of specific GABA A receptor subunits. Ethanol is known to be a potent agonist of the GABA A receptor. Chronic abuse of alcohol in humans results in damage of selective brain regions such as the superior frontal cortex (SFC), leading to neuronal cell loss. Studies in our laboratory 1 and elsewhere 2 have shown differences in expression of a number of GABA A receptor subunits in chronic human alcoholism. This suggests that alterations in GABA A receptor composition may be involved in the pathogenesis of alcoholic brain damage. We analysed the expression of the β 1 ,β 2 and β 3 isoforms of the GABA A receptor by a competitive reverse transcription polymerase chain reaction (RT-PCR) technique, which utilised an internal standard (IS) for quantitation. 35 S-dATP was incorporated to enable visualisation of the PCR products. Human brain tissue was obtained at autopsy and stored in 0.32 M sucrose at -80 deg C. Total RNA was extracted from pathologically susceptible and spared regions, SFC and motor cortex respectively,of 22 control and 22 alcoholic patients. 1 μg of total RNA from each sample was co-amplified with 0.5 pg of IS and a ratio determined. A standard consisting of known amounts of β 1 cRNA titrated against 0.5 pg of IS enabled a standard curve to be generated for quantitation of each unknown sample. The samples were subjected to polyacrylamide gel electrophoresis and the dried gel exposed to a phosphorimager screen. Data analysis was performed using the ImageQuant program. Initial results indicate that there is a reduction in expression of all the β transcripts in alcoholics when compared with controls, which supports the hypothesis that the GABA A receptor is altered by alcohol abuse. Supported by NHMRC. Copyright (2001) Australian Neuroscience Society

  13. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    Science.gov (United States)

    Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

    2016-01-01

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

  14. Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type

    Directory of Open Access Journals (Sweden)

    Ravi Rajmohan

    2017-05-01

    Full Text Available Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT through the use of the sex determination test (SDT. In the current study, four (1 female, 3 males CDDAT and nine (4 females, 5 males age-matched neurotypicals (NT completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA and anterior cingulate cortex (ACC. DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC, but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability.

  15. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    Science.gov (United States)

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  16. Inferior Frontal Cortex Contributions to the Recognition of Spoken Words and Their Constituent Speech Sounds.

    Science.gov (United States)

    Rogers, Jack C; Davis, Matthew H

    2017-05-01

    Speech perception and comprehension are often challenged by the need to recognize speech sounds that are degraded or ambiguous. Here, we explore the cognitive and neural mechanisms involved in resolving ambiguity in the identity of speech sounds using syllables that contain ambiguous phonetic segments (e.g., intermediate sounds between /b/ and /g/ as in "blade" and "glade"). We used an audio-morphing procedure to create a large set of natural sounding minimal pairs that contain phonetically ambiguous onset or offset consonants (differing in place, manner, or voicing). These ambiguous segments occurred in different lexical contexts (i.e., in words or pseudowords, such as blade-glade or blem-glem) and in different phonological environments (i.e., with neighboring syllables that differed in lexical status, such as blouse-glouse). These stimuli allowed us to explore the impact of phonetic ambiguity on the speed and accuracy of lexical decision responses (Experiment 1), semantic categorization responses (Experiment 2), and the magnitude of BOLD fMRI responses during attentive comprehension (Experiment 3). For both behavioral and neural measures, observed effects of phonetic ambiguity were influenced by lexical context leading to slower responses and increased activity in the left inferior frontal gyrus for high-ambiguity syllables that distinguish pairs of words, but not for equivalent pseudowords. These findings suggest lexical involvement in the resolution of phonetic ambiguity. Implications for speech perception and the role of inferior frontal regions are discussed.

  17. Repressive Epigenetic Changes at the mGlu2 Promoter in Frontal Cortex of 5-HT2A Knockout Mice

    Science.gov (United States)

    Kurita, Mitsumasa; Moreno, José L.; Holloway, Terrell; Kozlenkov, Alexey; Mocci, Giuseppe; García-Bea, Aintzane; Hanks, James B.; Neve, Rachael; Nestler, Eric J.; Russo, Scott J.

    2013-01-01

    Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are G protein–coupled receptors suspected in the pathophysiology of psychiatric disorders, such as schizophrenia, depression, and suicide. Previous findings demonstrate that mGlu2 mRNA expression is down-regulated in brain cortical regions of 5-HT2A knockout (KO) mice. However, the molecular mechanism responsible for this alteration remains unknown. We show here repressive epigenetic changes at the promoter region of the mGlu2 gene in frontal cortex of 5-HT2A-KO mice. Disruption of 5-HT2A receptor-dependent signaling in mice was associated with decreased acetylation of histone H3 (H3ac) and H4 (H4ac) and increased tri-methylation of histone H3 at lysine 27 (H3K27me3) at the mGlu2 promoter, epigenetic changes that correlate with transcriptional repression. Neither methylation of histone H3 at lysine 4 (H3K4me1/2/3) nor tri-methylation of histone H3 at lysine 9 (H3K9me3) was affected. We found that Egr1, a transcription factor in which promoter activity was positively regulated by the 5-HT2A receptor agonist 4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide, binds less to the mGlu2 promoter in frontal cortex of 5-HT2A-KO, compared with wild-type mice. Furthermore, expression of mGlu2 was increased by viral-mediated gene transfer of FLAG-tagged Egr1 in mouse frontal cortex. Together, these observations suggest that 5-HT2A receptor–dependent signaling epigenetically affects mGlu2 transcription in mouse frontal cortex. PMID:23508685

  18. Dissociable contribution of the parietal and frontal cortex to coding movement direction and amplitude

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    Marco eDavare

    2015-05-01

    Full Text Available To reach for an object, we must convert its spatial location into an appropriate motor command, merging movement direction and amplitude. In humans, it has been suggested that this visuo-motor transformation occurs in a dorsomedial parieto-frontal pathway, although the causal contribution of the areas constituting the reaching circuit remains unknown. Here we used transcranial magnetic stimulation (TMS in healthy volunteers to disrupt the function of either the medial intraparietal area (mIPS or dorsal premotor cortex (PMd, in each hemisphere. The task consisted in performing step-tracking movements with the right wrist towards targets located in different directions and eccentricities; the targets were either visible for the whole trial (Target-ON or flashed for 200 ms (Target-OFF. Left and right mIPS disruption led to errors in the initial direction of movements performed towards contralateral targets. These errors were corrected online in the Target-ON condition but when the target was flashed for 200 ms, mIPS TMS manifested as a larger endpoint spreading. In contrast, left PMd virtual lesions led to higher acceleration and velocity peaks - two parameters typically used to probe the planned movement amplitude - irrespective of the target position, hemifield and presentation condition; in the Target-OFF condition, left PMd TMS induced overshooting and increased the endpoint dispersion along the axis of the target direction. These results indicate that left PMd intervenes in coding amplitude during movement preparation. The critical TMS timings leading to errors in direction and amplitude were different, namely 160-100 ms before movement onset for mIPS and 100-40 ms for left PMd. TMS applied over right PMd had no significant effect. These results indicate that, during motor preparation, direction and amplitude of goal-directed movements are processed by different cortical areas, at distinct timings, and according to a specific hemispheric

  19. New model of action for mood stabilizers: phosphoproteome from rat pre-frontal cortex synaptoneurosomal preparations.

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    Maria Corena-McLeod

    Full Text Available BACKGROUND: Mitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level. HYPOTHESIS: Mitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement. METHODS: Synaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry. RESULTS: Lithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation. CONCLUSIONS: Mood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights

  20. Role of the lateral prefrontal cortex in speech monitoring

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    Stephanie K. Riès

    2013-10-01

    Full Text Available The role of lateral prefrontal cortex in speech monitoring has not been delineated. Recent work suggests that medial frontal cortex (MFC is involved in overt speech monitoring initiated before auditory feedback. This mechanism is reflected in an event-related potential (ERP, the error negativity (Ne, peaking within 100 ms after vocal-onset. Critically, in healthy individuals the Ne is sensitive to the accuracy of the response; it is larger for error than correct trials. By contrast, patients with lateral prefrontal cortex (lPFC damage are impaired in nonverbal monitoring tasks showing no amplitude difference between the Ne measured in correct vs. error trials. Interactions between the lPFC and the MFC are assumed to play a necessary role for normal action monitoring. We investigated whether the lPFC was involved in speech monitoring to the same extent as in non-linguistic actions by comparing performance and EEG activity in patients with lPFC damage and in aged-matched controls performing linguistic (Picture Naming and non-linguistic (Simon tasks. Controls did not produce enough errors to allow the comparison of the Ne or other ERP in error vs. correct trials. PFC patients had worse performance than controls in both tasks, but their Ne was larger for error than correct trials only in Naming. This task-dependent pattern can be explained by lPFC-dependent working-memory requirements present in non-linguistic tasks used to study action monitoring but absent in picture naming. This suggests that lPFC may not be necessary for speech monitoring as assessed by simple picture naming. In addition, bilateral temporal cortex activity starting before and peaking around vocal-onset was observed in lPFC and control groups in both tasks but was larger for error than correct trials only in Naming, suggesting the temporal cortex is associated with on-line monitoring of speech specifically when access to lexical representations is necessary.

  1. Transcranial Magnetic Stimulation over Left Inferior Frontal and Posterior Temporal Cortex Disrupts Gesture-Speech Integration.

    Science.gov (United States)

    Zhao, Wanying; Riggs, Kevin; Schindler, Igor; Holle, Henning

    2018-02-21

    Language and action naturally occur together in the form of cospeech gestures, and there is now convincing evidence that listeners display a strong tendency to integrate semantic information from both domains during comprehension. A contentious question, however, has been which brain areas are causally involved in this integration process. In previous neuroimaging studies, left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) have emerged as candidate areas; however, it is currently not clear whether these areas are causally or merely epiphenomenally involved in gesture-speech integration. In the present series of experiments, we directly tested for a potential critical role of IFG and pMTG by observing the effect of disrupting activity in these areas using transcranial magnetic stimulation in a mixed gender sample of healthy human volunteers. The outcome measure was performance on a Stroop-like gesture task (Kelly et al., 2010a), which provides a behavioral index of gesture-speech integration. Our results provide clear evidence that disrupting activity in IFG and pMTG selectively impairs gesture-speech integration, suggesting that both areas are causally involved in the process. These findings are consistent with the idea that these areas play a joint role in gesture-speech integration, with IFG regulating strategic semantic access via top-down signals acting upon temporal storage areas. SIGNIFICANCE STATEMENT Previous neuroimaging studies suggest an involvement of inferior frontal gyrus and posterior middle temporal gyrus in gesture-speech integration, but findings have been mixed and due to methodological constraints did not allow inferences of causality. By adopting a virtual lesion approach involving transcranial magnetic stimulation, the present study provides clear evidence that both areas are causally involved in combining semantic information arising from gesture and speech. These findings support the view that, rather than being

  2. The Effect of Retrieval Focus and Emotional Valence on the Inferior Frontal Cortex Activity during Autobiographical Recollection

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    Ekaterina eDenkova

    2013-12-01

    Full Text Available Although available evidence points to a role of the inferior frontal cortex (IFC in both emotion processing and autobiographical memory (AM recollection, it is unclear what the role of this region is in emotional AMs recollection. The present study investigated whether IFC activity can be influenced by manipulations of the retrieval focus (emotional vs. non-emotional and whether this influence is similar for AMs with positive and negative emotional valence. Participants were asked to focus either on emotional (Emotion condition or on non-emotional contextual (Context condition details during the elaboration of positive and negative AMs, while fMRI data were collected. The study yielded two main findings: (1 Focusing on emotion compared to context during AMs recollection was associated with increased activity in bilateral IFC, for positive AMs, whereas negative AMs produced similarly high IFC activity during Emotion and Context conditions; (2 There was a hemispheric dissociation in the IFC linked to the experiencing of emotion and the focus of AM Recollection, such that the left IFC activity correlated positively with the subjective re-experience of emotion during the Emotion condition, whereas the right IFC activity correlated negatively with the subjective re-experience of emotion during the Context condition, for both positive and negative AMs. Overall, the present findings suggest that IFC’s involvement during the recollection of emotional AMs is susceptible to manipulations of the retrieval focus only in the case of positive AMs, and that this region plays a role in both the enhancement and inhibition of emotional experience during AM recollection.

  3. Regional concentrations of noradrenaline and dopamine in the frontal cortex of the rat: dopaminergic innervation of the prefrontal subareas and lateralization of prefrontal dopamine

    NARCIS (Netherlands)

    Slopsema, J.S.; Gugten, J. van der; Bruin, J.P.C. de

    1982-01-01

    Catecholamine levels in the two subareas of the prefrontal cortex and in one non-prefrontal region of the rat frontal lobe were measured radioenzymatically. In contrast with noradrenaline (NA), the distribution of dopamine (DA) in the frontal lobe is markedly heterogeneous. DA levels of the

  4. Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

    Science.gov (United States)

    Matsuoka, Kiwamu; Yasuno, Fumihiko; Hashimoto, Akiko; Miyasaka, Toshiteru; Takahashi, Masato; Kiuchi, Kuniaki; Iida, Junzo; Kichikawa, Kimihiko; Kishimoto, Toshifumi

    2017-12-27

    Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden. Copyright © 2017 John Wiley & Sons, Ltd.

  5. The left frontal cortex supports reserve in aging by enhancing functional network efficiency.

    Science.gov (United States)

    Franzmeier, Nicolai; Hartmann, Julia; Taylor, Alexander N W; Araque-Caballero, Miguel Á; Simon-Vermot, Lee; Kambeitz-Ilankovic, Lana; Bürger, Katharina; Catak, Cihan; Janowitz, Daniel; Müller, Claudia; Ertl-Wagner, Birgit; Stahl, Robert; Dichgans, Martin; Duering, Marco; Ewers, Michael

    2018-03-06

    Recent evidence derived from functional magnetic resonance imaging (fMRI) studies suggests that functional hubs (i.e., highly connected brain regions) are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer's disease. These results suggest that LFC connectivity supports reserve capacity, alleviating memory decline. An open question, however, is why LFC connectivity is beneficial and supports memory function in the face of neurodegeneration. We hypothesized that higher LFC connectivity is associated with enhanced efficiency in connected major networks involved in episodic memory. We further hypothesized that higher LFC-related network efficiency predicts higher memory abilities. We assessed fMRI during a face-name association learning task performed by 26 healthy, cognitively normal elderly participants. Using beta-series correlation analysis, we computed task-related LFC connectivity to key memory networks, including the default mode network (DMN) and dorsal attention network (DAN). Network efficiency within the DMN and DAN was estimated by the graph theoretical small-worldness statistic. We applied linear regression analyses to test the association between LFC connectivity with the DMN/DAN and small-worldness of these networks. Mediation analysis was applied to test LFC connectivity to the DMN and DAN as a mediator of the association between education and higher DMN and DAN small-worldness. Last, we tested network small-worldness as a predictor of memory performance. We found that higher LFC connectivity to the DMN and DAN during successful memory encoding and recognition was associated with higher small-worldness of those networks. Higher task-related LFC connectivity mediated the association between education and higher small-worldness in the DMN

  6. Effects of Hypothyroidism on Expression of CRMP2B and ARPC5 during Development of the Rat Frontal Cortex

    Science.gov (United States)

    Liu, Chun-rong; Miao, Jun; Zhang, Yong-liang; Liu, Ya-min; Yu, Bao-guo

    2013-01-01

    Congenital hypothyroidism (CH) can lead to irreversible central nervous system (CNS) damage. However, the pathogenesis of the developmental brain disorders caused by CH has not been completely elucidated. ARPC5 and CRMP2 are closely associated with neurite outgrowth in brain development. Thus, the aim of the present study was to determine whether CRMP2B and ARPC5 expression is altered in the developing cerebral cortex of rats with CH. Control rats and rats with hypothyroidism were sacrificed at birth and at 15 days postpartum. We performed qRT-PCR to detect differences in the crmp2B and arpc5 mRNA expression in the right half of the frontal cortex of these rats. Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression. Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5. Results showed increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism. These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B. CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization. PMID:23459330

  7. The congruency effect in the posterior medial frontal cortex is more consistent with time on task than with response conflict.

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    Daniel H Weissman

    Full Text Available The posterior medial frontal cortex (pMFC is thought to play a pivotal role in enabling the control of attention during periods of distraction. In line with this view, pMFC activity is ubiquitously greater in incongruent trials of response-interference (e.g., Stroop tasks than in congruent trials. Nonetheless, the process underlying this congruency effect remains highly controversial. We therefore sought to distinguish between two competing accounts of the congruency effect. The conflict monitoring account posits the effect indexes a process that detects conflict between competing response alternatives, which is indexed by trial-specific reaction time (RT. The time on task account posits the effect indexes a process whose recruitment increases with time on task independent of response conflict (e.g., sustained attention, arousal, effort, etc.. To distinguish between these accounts, we used functional MRI to record brain activity in twenty-four healthy adults while they performed two tasks: a response-interference task and a simple RT task with only one possible response. We reasoned that demands on a process that detects response conflict should increase with RT in the response-interference task but not in the simple RT task. In contrast, demands on a process whose recruitment increases with time on task independent of response conflict should increase with RT in both tasks. Trial-by-trial analyses revealed that pMFC activity increased with RT in both tasks. Moreover, pMFC activity increased with RT in the simple RT task enough to fully account for the congruency effect in the response-interference task. These findings appear more consistent with the time on task account of the congruency effect than with the conflict monitoring account.

  8. A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields.

    Science.gov (United States)

    Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

    2016-09-06

    Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas.

  9. The galanin receptor agonist, galnon, attenuates cocaine-induced reinstatement and dopamine overflow in the frontal cortex.

    Science.gov (United States)

    Ogbonmwan, Yvonne E; Sciolino, Natale R; Groves-Chapman, Jessica L; Freeman, Kimberly G; Schroeder, Jason P; Edwards, Gaylen L; Holmes, Philip V; Weinshenker, David

    2015-07-01

    Relapse represents one of the most significant problems in the long-term treatment of drug addiction. Cocaine blocks plasma membrane monoamine transporters and increases dopamine (DA) overflow in the brain, and DA is critical for the motivational and primary reinforcing effects of the drug as well as cocaine-primed reinstatement of cocaine seeking in rats, a model of relapse. Thus, modulators of the DA system may be effective for the treatment of cocaine dependence. The endogenous neuropeptide galanin inhibits DA transmission, and both galanin and the synthetic galanin receptor agonist, galnon, interfere with some rewarding properties of cocaine. The purpose of this study was to further assess the effects of galnon on cocaine-induced behaviors and neurochemistry in rats. We found that galnon attenuated cocaine-induced motor activity, reinstatement and DA overflow in the frontal cortex at a dose that did not reduce baseline motor activity, stable self-administration of cocaine, baseline extracellular DA levels or cocaine-induced DA overflow in the nucleus accumbens (NAc). Similar to cocaine, galnon had no effect on stable food self-administration but reduced food-primed reinstatement. These results indicate that galnon can diminish cocaine-induced hyperactivity and relapse-like behavior, possibly in part by modulating DA transmission in the frontal cortex. © 2014 Society for the Study of Addiction.

  10. High-alpha band synchronization across frontal, parietal and visual cortex mediates behavioral and neuronal effects of visuospatial attention.

    Science.gov (United States)

    Lobier, Muriel; Palva, J Matias; Palva, Satu

    2018-01-15

    Visuospatial attention prioritizes processing of attended visual stimuli. It is characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual cortex and increased neuronal activity in a network of frontal and parietal areas. It has remained unknown what mechanisms coordinate neuronal processing among frontoparietal network and visual cortices and implement the attention-related modulations of alpha-band amplitudes and behavior. We investigated whether large-scale network synchronization could be such a mechanism. We recorded human cortical activity with magnetoencephalography (MEG) during a visuospatial attention task. We then identified the frequencies and anatomical networks of inter-areal phase synchronization from source localized MEG data. We found that visuospatial attention is associated with robust and sustained long-range synchronization of cortical oscillations exclusively in the high-alpha (10-14 Hz) frequency band. This synchronization connected frontal, parietal and visual regions and was observed concurrently with amplitude suppression of low-alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high-alpha phase synchronization was associated with decreased reaction times to attended stimuli and larger suppression of alpha-band amplitudes. These results thus show that high-alpha band phase synchronization is functionally significant and could coordinate the neuronal communication underlying the implementation of visuospatial attention. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The role of prefrontal cortex in psychopathy

    Science.gov (United States)

    Koenigs, Michael

    2014-01-01

    Psychopathy is a personality disorder characterized by remorseless and impulsive antisocial behavior. Given the significant societal costs of the recidivistic criminal activity associated with the disorder, there is a pressing need for more effective treatment strategies, and hence, a better understanding of the psychobiological mechanisms underlying the disorder. The prefrontal cortex (PFC) is likely to play an important role in psychopathy. In particular, the ventromedial and anterior cingulate sectors of PFC are theorized to mediate a number of social and affective decision-making functions that appear to be disrupted in psychopathy. This article provides a critical summary of human neuroimaging data implicating prefrontal dysfunction in psychopathy. A growing body of evidence associates psychopathy with structural and functional abnormalities in ventromedial PFC and anterior cingulate cortex. Although this burgeoning field still faces a number of methodological challenges and outstanding questions that will need to be resolved by future studies, the research to date has established a link between psychopathy and PFC. PMID:22752782

  12. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    Science.gov (United States)

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  13. The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

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    Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

    2017-12-01

    Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

  14. Issues in Localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

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    Gregory A. Miller

    2013-01-01

    Full Text Available The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left hemisphere. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

  15. Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

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    Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

    2017-02-22

    Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed

  16. Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

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    Averbeck, Bruno B.

    2017-01-01

    Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also

  17. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

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    Laura Musazzi

    2010-01-01

    Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

  18. Ventromedial frontal lobe plays a critical role in facial emotion recognition.

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    Heberlein, Andrea S; Padon, Alisa A; Gillihan, Seth J; Farah, Martha J; Fellows, Lesley K

    2008-04-01

    The ventromedial prefrontal cortex has been implicated in a variety of emotion processes. However, findings regarding the role of this region specifically in emotion recognition have been mixed. We used a sensitive facial emotion recognition task to compare the emotion recognition performance of 7 subjects with lesions confined to ventromedial prefrontal regions, 8 subjects with lesions elsewhere in prefrontal cortex, and 16 healthy control subjects. We found that emotion recognition was impaired following ventromedial, but not dorsal or lateral, prefrontal damage. This impairment appeared to be quite general, with lower overall ratings or more confusion between all six emotions examined. We also explored the relationship between emotion recognition performance and the ability of the same patients to experience transient happiness and sadness during a laboratory mood induction. We found some support for a relationship between sadness recognition and experience. Taken together, our results indicate that the ventromedial frontal lobe plays a crucial role in facial emotion recognition, and suggest that this deficit may be related to the subjective experience of emotion.

  19. Selective visual attention to emotional words: Early parallel frontal and visual activations followed by interactive effects in visual cortex.

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    Schindler, Sebastian; Kissler, Johanna

    2016-10-01

    Human brains spontaneously differentiate between various emotional and neutral stimuli, including written words whose emotional quality is symbolic. In the electroencephalogram (EEG), emotional-neutral processing differences are typically reflected in the early posterior negativity (EPN, 200-300 ms) and the late positive potential (LPP, 400-700 ms). These components are also enlarged by task-driven visual attention, supporting the assumption that emotional content naturally drives attention. Still, the spatio-temporal dynamics of interactions between emotional stimulus content and task-driven attention remain to be specified. Here, we examine this issue in visual word processing. Participants attended to negative, neutral, or positive nouns while high-density EEG was recorded. Emotional content and top-down attention both amplified the EPN component in parallel. On the LPP, by contrast, emotion and attention interacted: Explicit attention to emotional words led to a substantially larger amplitude increase than did explicit attention to neutral words. Source analysis revealed early parallel effects of emotion and attention in bilateral visual cortex and a later interaction of both in right visual cortex. Distinct effects of attention were found in inferior, middle and superior frontal, paracentral, and parietal areas, as well as in the anterior cingulate cortex (ACC). Results specify separate and shared mechanisms of emotion and attention at distinct processing stages. Hum Brain Mapp 37:3575-3587, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

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    Mahó Sándor

    2011-07-01

    Full Text Available Abstract Background Estrogens exert anti-inflammatory and neuroprotective effects in the brain mainly via estrogen receptors α (ERα and β (ERβ. These receptors are members of the nuclear receptor superfamily of ligand-dependent transcription factors. This study was aimed at the elucidation of the effects of ERα and ERβ agonists on the expression of neuroinflammatory genes in the frontal cortex of aging female rats. Methods To identify estrogen-responsive immunity/inflammation genes, we treated middle-aged, ovariectomized rats with 17β-estradiol (E2, ERα agonist 16α-lactone-estradiol (16α-LE2 and ERβ agonist diarylpropionitrile (DPN, or vehicle by Alzet minipump delivery for 29 days. Then we compared the transcriptomes of the frontal cortex of estrogen-deprived versus ER agonist-treated animals using Affymetrix Rat230 2.0 expression arrays and TaqMan-based quantitative real-time PCR. Microarray and PCR data were evaluated by using Bioconductor packages and the RealTime StatMiner software, respectively. Results Microarray analysis revealed the transcriptional regulation of 21 immunity/inflammation genes by 16α-LE2. The subsequent comparative real-time PCR study analyzed the isotype specific effects of ER agonists on neuroinflammatory genes of primarily glial origin. E2 regulated the expression of sixteen genes, including down-regulation of complement C3 and C4b, Ccl2, Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b, Cd11b, Tlr4 and Tlr9, and up-regulation of defensin Np4 and RatNP-3b, IgG-2a, Il6 and ER gene Esr1. Similar to E2, both 16α-LE2 and DPN evoked up-regulation of defensins, IgG-2a and Il6, and down-regulation of C3 and its receptor Cd11b, Ccl2, RT1-Aw2 and Fcgr2b. Conclusions These findings provide evidence that E2, 16α-LE2 and DPN modulate the expression of neuroinflammatory genes in the frontal cortex of middle-aged female rats via both ERα and ERβ. We propose that ERβ is a promising target to suppress

  1. The role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy.

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    Andrea eBecchetti

    2015-02-01

    Full Text Available Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE is a focal epilepsy with attacks typically arising in the frontal lobe during non rapid eye movement (NREM sleep. It is characterized by clusters of complex and stereotyped hypermotor seizures, frequently accompanied by sudden arousals. Cognitive and psychiatric symptoms may be also observed. Approximately 12% of the ADNFLE families carry mutations on genes coding for subunits of the heteromeric neuronal nicotinic receptors (nAChRs. This is consistent with the widespread expression of these receptors, particularly the α4β2* subtype, in the neocortex and thalamus. However, understanding how mutant nAChRs lead to partial frontal epilepsy is far from being straightforward because of the complexity of the cholinergic regulation in both developing and mature brains. The relation with the sleep-waking cycle must be also explained. We discuss some possible pathogenetic mechanisms in the light of recent advances about the nAChR role in prefrontal regions as well as the studies carried out in murine models of ADNFLE. Functional evidence points to alterations in prefrontal GABA release, and the synaptic unbalance probably arises during the cortical circuit maturation. Although most of the available functional evidence concerns mutations on nAChR subunit genes, other genes have been recently implicated in the disease, such as KCNT1 (coding for a Na+-dependent K+ channel, DEPD5 (Dishevelled, Egl-10 and Pleckstrin Domain-containing protein 5, and CRH (Corticotropin-Releasing Hormone. Overall, the uncertainties about both the etiology and the pathogenesis of ADNFLE point to the current gaps in our knowledge the regulation of neuronal networks in the cerebral cortex.

  2. The role of frontal and parietal brain areas in bistable perception

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    Knapen, T.; Brascamp, J.; Pearson, J.; van Ee, R.; Blake, R.

    2011-01-01

    When sensory input allows for multiple, competing perceptual interpretations, observers' perception can fluctuate over time, which is called bistable perception. Imaging studies in humans have revealed transient responses in a right-lateralized network in the frontal-parietal cortex (rFPC) around

  3. Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors.

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    Yamaguchi, T; Suzuki, M; Yamamoto, M

    1997-12-01

    Effects of indeloxazine hydrochloride, an inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake with a facilitatory effect on 5-HT release, on acetylcholine (ACh) output in frontal cortex of conscious rats were characterized using an in vivo microdialysis technique. Systemic administration of indeloxazine (3 and 10 mg/kg, i.p.) increased ACh and 5-HT output in a dose-dependent manner. Depletion of endogenous monoamines by reserpine and of 5-HT by p-chlorophenylalanine, but not that of catecholamines by alpha-methyl-p-tyrosine, significantly attenuated the facilitatory effect of indeloxazine on ACh release. When applied locally by reverse dialysis, indeloxazine (10 and 30 microM) and the selective 5-HT reuptake inhibitor citalopram (10 microM), but not the NE reuptake inhibitor maprotiline (30 microM), increased cortical ACh output. Indeloxazine (10 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (100 microM), 5-HT1A/1B/beta-adrenoceptor antagonist (-)propranolol (150 microM), 5-HT2A/2C antagonist ritanserin (10 microM) and 5-HT3 antagonist ondansetron (10 microM) failed to significantly modify this effect. Neither depletion of monoamines nor treatment with serotonergic antagonists significantly changed the basal ACh level, indicating that endogenous monoamines do not tonically activate ACh release. These results suggest that indeloxazine-induced facilitation of ACh release in rat frontal cortex is mediated by endogenous 5-HT and involves at least in part cortical 5-HT4 receptors.

  4. Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

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    Mario L Diaz

    2012-11-01

    Full Text Available Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene and DPH (1,6-diphenyl-1,3,5-hexatriene, we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviours, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity napp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. napp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-beta-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of

  5. Frontal cortex control dysfunction related to long-term suicide risk in recent-onset schizophrenia.

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    Minzenberg, Michael J; Lesh, Tyler A; Niendam, Tara A; Yoon, Jong H; Rhoades, Remy N; Carter, Cameron S

    2014-08-01

    Suicide is highly-prevalent and the most serious outcome in schizophrenia, yet the disturbances in neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in psychotic disorders, and various PFC changes are observed in post-mortem studies of completed suicide. We tested whether PFC activity during goal-representation (an important component of cognitive control) relates to long-term suicide risk in recent-onset schizophrenia. 35 patients with recent-onset of DSM-IV-TR-defined schizophrenia (SZ) were evaluated for long-term suicide risk (using the Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models associating control-related brain activation with suicide risk controlled for depression, psychosis and impulsivity. Within this group, past suicidal ideation was associated with lower activation with goal-representation demands in multiple PFC sectors. Among those with past suicidal ideation (n=18), reported suicidal behavior was associated with lower control-related activation in premotor cortex ipsilateral to the active primary motor cortex. This study provides unique evidence that suicide risk directly relates to PFC-based circuit dysfunction during goal-representation, in a major mental illness with significant suicide rates. Among those with suicidal ideation, the overt expression in suicidal behavior may stem from impairments in premotor cortex support of action-planning as an expression of control. Further work should address how PFC-based control function changes with risk over time, whether this brain-behavior relationship is specific to schizophrenia, and address its potential utility as a biomarker for interventions to mitigate suicide risk. Published by Elsevier B.V.

  6. Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex.

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    Zeba, Martina; Jovanov-Milosević, Natasa; Petanjek, Zdravko

    2008-01-01

    Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.

  7. Down syndrome: age-dependence of PiB binding in postmortem frontal cortex across the lifespan.

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    LeVine, Harry; Spielmann, H Peter; Matveev, Sergey; Cauvi, Francesca Macchiavello; Murphy, M Paul; Beckett, Tina L; McCarty, Katie; Lott, Ira T; Doran, Eric; Schmitt, Frederick; Head, Elizabeth

    2017-06-01

    Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro 3 H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (n = 25) and DS (n = 39). In DS, 3 H-PiB binding was significantly associated with age. After age 40 years in DS, 3 H-PiB binding rose dramatically along with increasing individual variability. 3 H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and cerebral amyloid angiopathy in DS brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. "Lipid raft aging" in the human frontal cortex during nonpathological aging: gender influences and potential implications in Alzheimer's disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Ferrer, Isidre; Marín, Raquel

    2018-03-10

    Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging. Main changes affect levels of plasmalogens, polyunsaturated fatty acids (especially docosahexaenoic acid and arachidonic acid), total polar lipids (mainly phosphatidylinositol, sphingomyelin, sulfatides, and cerebrosides), and total neutral lipids (particularly cholesterol and sterol esters). Besides, relevant relationships between main fatty acids and/or lipid classes were altered in an age-related manner. This "lipid raft aging" exhibits clear gender differences and appear to be more pronounced in women than in men, especially in older (postmenopausal) women. The outcomes led us to conclude that human cortical lipid rafts are modified by aging in a gender-dependent fashion. Given the central role of bilayer lipid matrix in lipid rafts functionality and neuronal signaling, we hypothesize that these findings might underlie the higher prevalence of cognitive decline evolving toward Alzheimer's disease in postmenopausal women. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

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    Tornero-Velez Rogelio

    2008-11-01

    Full Text Available Abstract Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg or permethrin (1 – 100 mg/kg followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM and isotonic regression (PIR methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1 was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25% in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of

  10. Effective Connectivity Hierarchically Links Temporoparietal and Frontal Areas of the Auditory Dorsal Stream with the Motor Cortex Lip Area during Speech Perception

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    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-01-01

    A left-hemispheric cortico-cortical network involving areas of the temporoparietal junction (Tpj) and the posterior inferior frontal gyrus (pIFG) is thought to support sensorimotor integration of speech perception into articulatory motor activation, but how this network links with the lip area of the primary motor cortex (M1) during speech…

  11. Differential changes in amygdala and frontal cortex Pde10a expression during acute and protracted withdrawal

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    Marian L Logrip

    2014-04-01

    Full Text Available Alcohol use disorders are persistent problems with high recidivism rates despite repeated efforts to quit drinking. Neuroadaptations that result from alcohol exposure and that persist during periods of abstinence represent putative molecular determinants of the propensity to relapse. Previously we demonstrated a positive association between phosphodiesterase 10A (PDE10A gene expression and elevations in relapse-like alcohol self-administration in rats with a history of stress exposure. Because alcohol withdrawal is characterized by heightened anxiety-like behavior, activation of stress-responsive brain regions and an elevated propensity to self-administer alcohol, we hypothesized that Pde10a expression also would be upregulated in reward- and stress-responsive brain regions during periods of acute (8-10 h and protracted (6 wk alcohol withdrawal. During acute withdrawal, elevated Pde10a mRNA expression was found in the medial and basolateral amygdala, as well as the infralimbic and anterior cingulate subdivisions of the medial prefrontal cortex, relative to alcohol-naïve controls. The basolateral amygdala was the only region with elevated Pde10a mRNA expression during both acute and protracted withdrawal. In contrast to the elevations, Pde10a mRNA levels tended to be reduced during protracted withdrawal in the dorsal striatum, prelimbic prefrontal cortex, and medial amygdala. Together these results implicate heightened PDE10A expression in the basolateral amygdala as a lasting neuroadaptation associated with alcohol dependence.

  12. β2-adrenoceptor stimulation restores frontal cortex plasticity and improves visuospatial performance in hidden-prenatally-malnourished young-adult rats.

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    Sáez-Briones, Patricio; Soto-Moyano, Rubén; Burgos, Héctor; Castillo, Amparo; Valladares, Luis; Morgan, Carlos; Pérez, Hernán; Barra, Rafael; Constandil, Luis; Laurido, Claudio; Hernández, Alejandro

    2015-03-01

    Moderate reduction in dietary protein composition of pregnant rats from 25% to 8% casein, calorically compensated by carbohydrates, has been described as a "hidden malnutrition" because it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to altered central noradrenergic systems, impaired cortical long-term potentiation (LTP) and worsened visuo-spatial memory performance. Given the increasing interest on the role played by β2-adrenoceptors (β2-ARs) on brain plasticity, the present study aimed to address the following in hidden-malnourished and eutrophic control rats: (i) the expression levels of β2-ARs in the frontal cortex determined by immunohistochemistry, and (ii) the effect of the β2 selective agonist clenbuterol on both LTP elicited in vivo in the prefrontal cortex and visuospatial performance measured in an eight-arm radial maze. Our results showed that, prenatally malnourished rats exhibited a significant reduction of neocortical β2-AR expression in adulthood. Concomitantly, they were unable to elicit and maintain prefrontal cortex LTP and exhibited lower visuospatial learning performance. Administration of clenbuterol (0.019, 0.038 and 0.075 mg/kg i.p.) enhanced LTP in malnourished and control animals and restored visuospatial learning performance in malnourished but not in normal rats, in a dose-dependent manner. The results suggest that decreased density of neocortical β2-ARs during postnatal life, subsequent to hidden prenatal malnutrition might affect some synaptic networks required to elicit neocortical LTP and form visuospatial memory, since those neuroplastic deficits were counteracted by β2-AR stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The functional role of individual-alpha based frontal asymmetry in stress responding

    NARCIS (Netherlands)

    Quaedflieg, C.W.E.M.; Meyer, T.; Smulders, F.T.Y.; Smeets, T.J.M.

    2015-01-01

    Asymmetry in frontal electrical activity has been suggested to index tendencies in affective responding and thus may be associated with hormonal stress responses. To assess the functional role of frontal asymmetry (FA) in stress, we measured FA at rest and following exposure to acute stress induced

  14. Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control

    Science.gov (United States)

    Schmidt, André; Walter, Marc; Gerber, Hana; Schmid, Otto; Smieskova, Renata; Bendfeldt, Kerstin; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Rubia, Katya; McGuire, Philip; Borgwardt, Stefan

    2013-01-01

    Impairments in inhibitory control and in stimulus-driven attention are hallmarks of drug addiction and are associated with decreased activation in the right inferior frontal gyrus (IFG). Although previous studies indicate that the response inhibition function is impaired in abstinent heroin dependents, and that this is mediated by reduced IFG activity, it remains completely unknown whether and how an acute dose of heroin modulates IFG activity during cognitive control in heroin-dependent patients. This study investigates the acute effects of heroin administration on IFG activity during response inhibition and stimulus-driven attention in heroin-dependent patients. Using a cross-over, double-blind, placebo-controlled design, saline and heroin were administered to 26 heroin-dependent patients from stable heroin-assisted treatment, while performing a Go/No–Go event-related functional magnetic resonance imaging task to assess right IFG activity during motor response inhibition, as well as during oddball-driven attention allocation. Relative to saline, heroin significantly reduced right IFG activity during both successful response inhibition and oddball-driven attention allocation, whereas it did not change right IFG activity during response inhibition after correction for the effect of attention allocation. These heroin-induced effects were not related to changes in drug craving, state anxiety, behavioral performance, or co-consumption of psychostimulant drugs. This study demonstrates that heroin administration acutely impairs stimulus-driven attention allocation, as indicated by reduced IFG activity in response to infrequently presented stimuli, and does not specifically modulate IFG activity during response inhibition. PMID:23673865

  15. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    Lisa Bellaïche

    2013-01-01

    Full Text Available Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN and error positivity (Pe originating from the medial prefrontal cortex (mPFC. Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS. Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

  16. Rapid eye movement (REM sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7 activity

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    Camarini R.

    1997-01-01

    Full Text Available Rapid eye movement (REM sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase controls acetylcholine (Ach availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12. Two additional groups, a home-cage control (N = 6 and a large platform control (N = 6, were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant, membrane-bound (100,000 g pellet and soluble (100,000 g supernatant Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1 in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8. There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2. Our results

  17. Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice.

    Science.gov (United States)

    Soumier, Amelie; Sibille, Etienne

    2014-08-01

    Reduced expression of somatostatin (SST) is reported across chronic brain conditions including major depression and normal aging. SST is a signaling neuropeptide and marker of gamma-amino butyric acid (GABA) neurons, which specifically inhibit pyramidal neuron dendrites. Studies in auditory cortex suggest that chronic reduction in dendritic inhibition induces compensatory homeostatic adaptations that oppose the effects of acute inhibition. Whether such mechanisms occur in frontal cortex (FC) and affect behavioral outcome is not known. Here, we used two complementary viral vector strategies to examine the effects of acute vs chronic inhibition of SST-positive neurons on behavioral emotionality in adult mice. SST-IRES-Cre mice were injected in FC (prelimbic/precingulate) with CRE-dependent adeno-associated viral (AAV) vector encoding the engineered Gi/o-coupled human muscarinic M4 designer receptor exclusively activated by a designer drug (DREADD-hM4Di) or a control reporter (AAV-DIO-mCherry) for acute or chronic cellular inhibition. A separate cohort was injected with CRE-dependent AAV vectors expressing diphtheria toxin (DTA) to selectively ablate FC SST neurons. Mice were assessed for anxiety- and depressive-like behaviors (defined as emotionality). Results indicate that acute inhibition of FC SST neurons increased behavioral emotionality, whereas chronic inhibition decreased behavioral emotionality. Furthermore, ablation of FC SST neurons also decreased behavioral emotionality under baseline condition and after chronic stress. Together, our results reveal opposite effects of acute and chronic inhibition of FC SST neurons on behavioral emotionality and suggest the recruitment of homeostatic plasticity mechanisms that have implications for understanding the neurobiology of chronic brain conditions affecting dendritic-targeting inhibitory neurons.

  18. The hAPP-YAC transgenic model has elevated UPS activity in the frontal cortex similar to Alzheimer's disease and Down's syndrome.

    Science.gov (United States)

    Seo, Hyemyung; Isacson, Ole

    2010-09-01

    The ubiquitin-proteasome system (UPS) is critical for handling the intra-cellular load of abnormal and misfolded proteins in several neurodegenerative diseases. First, to determine the effects of the over-expression of human amyloid precursor protein (hAPP) on UPS, we measured proteasome activities using fluorescent substrates in the frontal cortex of hAPP-yeast artificial chromosome (YAC) transgenic (tg) mice (R1.40, hemizygous; Lamb, Nat Genet, 9, 4; 1995). Chymotrypsin and PGPH-like activities of proteasome were increased in frontal cortex of hAPP-YAC tg mice. These proteasome activities (both chymotrypsin and PGPH-like) were further increased by cholinergic stimulation in littermate control mice, but not in hAPP-YAC tg mice. Nerve growth factor (NGF) levels were decreased by hAPP over-expression in the frontal cortex and hippocampus of hAPP-YAC tg mice, and further decreased by M1 agonist treatment in the hippocampus of littermate control and hAPP-YAC tg mice. Interestingly, the frontal cortex (BA9 area) of Alzheimer's disease (AD) patients (Stage 3, n=11) and Down's syndrome (DS) patients (n=9) showed similar up-regulation of the UPS activities to those seen in hAPP-YAC tg mice. M1 agonist stimulation increased the activities of α-secretase, which were down-regulated by hAPP over-expression in the frontal cortex of hAPP-YAC tg mice. These results demonstrate that (i) hAPP-YAC tg mice have an up-regulation in the frontal cortex of the UPS similar to AD and DS patients; (ii) muscarinic stimulation increase UPS activities, increase secreted APP (APPs) levels, and decrease amyloid beta 42/40 ratio only in littermate controls, but not in hAPP-YAC tg mice. Taken together, these results suggest that both the adaptive reactions in the proteostatic network and pathological changes in AD and DS need to be considered in the future potential therapeutics. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

  19. How Two Brains Make One Synchronized Mind in the Inferior Frontal Cortex: fNIRS-Based Hyperscanning During Cooperative Singing.

    Science.gov (United States)

    Osaka, Naoyuki; Minamoto, Takehiro; Yaoi, Ken; Azuma, Miyuki; Shimada, Yohko Minamoto; Osaka, Mariko

    2015-01-01

    One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing.

  20. A simultaneous modulation of reactive and proactive inhibition processes by anodal tDCS on the right inferior frontal cortex.

    Directory of Open Access Journals (Sweden)

    Toni Cunillera

    Full Text Available Proactive and reactive inhibitory processes are a fundamental part of executive functions, allowing a person to stop inappropriate responses when necessary and to adjust performance in in a long term in accordance to the goals of a task. In the current study, we manipulate, in a single task, both reactive and proactive inhibition mechanisms, and we investigate the within-subjects effect of increasing, by means of anodal transcranial direct current stimulation (tDCS, the involvement of the right inferior frontal cortex (rIFC. Our results show a simultaneous enhancement of these two cognitive mechanisms when modulating the neural activity of rIFC. Thus, the application of anodal tDCS increased reaction times on Go trials, indicating a possible increase in proactive inhibition. Concurrently, the stop-signal reaction time, as a covert index of the inhibitory process, was reduced, demonstrating an improvement in reactive inhibition. In summary, the current pattern of results validates the engagement of the rIFC in these two forms of inhibitory processes, proactive and reactive inhibition and it provides evidence that both processes can operate concurrently in the brain.

  1. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here

  2. Development of risk-taking: contributions from adolescent testosterone and the orbito-frontal cortex

    NARCIS (Netherlands)

    Peper, J.S.; Koolschijn, P.C.M.P.; Crone, E.A.

    2013-01-01

    The role of puberty in the development of risk taking remains poorly understood. Here, in a normative sample of 268 participants between 8 and 25 years old, we applied a psycho-endocrine neuroimaging approach to investigate the contribution of testosterone levels and OFC morphology to individual

  3. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  4. Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving.

    Directory of Open Access Journals (Sweden)

    Noriyuki Oka

    Full Text Available In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves, but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS.The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task. Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections.Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05, but cerebral oxygen exchange increased significantly more during left curves (p < 0.05 in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05 only in the right frontal eye field.Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

  5. Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex

    DEFF Research Database (Denmark)

    Severino, Maurizio; Pedersen, Anja F; Trajkovska, Viktorija

    2007-01-01

    Although loss of cholinergic neurons in the basal forebrain is considered a key initial feature in Alzheimer's disease (AD), changes in other transmitter systems, including serotonin and 5-HT(2A) receptors, are also associated with early AD. The aim of this study was to investigate whether...... elimination of the cholinergic neurons in the basal forebrain directly affects 5-HT(2A) receptor levels. For this purpose intraventricular injection of the selective immunotoxin 192 IgG-Saporin was given to rats in doses of either 2.5 or 5 microg. The rats were sacrificed after 1, 2, 4 and 20 weeks. 5-HT(2A......) protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT(2A) receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 Ig...

  6. Conflict-related dorsomedial frontal cortex activation during healthy food decisions is associated with increased cravings for high-fat foods.

    Science.gov (United States)

    Smith, Ryan; Alkozei, Anna; Killgore, William D S

    2017-04-27

    Previous studies suggest obesity is associated with altered function within the insula and dorsomedial frontal cortex (including dorsal anterior cingulate cortex; DMFC/dACC), reflecting abnormal reward processing and reduced sensitivity to feelings of satiety. Given the proposed roles of DMFC/dACC in monitoring response conflict and reward-based decision making, the present study examined DMFC/dACC activation, and functional connectivity between the DMFC/dACC and the anterior insula (AI), during food-related decision-making. Twenty participants recruited from the general population (10 Female) performed a decision task while undergoing functional magnetic resonance imaging. They were instructed to "choose the healthier option" when simultaneously shown pairs of images of different foods. Significant DMFC/dACC activation was observed during food-related decision-making, and activation levels also positively correlated with self-reported cravings for high-fat foods (r = 0.57, p = 0.009) and self-reported desire to eat the high-fat foods depicted in the images (r = 0.48, p = 0.032). Negative functional connectivity estimates between the right AI and DMFC/dACC were also associated with self-reported control over eating (r = -0.50, p = 0.025). These results suggest that (1) more intense cravings for unhealthy foods are associated with greater response conflict when deciding between healthy and unhealthy food options, and (2) lack of eating-related control may involve a reduced influence of insula-mediated bodily signals on decision-making. This task may offer a neuroimaging-based probe for identifying individuals vulnerable to eating-related disorders and should be replicated in clinical populations.

  7. TNFRSF11B computational development network construction and analysis between frontal cortex of HIV encephalitis (HIVE and HIVE-control patients

    Directory of Open Access Journals (Sweden)

    Jiang Ming H

    2010-09-01

    Full Text Available Abstract Background TNFRSF11B computational development network construction and analysis of frontal cortex of HIV encephalitis (HIVE is very useful to identify novel markers and potential targets for prognosis and therapy. Methods By integration of gene regulatory network infer (GRNInfer and the database for annotation, visualization and integrated discovery (DAVID we identified and constructed significant molecule TNFRSF11B development network from 12 frontal cortex of HIVE-control patients and 16 HIVE in the same GEO Dataset GDS1726. Results Our result verified TNFRSF11B developmental process only in the downstream of frontal cortex of HIVE-control patients (BST2, DGKG, GAS1, PDCD4, TGFBR3, VEZF1 inhibition, whereas in the upstream of frontal cortex of HIVE (DGKG, PDCD4 activation and downstream (CFDP1, DGKG, GAS1, PAX6 activation; BST2, PDCD4, TGFBR3, VEZF1 inhibition. Importantly, we datamined that TNFRSF11B development cluster of HIVE is involved in T-cell mediated immunity, cell projection organization and cell motion (only in HIVE terms without apoptosis, plasma membrane and kinase activity (only in HIVE-control patients terms, the condition is vital to inflammation, brain morphology and cognition impairment of HIVE. Our result demonstrated that common terms in both HIVE-control patients and HIVE include developmental process, signal transduction, negative regulation of cell proliferation, RNA-binding, zinc-finger, cell development, positive regulation of biological process and cell differentiation. Conclusions We deduced the stronger TNFRSF11B development network in HIVE consistent with our number computation. It would be necessary of the stronger TNFRSF11B development function to inflammation, brain morphology and cognition of HIVE.

  8. Development of risk taking: contributions from adolescent testosterone and the orbito-frontal cortex.

    Science.gov (United States)

    Peper, Jiska S; Koolschijn, P Cédric M P; Crone, Eveline A

    2013-12-01

    The role of puberty in the development of risk taking remains poorly understood. Here, in a normative sample of 268 participants between 8 and 25 years old, we applied a psycho-endocrine neuroimaging approach to investigate the contribution of testosterone levels and OFC morphology to individual differences in risk taking. Risk taking was measured with the balloon analogue risk-taking task. We found that, corrected for age, higher endogenous testosterone level was related to increased risk taking in boys (more explosions) and girls (more money earned). In addition, a smaller medial OFC volume in boys and larger OFC surface area in girls related to more risk taking. A mediation analysis indicated that OFC morphology partly mediates the association between testosterone level and risk taking, independent of age. Mediation was found in such a way that a smaller medial OFC in boys potentiates the association between testosterone and risk taking but suppresses the association in girls. This study provides insights into endocrinological and neural underpinnings of normative development of risk taking, by indicating that OFC morphology, at least partly, mediates the association between testosterone and risk-taking behavior.

  9. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats

    DEFF Research Database (Denmark)

    Mørk, A; Kreilgaard, Mads; Sánchez, C

    2003-01-01

    The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of an S(+)- and R(-)-enantiomer, escitalopram and R-citalopram, respectively. The present study compares the effects of escitalopram, R-citalopram and citalopram on extracellular levels of 5-HT in the frontal cortex...... of freely moving rats. In addition, co-injection of escitalopram and R-citalopram (ratios 1:2 and 1:4) were assessed. In some experiments escitalopram and R-citalopram were infused into the frontal cortex by reverse microdialysis. Finally, the extracellular level of escitalopram in the frontal cortex...... was studied after administration of escitalopram alone or in combination with R-citalopram. Escitalopram (1.0-3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than citalopram (2.0-8.0 mg/kg, s.c.). R-citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R...

  10. The enhanced information flow from visual cortex to frontal area facilitates SSVEP response: evidence from model-driven and data-driven causality analysis

    Science.gov (United States)

    Li, Fali; Tian, Yin; Zhang, Yangsong; Qiu, Kan; Tian, Chunyang; Jing, Wei; Liu, Tiejun; Xia, Yang; Guo, Daqing; Yao, Dezhong; Xu, Peng

    2015-10-01

    The neural mechanism of steady-state visual evoked potentials (SSVEP) is still not clearly understood. Especially, only certain frequency stimuli can evoke SSVEP. Our previous network study reveals that 8 Hz stimulus that can evoke strong SSVEP response shows the enhanced linkage strength between frontal and visual cortex. To further probe the directed information flow between the two cortex areas for various frequency stimuli, this paper develops a causality analysis based on the inversion of double columns model using particle swarm optimization (PSO) to characterize the directed information flow between visual and frontal cortices with the intracranial rat electroencephalograph (EEG). The estimated model parameters demonstrate that the 8 Hz stimulus shows the enhanced directional information flow from visual cortex to frontal lobe facilitates SSVEP response, which may account for the strong SSVEP response for 8 Hz stimulus. Furthermore, the similar finding is replicated by data-driven causality analysis. The inversion of neural mass model proposed in this study may be helpful to provide the new causality analysis to link the physiological model and the observed datasets in neuroscience and clinical researches.

  11. Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN) expression in frontal cortex and hippocampus of aged rat treated with high tryptophan diet.

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Castorina, Sergio; Imbesi, Rosa; Szychlinska, Marta Anna; Scuderi, Soraya; Loreto, Carla; Giunta, Salvatore

    2015-10-01

    Age-related cognitive decline is accompanied by an alteration in neurotransmitter synthesis and a dysregulation of neuroplasticity-related molecules such as serotonin (5-HT) and brain-derived neurotrophic factor (BDFN). It has been previously demonstrated that hyperserotonemia induced by l-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging. Since 5-HT is closely associated to BDNF, we aimed to investigate the effect of high TrP diet on 5-HT levels and BDNF expression in Frontal Cortex (FC) and Hippocampus (Hp) of aged rats. We found that the raising of systemic 5-HT levels by chronic diet (1 month) containing high TrP significantly prevents age-related decline of BDNF protein expression in both brain areas as indicated by ELISA and Western Blot analyses. Interestingly, immunohistochemical analyses confirmed that high TrP diet significantly elevates the number of 5-HT immunoreactive fibers in both brain areas tested and this correlated with BDNF increase in the FC and hippocampal regions CA1, CA2, CA3 and a strikingly down-regulation of neurotrophin levels in the dentate gyrus (DG) of aged rats. Altogether, these finding provide evidence that enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Motor cortex stimulation: role of computer modeling

    NARCIS (Netherlands)

    Manola, L.; Holsheimer, J.; Sakas, D.E.; Simpson, B.A

    Motor cortex stimulation (MCS) is a promising clinical technique used to treat chronic, otherwise intractable pain. However, the mechanisms by which the neural elements that are stimulated during MCS induce pain relief are not understood. Neither is it known which neural elements (fibers (parallel

  13. GABAA receptors, but not dopamine, serotonin or NMDA receptors, are increased in the frontal cortex from schizophrenic subjects

    International Nuclear Information System (INIS)

    Daen, B.; Hussain, T.; Scarr, E.; Tomaskovic, E.; Kitsoulis, S.; Pavey, G.; Hill, C.; Keks, N.; Opeskin, K.; Copolov, D.L.

    1998-01-01

    Full text: Having shown changed 5HT 2A receptor density in the frontal cortex (FC) from schizophrenic subjects (1) we now report on further studies of the molecular neuroanatomy of the FC in schizophrenia. We used in situ radioligand binding and autoradiography to measure the density of [ 3 H]8OH-DPAT (1 nM) binding (5HT 1A receptors) and [ 3 H]GR113808 (2.4nM) binding (5HT 4 receptors) in Brodmann's areas (BA) 8, 9 and 10 from 10 schizophrenic and 10 controls subjects. In addition, [ 3 H]muscimol (100 nM) binding (GABA A receptors), [ 3 H]TCP (20nM) binding (NMDA receptors), [ 3 H]SCH 23390 (3nM) binding (DA D 1 like receptors) and [ 3 H]YM-09151-2 (4nM) binding (DA D 2 -like receptors) was measured in BA 9 from 17 schizophrenic and 17 control subjects. Subjects were matched for age and sex and the post-mortem interval for tissue collection did not differ. There was a significant increase (18%) in the density of GABA A receptors in BA 9 from subjects with schizophrenia (p<0.05) with no change in NMDA, dopamine or serotonin receptors. These data support the hypothesis that there are selective changes in neurotransmitter receptors in the FC of subjects with schizophrenia. It is not yet clear if such changes contribute to the pathology of the illness. Copyright (1998) Australian Neuroscience Society

  14. Regulatory behavior and frontal activity: Considering the role of revised-BIS in relative right frontal asymmetry.

    Science.gov (United States)

    Gable, Philip A; Neal, Lauren B; Threadgill, A Hunter

    2018-01-01

    Essential to human behavior are three core personality systems: approach, avoidance, and a regulatory system governing the two motivational systems. Decades of research has linked approach motivation with greater relative left frontal-cortical asymmetry. Other research has linked avoidance motivation with greater relative right frontal-cortical asymmetry. However, past work linking withdrawal motivation with greater relative right frontal asymmetry has been mixed. The current article reviews evidence suggesting that activation of the regulatory system (revised Behavioral Inhibition System [r-BIS]) may be more strongly related to greater relative right frontal asymmetry than withdrawal motivation. Specifically, research suggests that greater activation of the r-BIS is associated with greater relative right frontal activity, and reduced r-BIS activation is associated with reduced right frontal activity (greater relative left frontal activity). We review evidence examining trait and state frontal activity using EEG, source localization, lesion studies, neuronal stimulation, and fMRI supporting the idea that r-BIS may be the core personality system related to greater relative right frontal activity. In addition, the current review seeks to disentangle avoidance motivation and r-BIS as substrates of relative right frontal asymmetry. © 2017 Society for Psychophysiological Research.

  15. Increased gene expression of selected vesicular and glial glutamate transporters in the frontal cortex in rats exposed to voluntary wheel running.

    Science.gov (United States)

    Graban, J; Hlavacova, N; Jezova, D

    2017-10-01

    Though positive effects of exercise on mood and well being are well recognised, the central regulatory mechanisms are still not fully understood. The present study was aimed to testing the hypothesis that voluntary wheel running activates the gene expression of glutamate transporters in the brain cortex of rats. The animals were assigned to the control and voluntary wheel running groups. Voluntary wheel running rats had free access to a stainless steel activity wheel for 3 weeks. The daily running distance gradually increased to 6.21 ± 1.05 km by day 21. Vesicular glutamate transporter 3 (VGLUT3) mRNA levels in the frontal cortex were significantly elevated in the group of running animals compared to the values in sedentary controls, while the expression of other vesicular transporters were unchanged. The concentrations of mRNA coding for glial glutamate transporter 1 (GLT-1), but not glutamate aspartate transporter (GLAST) were increased by running. Voluntary wheel running resulted in an elevation of plasma corticosterone and increased expression of brain derived neurotrophic factor (BDNF) in the frontal cortex. In conclusion, chronic voluntary wheel running results in increased gene expression of VGLUT3 and GLT-1 in the brain cortex without changes in other glutamate transporter subtypes.

  16. Maudsley Bipolar Disorder Project: insights sobre o papel do córtex pré-frontal em pacientes com transtorno de humor bipolar tipo I Proyecto Maudsley para Trastorno Bipolar: insights sobre el rol del córtex prefrontal en casos de disturbio bipolar I The Maudsley Bipolar Disorder Project: insights into the role of the prefrontal cortex in bipolar disorder I

    Directory of Open Access Journals (Sweden)

    Morgan Haldane

    2005-12-01

    Full Text Available OBJETIVO: O projeto Maudsley Bipolar Disorder foi criado para investigar características cognitivas e estruturais/funcionais do cérebro em pacientes com Transtorno de Humor Bipolar Tipo I (THB-I. MÉTODOS: Quarenta e três pacientes com THB-I foram selecionados em uma unidade de atendimento secundário, em um momento de remissão da doença, para participarem do estudo. Os pacientes foram pareados a controles sadios de acordo com idade, sexo, raça e nível de escolaridade. Cada participante foi submetido a uma extensa revisão clínica, com avaliação cognitiva e exame de ressonância magnética (RM para a obtenção de dados estruturais e funcionais do cérebro. RESULTADOS: Quando comparados aos controles, os pacientes demonstraram um sutil e difuso comprometimento com redução mais marcante no nível das funções executivas. Os pacientes também apresentaram decrementos volumétricos no córtex pré-frontal ventral (CPFV bilateralmente e córtex pré-frontal dorsal (CPFD esquerdo. O volume da amígdala estava bilateralmente aumentado. A ressonância magnética funcional (RMf mostrou anormalidades sutis no CPFD, com marcados decrementos de atividade tanto no CPFD como no CPFV durante tarefas que dependiam da interação funcional dessas regiões. CONCLUSÕES: Os resultados sugerem que ocorrem traços de déficits em funções executivas em pacientes com THB-I, assim como alteração de estrutura e funcionamento do córtex pré-frontal.OBJETIVO: El proyecto Maudsley para Trastorno Bipolar fue creado para investigar características cognitivas y estructurales/funcionales del cerebro en pacientes con Trastorno Bipolar I (TBI. MÉTODOS: Cuarenta y tres pacientes con TBI han sido elegidos en una unidad de atención secundaria para participar del estudio, en un momento de remisión de la enfermedad. Los pacientes han sido pareados a controles sanos conforme a edad, sexo, raza y nivel de escolaridad. Cada participante ha sido sometido a una

  17. Temporal Evolution of Target Representation, Movement Direction Planning, and Reach Execution in Occipital-Parietal-Frontal Cortex: An fMRI Study.

    Science.gov (United States)

    Cappadocia, David C; Monaco, Simona; Chen, Ying; Blohm, Gunnar; Crawford, J Douglas

    2017-11-01

    The cortical mechanisms for reach have been studied extensively, but directionally selective mechanisms for visuospatial target memory, movement planning, and movement execution have not been clearly differentiated in the human. We used an event-related fMRI design with a visuospatial memory delay, followed by a pro-/anti-reach instruction, a planning delay, and finally a "go" instruction for movement. This sequence yielded temporally separable preparatory responses that expanded from modest parieto-frontal activation for visual target memory to broad occipital-parietal-frontal activation during planning and execution. Using the pro/anti instruction to differentiate visual and motor directional selectivity during planning, we found that one occipital area showed contralateral "visual" selectivity, whereas a broad constellation of left hemisphere occipital, parietal, and frontal areas showed contralateral "movement" selectivity. Temporal analysis of these areas through the entire memory-planning sequence revealed early visual selectivity in most areas, followed by movement selectivity in most areas, with all areas showing a stereotypical visuo-movement transition. Cross-correlation of these spatial parameters through time revealed separate spatiotemporally correlated modules for visual input, motor output, and visuo-movement transformations that spanned occipital, parietal, and frontal cortex. These results demonstrate a highly distributed occipital-parietal-frontal reach network involved in the transformation of retrospective sensory information into prospective movement plans. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Beyond reversal: a critical role for human orbitofrontal cortex in flexible learning from probabilistic feedback.

    Science.gov (United States)

    Tsuchida, Ami; Doll, Bradley B; Fellows, Lesley K

    2010-12-15

    Damage to the orbitofrontal cortex (OFC) has been linked to impaired reinforcement processing and maladaptive behavior in changing environments across species. Flexible stimulus-outcome learning, canonically captured by reversal learning tasks, has been shown to rely critically on OFC in rats, monkeys, and humans. However, the precise role of OFC in this learning remains unclear. Furthermore, whether other frontal regions also contribute has not been definitively established, particularly in humans. In the present study, a reversal learning task with probabilistic feedback was administered to 39 patients with focal lesions affecting various sectors of the frontal lobes and to 51 healthy, demographically matched control subjects. Standard groupwise comparisons were supplemented with voxel-based lesion-symptom mapping to identify regions within the frontal lobes critical for task performance. Learning in this dynamic stimulus-reinforcement environment was considered both in terms of overall performance and at the trial-by-trial level. In this challenging, probabilistic context, OFC damage disrupted both initial and reversal learning. Trial-by-trial performance patterns suggest that OFC plays a critical role in interpreting feedback from a particular trial within the broader context of the outcome history across trials rather than in simply suppressing preexisting stimulus-outcome associations. The findings show that OFC, and not other prefrontal regions, plays a necessary role in flexible stimulus-reinforcement learning in humans.

  19. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

    Directory of Open Access Journals (Sweden)

    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  20. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

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    Minchenko Dimitri

    2010-04-01

    Full Text Available Abstract Background The Rett Syndrome (RTT brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1 or are involved in synaptic vesicle cycling (dynamin 1. RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited.

  1. Transcranial Direct Current Stimulation Over the Right Frontal Inferior Cortex Decreases Neural Activity Needed to Achieve Inhibition: A Double-Blind ERP Study in a Male Population.

    Science.gov (United States)

    Campanella, Salvatore; Schroder, Elisa; Monnart, Aurore; Vanderhasselt, Marie-Anne; Duprat, Romain; Rabijns, Mark; Kornreich, Charles; Verbanck, Paul; Baeken, Chris

    2017-05-01

    Inhibitory control refers to the ability to inhibit an action once it has been initiated. Impaired inhibitory control plays a key role in triggering relapse in some pathological states, such as addictions. Therefore, a major challenge of current research is to establish new methods to strengthen inhibitory control in these "high-risk" populations. In this attempt, the right inferior frontal cortex (rIFC), a neural correlate crucial for inhibitory control, was modulated using transcranial direct current stimulation (tDCS). Healthy participants (n = 31) were presented with a "Go/No-go" task, a well-known paradigm to measure inhibitory control. During this task, an event-related potential (ERP) recording (T1; 32 channels) was performed. One subgroup (n = 15) was randomly assigned to a condition with tDCS (anodal electrode was placed on the rIFC and the cathodal on the neck); and the other group (n = 16) to a condition with sham (placebo) tDCS. After one 20- minute neuromodulation session, all participants were confronted again with the same ERP Go/No-go task (T2). To ensure that potential tDCS effects were specific to inhibition, ERPs to a face-detection task were also recorded at T1 and T2 in both subgroups. The rate of commission errors on the Go/No-go task was similar between T1 and T2 in both neuromodulation groups. However, the amplitude of the P3d component, indexing the inhibition function per se, was reduced at T2 as compared with T1. This effect was specific for participants in the tDCS (and not sham) condition for correctly inhibited trials. No difference in the P3 component was observable between both subgroups at T1 and T2 for the face detection task. Overall, the present data indicate that boosting the rIFC specifically enhances inhibitory skills by decreasing the neural activity needed to correctly inhibit a response.

  2. Depressive-like history alters persistent pain behavior in rats: Opposite contribution of frontal cortex and amygdala implied.

    Science.gov (United States)

    Qi, Wei-Jing; Wang, Wei; Wang, Ning; Wang, Jin-Yan; Luo, Fei

    2013-08-01

    Numerous studies have shown that pain perception is strongly influenced by depression. However, very few studies have examined whether pain perception is altered in the remission period of depression, and what role the fronto-limbic circuits may play in the behavioral changes associated with remission. Using an unpredictable chronic mild stress (UCMS) animal model of depression, the present study investigated pain-related behaviors in rats with prior exposure to a UCMS stimulus. The γ-aminobutyric acid (GABA) A receptor agonist muscimol was microinjected bilaterally into the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) to examine the modulation of pain by these brain regions in the recovery state. Rats with a depression-like history displayed increased ongoing pain behavior in the formalin test, although their thermal pain thresholds were unchanged. Intra-BLA muscimol during the recovery phase dramatically decreased formalin-induced pain behavior and also significantly increased rats' sucrose preference. By contrast, in the mPFC, muscimol produced the opposite effect, suggesting different, perhaps opposing, roles of the BLA and mPFC in mediating the influence of prior UCMS exposure on pain perception. Taken together, these results demonstrated that a depressive experience may cause long-term alterations in limbic circuit excitability and thus lead to long-lasting changes in pain perception.

  3. The Role of Frontal Executive Functions in Hypnosis and Hypnotic Suggestibility

    OpenAIRE

    Parris, Benjamin

    2016-01-01

    There is both theoretical and empirical evidence supporting a role for frontal executive functions (FEFs) in hypnosis and hypnotic suggestibility. However, the precise nature of this involvement is debated. While there is clear evidence that FEFs are impaired under hypnosis, the cause of this decreased function is unclear. Theories make differing predictions as to the role of FEFs in hypnotic suggestibility, with some arguing that decreased baseline (normal function outside of the hypnotic co...

  4. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats

    DEFF Research Database (Denmark)

    Mørk, A; Kreilgaard, Mads; Sánchez, C

    2003-01-01

    The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of an S(+)- and R(-)-enantiomer, escitalopram and R-citalopram, respectively. The present study compares the effects of escitalopram, R-citalopram and citalopram on extracellular levels of 5-HT in the frontal cortex...... was studied after administration of escitalopram alone or in combination with R-citalopram. Escitalopram (1.0-3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than citalopram (2.0-8.0 mg/kg, s.c.). R-citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R......-citalopram counteracted the escitalopram-induced increase in extracellular 5-HT levels. Local infusion of the two enantiomers into the frontal cortex produced a similar inhibitory response. R-citalopram did not influence the extracellular levels of escitalopram and therefore does not exert its effect via...

  5. The multisensory roles for auditory cortex in primate vocal communication.

    Science.gov (United States)

    Ghazanfar, Asif A

    2009-12-01

    Primate vocal communication is a fundamentally multisensory behavior and this will be reflected in the different roles brain regions play in mediating it. Auditory cortex is illustrative, being influenced, I will argue, by the visual, somatosensory, proprioceptive and motor modalities during vocal communication. It is my intention that the data reviewed here suggest that investigating auditory cortex through the lens of a specific behavior may lead to a much clearer picture of its functions and dynamic organization. One possibility is that, beyond its tonotopic and cytoarchitectural organization, the auditory cortex may be organized according to ethologically-relevant actions. Such action-specific representations would be overlayed on top of traditional mapping schemes and would help mediate motor and multisensory processes related to a particular type of behavior.

  6. Disrupted Reinforcement Signaling in Orbital Frontal Cortex and Caudate in Youths with Conduct Disorder/Oppositional Defiant Disorder and High Psychopathic Traits

    Science.gov (United States)

    Finger, Elizabeth C.; Marsh, Abigail A.; Blair, Karina S.; Reid, Marguerite. E.; Sims, Courtney; Ng, Pamela; Pine, Daniel S.; Blair, R. James. R.

    2010-01-01

    OBJECTIVE Dysfunction in amygdala and orbital frontal cortex functioning has been reported in youths and adults with psychopathic traits. However, the specific nature of the computational irregularities within these brain structures remains poorly understood. The current study used the passive avoidance task to examine responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. METHOD 30 youths (N=15 with conduct disorder or oppositional defiant disorder plus high psychopathic traits and N=15 comparison subjects) completed a 3.0 T fMRI scan while performing a passive avoidance learning task. RESULTS Relative to comparison youth, youths with conduct disorder or oppositional defiant disorder plus psychopathic traits showed reduced orbitofrontal cortex responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as reduced caudate response to early stimulus-reinforcement exposure. Contrary to other predictions, however, there were no group differences in amygdala responsiveness specifically to these two task parameters. However, amygdala responsiveness throughout the task was reduced in the youths with conduct disorder or oppositional defiant disorder plus psychopathic traits. CONCLUSIONS This study demonstrates that youths with conduct disorder or oppositional defiant disorder plus psychopathic traits are marked by a compromised sensitivity to early reinforcement information in both orbitofrontal cortex and caudate and to reward outcome information within orbitofrontal cortex. They further suggest that the integrated functioning of the amygdala, caudate and orbitofrontal cortex may be disrupted in individuals with this disorder. PMID:21078707

  7. 5-HT2A Receptor Binding in the Frontal Cortex of Parkinson's Disease Patients and Alpha-Synuclein Overexpressing Mice: A Postmortem Study.

    Science.gov (United States)

    Rasmussen, Nadja Bredo; Olesen, Mikkel Vestergaard; Brudek, Tomasz; Plenge, Per; Klein, Anders Bue; Westin, Jenny E; Fog, Karina; Wörtwein, Gitta; Aznar, Susana

    2016-01-01

    The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer's disease and related to the disease pathology. Even though Parkinson's disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson's brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations. Binding density for the 5-HT2A-specific radioligand [(3)H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased 5-HT2A receptor binding in PD brains. In a separate study, we looked for changes in 5-HT2A receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific 5-HT2A receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower 5-HT2A binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression.

  8. Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects.

    Science.gov (United States)

    Zhubi, Adrian; Chen, Ying; Guidotti, Alessandro; Grayson, Dennis R

    2017-11-01

    Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain. Our goal is to better understand the molecular basis for the down-regulation of genes expressed in GABAergic neurons in ASD brains. We measured mRNA levels corresponding to selected GABAergic genes using qRT-PCR in RNA isolated from both ASD and CON groups. We determined the extent of binding of MECP2 and DNMT1 repressor proteins by chromatin immunoprecipitation (ChIP) assays. The amount of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) present in the promoters of the target genes was quantified by methyl DNA immunoprecipitation (MeDIP) and hydroxyl MeDIP (hMeDIP). We detected significant reductions in the mRNAs associated with RELN and GAD1 and significant increases in mRNAs encoding the Ten-eleven Translocation (TET) enzymes 1, 2, and 3. We also detected increased MECP2 and DNMT1 binding to the corresponding promoter regions of GAD1, RELN, and GAD2. Interestingly, there were decreased amounts of 5mC at both promoters and little change in 5hmC content in these same DNA fragments. Our data demonstrate that RELN, GAD1, and several other genes selectively expressed in GABAergic neurons, are down-regulated in post-mortem ASD FC. In addition, we observed increased DNMT1 and MECP2 binding at the corresponding promoters of these genes. The finding of increased MECP2 binding to the RELN, GAD1 and GAD2 promoters, with reduced amounts of 5mC and unchanged

  9. Norepinephrine in the Medial Pre-frontal Cortex Supports Accumbens Shell Responses to a Novel Palatable Food in Food-Restricted Mice Only

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    Emanuele Claudio Latagliata

    2018-01-01

    Full Text Available Previous findings from this laboratory demonstrate: (1 that different classes of addictive drugs require intact norepinephrine (NE transmission in the medial pre Frontal Cortex (mpFC to promote conditioned place preference and to increase dopamine (DA tone in the nucleus accumbens shell (NAc Shell; (2 that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3 that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances.

  10. Norepinephrine in the Medial Pre-frontal Cortex Supports Accumbens Shell Responses to a Novel Palatable Food in Food-Restricted Mice Only.

    Science.gov (United States)

    Latagliata, Emanuele Claudio; Puglisi-Allegra, Stefano; Ventura, Rossella; Cabib, Simona

    2018-01-01

    Previous findings from this laboratory demonstrate: (1) that different classes of addictive drugs require intact norepinephrine (NE) transmission in the medial pre Frontal Cortex (mpFC) to promote conditioned place preference and to increase dopamine (DA) tone in the nucleus accumbens shell (NAc Shell); (2) that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3) that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food-restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances.

  11. The role of frontal-subcortical circuits in the development of obsessive-compulsive disorders

    OpenAIRE

    M. A. Kutlubaev

    2016-01-01

    The paper presents a concise review of investigations into the role of impaired frontal-subcortical circuits in the development of obsessive-compulsive disorder (OCD). It gives data on the frequency of neurosis-like symptoms of the OCD spectrum in neurological diseases.The development of OCD is associated with an imbalance between the activity of the direct (activating) and indirect (inhibitory) pathways of the cortico-striatal-thalamo-cortical feedback loop. These data are confirmed by the r...

  12. Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes.

    Science.gov (United States)

    Sárvári, Miklós; Hrabovszky, Erik; Kalló, Imre; Solymosi, Norbert; Likó, István; Berchtold, Nicole; Cotman, Carl; Liposits, Zsolt

    2012-12-03

    The intricate interactions between the immune, endocrine and central nervous systems shape the innate immune response of the brain. We have previously shown that estradiol suppresses expression of immune genes in the frontal cortex of middle-aged ovariectomized rats, but not in young ones reflecting elevated expression of these genes in middle-aged, ovarian hormone deficient animals. Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia. We selected twenty-three genes encoding phagocytic and recognition receptors expressed primarily in microglia, and eleven proinflammatory genes and followed their expression in the rat frontal cortex by real-time PCR. We used young, middle-aged and middle-aged ovariectomized rats to reveal age- and ovariectomy-related alterations. We analyzed the expression of the same set of genes in the postcentral and superior frontal gyrus of pre- and postmenopausal women using raw microarray data from our previous study. Ovariectomy caused up-regulation of four classic microglia reactivity marker genes including Cd11b, Cd18, Cd45 and Cd86. The change was reversible since estradiol attenuated transcriptional activation of the four marker genes. Expression of genes encoding phagocytic and toll-like receptors such as Cd11b, Cd18, C3, Cd32, Msr2 and Tlr4 increased, whereas scavenger receptor Cd36 decreased following ovariectomy. Ovarian hormone deprivation altered the expression of major components of estrogen and neuronal inhibitory signaling which are involved in the control of microglia reactivity. Strikingly similar changes took place in the postcentral and superior frontal gyrus of postmenopausal women. Based on the overlapping results of rat and human studies we propose that the microglia phenotype shifts from the resting toward the reactive state which can be characterized by up-regulation of CD11b, CD14, CD18, CD45

  13. Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes

    Directory of Open Access Journals (Sweden)

    Sárvári Miklós

    2012-12-01

    Full Text Available Abstract Background The intricate interactions between the immune, endocrine and central nervous systems shape the innate immune response of the brain. We have previously shown that estradiol suppresses expression of immune genes in the frontal cortex of middle-aged ovariectomized rats, but not in young ones reflecting elevated expression of these genes in middle-aged, ovarian hormone deficient animals. Here, we explored the impact of menopause on the microglia phenotype capitalizing on the differential expression of macrophage-associated genes in quiescent and activated microglia. Methods We selected twenty-three genes encoding phagocytic and recognition receptors expressed primarily in microglia, and eleven proinflammatory genes and followed their expression in the rat frontal cortex by real-time PCR. We used young, middle-aged and middle-aged ovariectomized rats to reveal age- and ovariectomy-related alterations. We analyzed the expression of the same set of genes in the postcentral and superior frontal gyrus of pre- and postmenopausal women using raw microarray data from our previous study. Results Ovariectomy caused up-regulation of four classic microglia reactivity marker genes including Cd11b, Cd18, Cd45 and Cd86. The change was reversible since estradiol attenuated transcriptional activation of the four marker genes. Expression of genes encoding phagocytic and toll-like receptors such as Cd11b, Cd18, C3, Cd32, Msr2 and Tlr4 increased, whereas scavenger receptor Cd36 decreased following ovariectomy. Ovarian hormone deprivation altered the expression of major components of estrogen and neuronal inhibitory signaling which are involved in the control of microglia reactivity. Strikingly similar changes took place in the postcentral and superior frontal gyrus of postmenopausal women. Conclusions Based on the overlapping results of rat and human studies we propose that the microglia phenotype shifts from the resting toward the reactive state

  14. Retention and relearning of spatial delayed alternation in rats after combined or sequential lesions of the prefrontal and parietal cortex

    DEFF Research Database (Denmark)

    Wörtwein, Gitta; Mogensen, Jesper; Divac, Ivan

    1993-01-01

    Neurobiologi, præfrontal cortex, delayed alternation, rotte, parietal cortex, funktionel genopretning......Neurobiologi, præfrontal cortex, delayed alternation, rotte, parietal cortex, funktionel genopretning...

  15. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    Many psychiatric disorders are characterized by cognitive and emotional alterations that are related to abnormal function of the frontal cortex (FC). FC is involved in working memory and decision making and is activated following exposure to a novel environment. The serotonin 2A receptor (5-HT(2A......)R) is highly expressed in the FC where its activation induces hallucinations, while blockade of 5-HT(2A)Rs contributes to the therapeutic effects of atypical antipsychotic drugs. The purpose of the present study was to investigate the involvement of 5-HT(2A)R in FC activation following exposure to a novel...... environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (∼160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

  16. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    Many psychiatric disorders are characterized by cognitive and emotional alterations that are related to abnormal function of the frontal cortex (FC). FC is involved in working memory and decision making and is activated following exposure to a novel environment. The serotonin 2A receptor (5-HT(2A......)R) is highly expressed in the FC where its activation induces hallucinations, while blockade of 5-HT(2A)Rs contributes to the therapeutic effects of atypical antipsychotic drugs. The purpose of the present study was to investigate the involvement of 5-HT(2A)R in FC activation following exposure to a novel...... environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (~160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

  17. The Role of the Frontal Lobe in Complex Walking Among Patients With Parkinson's Disease and Healthy Older Adults: An fNIRS Study.

    Science.gov (United States)

    Maidan, Inbal; Nieuwhof, Freek; Bernad-Elazari, Hagar; Reelick, Miriam F; Bloem, Bas R; Giladi, Nir; Deutsch, Judith E; Hausdorff, Jeffery M; Claassen, Jurgen A H; Mirelman, Anat

    2016-11-01

    Gait is influenced by higher order cognitive and cortical control mechanisms. Functional near infrared spectroscopy (fNIRS) has been used to examine frontal activation during walking in healthy older adults, reporting increased oxygenated hemoglobin (HbO2) levels during dual task walking (DT), compared with usual walking. To investigate the role of the frontal lobe during DT and obstacle negotiation, in healthy older adults and patients with Parkinson's disease (PD). Thirty-eight healthy older adults (mean age 70.4 ± 0.9 years) and 68 patients with PD (mean age 71.7 ± 1.1 years,) performed 3 walking tasks: (a) usual walking, (b) DT walking, and (c) obstacles negotiation, with fNIRS and accelerometers. Linear-mix models were used to detect changes between groups and within tasks. Patients with PD had higher activation during usual walking (P frontal activation during walking was observed between groups. The higher activation during usual walking in patients with PD suggests that the prefrontal cortex plays an important role already during simple walking. However, higher activation relative to baseline during obstacle negotiation and not during DT in the patients with PD demonstrates that prefrontal activation depends on the nature of the task. These findings may have important implications for rehabilitation of gait in patients with PD. © The Author(s) 2016.

  18. fMRI identifies the right inferior frontal cortex as the brain region where time interval processing is altered by negative emotional arousal.

    Science.gov (United States)

    Pfeuty, Micha; Dilharreguy, Bixente; Gerlier, Loïc; Allard, Michèle

    2015-03-01

    The reason why human beings are inclined to overestimate the duration of highly arousing negative events remains enigmatic. The issue about what neurocognitive mechanisms and neural structures support the connection between time perception and emotion was addressed here by an event-related neuroimaging study involving a localizer task, followed by the main experiment. The localizer task, in which participants had to categorize either the duration or the average color of visual stimuli aimed at identifying the neural structures constitutive of a duration-specific network. The aim of the main experiment, in which participants had to categorize the presentation time of either neutral or emotionally negative visual stimuli, was to unmask which parts of the previously identified duration-specific network are sensitive to emotionally negative arousal. The duration-specific network that we uncovered from the localizer task comprised the cerebellum bilaterally as well as the orbitofrontal, the anterior cingulate, the anterior insular, and the inferior frontal cortices in the right hemisphere. Strikingly, the imaging data from the main experiment underscored that the right inferior frontal cortex (IFC) was the only region within the duration-specific network whose activity was increased in the face of emotionally negative pictures compared to neutral ones. Remarkably too, the extent of neural activation induced by emotionally negative pictures (compared to neutral ones) in this region correlated with a behavioral index reflecting the extent to which emotionally negative pictures were overestimated compared to neutral ones. The results are discussed in relation to recent models and studies suggesting that the right anterior insular cortex/IFC is of central importance in time perception. © 2014 Wiley Periodicals, Inc.

  19. Identification and characterization of muscarinic receptors potentiating the stimulation of adenylyl cyclase activity by corticotropin-releasing hormone in membranes of rat frontal cortex.

    Science.gov (United States)

    Onali, P; Olianas, M C

    1998-08-01

    In membranes of the rat frontal cortex, acetylcholine (ACh) and other cholinergic agonists were found to potentiate the stimulation of adenylyl cyclase activity elicited by corticotropin-releasing hormone (CRH). Oxotremorine-M, carbachol and methacholine were as effective as ACh, whereas oxotremorine and arecoline were much less effective. The facilitating effect of Ach was potently blocked by the M1 antagonists R-trihexyphenidyl, telenzepine and pirenzepine and by the M3 antagonists hexahydro-sila-difenidol and p-fluorohexahydro-sila-difenidol, whereas the M2 and M4 antagonists himbacine, methoctramine, AF-DX 116 and AQ-RA 741 were less potent. The mamba venom toxin MT-1, which binds with high affinity to M1 receptors, was also a potent blocker. The pharmacological profile of the muscarinic potentiation of CRH receptor activity was markedly different from that displayed by the muscarinic inhibition of forskolin-stimulated adenylyl cyclase, which could be detected in the same membrane preparations. Moreover, the intracerebral injection of pertussis toxin impaired the muscarinic inhibition of cyclic AMP formation and reduced the Ach stimulation of [35S]GTPgammaS binding to membrane G proteins but failed to affect the facilitating effect on CRH receptor activity. The latter response was also insensitive to the phospholipase C inhibitor U-73122, the protein kinase inhibitor staurosporine and to the inhibitors of arachidonic acid metabolism indomethacin and nordihydroguaiaretic acid. These data demonstrate that in the rat frontal cortex, muscarinic receptors of the M1 subtype potentiate CRH transmission by interacting with pertussis toxin-insensitive G proteins.

  20. Contrasting roles for lateral and ventromedial prefrontal cortex in transient and dispositional affective experience.

    Science.gov (United States)

    Gillihan, Seth J; Xia, Chenjie; Padon, Alisa A; Heberlein, Andrea S; Farah, Martha J; Fellows, Lesley K

    2011-01-01

    Prefrontal cortex (PFC) has been implicated in the experience and regulation of emotional states. Emotional experience is a complex construct, encompassing a range of more specific processes. This exploratory study aimed to delineate which (if any) aspects of emotional experience rely critically on either the ventromedial frontal (VMF) or lateral frontal (LF) lobes. The affective experience of individuals with damage to these regions was surveyed in detail using several measures and compared with that of control participants. Dependent measures included subjective and observer ratings of both dispositional affect and transient responses to laboratory mood inductions. VMF damage was associated with greater negative dispositional affect relative to controls and to individuals with LF damage; however, transient responses to emotional stimuli were largely normal. In contrast, LF damage was associated with an exaggerated subjective reactivity to sad emotional stimuli relative to control participants, but normal dispositional affect. Interestingly, neither form of PFC damage affected spontaneous emotion recovery following the mood inductions. These findings suggest a role for VMF in modulating dispositional negative affect; in contrast, LF areas appear to be critical in regulating transient emotional responses while emotional stimuli are present. This study also illustrates the dissociability of different aspects of emotional experience in patients with focal brain injury.

  1. Predicting treatment response in Schizophrenia: the role of stratal and frontal dopamine D2/D3 receptor binding potential

    DEFF Research Database (Denmark)

    Wulff, Sanne; Nørbak-Emig, Henrik; Nielsen, Mette Ødegaard

    2014-01-01

    relationship between frontal and striatal dopamine activity. Data also emphasize that there might be gender differences. The data analysis is ongoing. (1) Glenthøj BY, Mackeprang T et al. Frontal dopamine D2/3 receptor binding in drug-naïve first-episode schizophrenic patients correlates with positive...... cortex in antipsychotic-naïve first-episode male schizophrenia patients(1). Preclinical studies suggest an inverse relationship between frontal and striatal dopamine activity. This activity can indirectly be expressed by the BP of dopamine receptors using Single Photon Emission Computed Tomography (SPECT......-up. There was a negative correlation between striatal BP and improvement of the PANSS total score (Rho=-0,553 P=0.009). Furthermore we found a negative correlation between striatal BP and improvement of positive symptoms among the male patients only (P=0.020). The same relationship was found at trend level for the entire...

  2. Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

    Directory of Open Access Journals (Sweden)

    Leon French

    2017-05-01

    Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

  3. Frontal cortex and hippocampus neurotransmitter receptor complex level parallels spatial memory performance in the radial arm maze.

    Science.gov (United States)

    Shanmugasundaram, Bharanidharan; Sase, Ajinkya; Miklosi, András G; Sialana, Fernando J; Subramaniyan, Saraswathi; Aher, Yogesh D; Gröger, Marion; Höger, Harald; Bennett, Keiryn L; Lubec, Gert

    2015-08-01

    Several neurotransmitter receptors have been proposed to be involved in memory formation. However, information on receptor complexes (RCs) in the radial arm maze (RAM) is missing. It was therefore the aim of this study to determine major neurotransmitter RCs levels that are modulated by RAM training because receptors are known to work in homo-or heteromeric assemblies. Immediate early gene Arc expression was determined by immunohistochemistry to show if prefrontal cortices (PFC) and hippocampi were activated following RAM training as these regions are known to be mainly implicated in spatial memory. Twelve rats per group, trained and untrained in the twelve arm RAM were used, frontal cortices and hippocampi were taken, RCs in membrane protein were quantified by blue-native PAGE immunoblotting. RCs components were characterised by co-immunoprecipitation followed by mass spectrometrical analysis and by the use of the proximity ligation assay. Arc expression was significantly higher in PFC of trained as compared to untrained rats whereas it was comparable in hippocampi. Frontal cortical levels of RCs containing AMPA receptors GluA1, GluA2, NMDA receptors GluN1 and GluN2A, dopamine receptor D1, acetylcholine nicotinic receptor alpha 7 (nAChR-α7) and hippocampal levels of RCs containing D1, GluN1, GluN2B and nAChR-α7 were increased in the trained group; phosphorylated dopamine transporter levels were decreased in the trained group. D1 and GluN1 receptors were shown to be in the same complex. Taken together, distinct RCs were paralleling performance in the RAM which is relevant for interpretation of previous and design of future work on RCs in memory studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

    Science.gov (United States)

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2004-03-01

    There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

  5. The Role of the Prefrontal Cortex in Action Perception.

    Science.gov (United States)

    Raos, Vassilis; Savaki, Helen E

    2017-10-01

    In an attempt to shed light on the role of the prefrontal cortex in action perception, we used the quantitative 14C-deoxyglucose method to reveal the effects elicited by reaching-to-grasp in the light or in the dark and by observation of the same action executed by an external agent. We analyzed the cortical areas in the principal sulcus, the superior and inferior lateral prefrontal convexities and the orbitofrontal cortex of monkeys. We found that execution in the light and observation activated in common most of the lateral prefrontal and orbitofrontal cortical areas, with the exception of 9/46-dorsal activated exclusively for observation and 9/46-ventral, 11 and 13 activated only for execution. Execution in the dark implicated only the ventral bank of the principal sulcus and its adjacent inferior convexity along with areas 47/12-dorsal and 13, whereas execution in the light activated both banks of the principal sulcus and both superior and inferior convexities along with areas 10 and 11. Our results demonstrate that the prefrontal cortex integrates information in the service of both action generation and action perception, and are discussed in relation to its contribution in movement suppression during action observation and in attribution of action to the correct agent. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. The role of the medial prefrontal cortex in achieving goals.

    Science.gov (United States)

    Matsumoto, Kenji; Tanaka, Keiji

    2004-04-01

    Achieving goals in changing environments requires the course of action to be selected on the basis of goal expectation and memory of action-outcome contingency. It is often also essential to evaluate action on the basis of immediate outcomes and the discrimination of early action steps from the final step towards the goal. Recently, in single-cell recordings in monkeys, the neuronal activity that appears to underlie these processes has been noted in the medial part of the prefrontal cortex. Medial prefrontal cells were also active when the subjects extracted the rules of a task in a novel environment. The processes described above might play important roles in rule learning.

  7. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

    Science.gov (United States)

    Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

    2016-04-14

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  8. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Directory of Open Access Journals (Sweden)

    Joan F. Alonso

    2016-04-01

    Full Text Available Sleep deprivation (SD has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE. Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  9. The role of frontal EEG asymmetry in post-traumatic stress disorder

    NARCIS (Netherlands)

    Meyer, T.; Smeets, T.J.M.; Giesbrecht, T.; Quaedflieg, C.W.E.M.; Smulders, F.T.Y.; Meijer, E.H.; Merckelbach, H.L.G.J.

    2015-01-01

    Frontal alpha asymmetry, a biomarker derived from electroencephalography (EEG) recordings, has often been associated with psychological adjustment, with more left-sided frontal activity predicting approach motivation and lower levels of depression and anxiety. This suggests high relevance to

  10. Resting-state functional connectivity between right anterior insula and right orbital frontal cortex correlate with insight level in obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Jie Fan

    2017-01-01

    Full Text Available Few studies have explored the neurobiological basis of insight level in obsessive-compulsive disorder (OCD, though the salience network (SN has been implicated in insight deficits in schizophrenia. This study was then designed to investigate whether resting-state (rs functional connectivity (FC of SN was associated with insight level in OCD patients. We analyzed rs-functional magnetic resonance imaging (fMRI data from 21 OCD patients with good insight (OCD-GI, 19 OCD patients with poor insight (OCD-PI, and 24 healthy controls (HCs. Seed-based whole-brain FC and ROI (region of interest-wise connectivity analyses were performed with seeds/ROIs in the bilateral anterior insula (AI and dorsal anterior cingulate cortex (dACC. The right AI-right medial orbital frontal cortex (mOFC connectivity was found to be uniquely decreased in the OCD-PI group, and the value of this aberrant connectivity correlated with insight level in OCD patients. In addition, we found that the OCD-GI group had significantly increased right AI-left dACC connectivity within the SN, relative to HCs (overall trend for groups: OCD-GI > OCD-PI > HC. Our findings suggest that abnormal right AI-right mOFC FC may mediate insight deficits in OCD, perhaps due to impaired encoding and integration of self-evaluative information about OCD-related beliefs and behaviors. Our findings indicate a SN connectivity dissociation between OCD-GI and OCD-PI patients and support the notion of considering OCD-GI and OCD-PI as two distinct disorder subtypes.

  11. Medial prefrontal cortex role in recognition memory in rodents.

    Science.gov (United States)

    Morici, Juan Facundo; Bekinschtein, Pedro; Weisstaub, Noelia V

    2015-10-01

    The study of the neurobiology of recognition memory, defined by the integration of the different components of experiences that support recollection of past experiences have been a challenge for memory researches for many years. In the last twenty years, with the development of the spontaneous novel object recognition task and all its variants this has started to change. The features of recognition memory include a particular object or person ("what"), the context in which the experience took place, which can be the arena itself or the location within a particular arena ("where") and the particular time at which the event occurred ("when"). This definition instead of the historical anthropocentric one allows the study of this type of episodic memory in animal models. Some forms of recognition memory that require integration of different features recruit the medial prefrontal cortex. Focusing on findings from spontaneous recognition memory tasks performed by rodents, this review concentrates on the description of previous works that have examined the role that the medial prefrontal cortex has on the different steps of recognition memory. We conclude that this structure, independently of the task used, is required at different memory stages when the task cannot be solved by a single item strategy. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Virtual reality and the role of the prefrontal cortex in adults and children.

    Directory of Open Access Journals (Sweden)

    Lutz Jäncke

    2009-05-01

    Full Text Available In this review the neural underpinnings of the experience of presence are outlined. Firstly, it will be shown that presence is associated with an activation of a distributed network including the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Second, the dorsolateral prefrontal cortex (DLPFC is identified as a key node of this network in that it modulates the activity of this network and the associated experience of presence. Third, because of their unmatured frontal cortex, children lack the strong modulatory influence of the DLPFC on this network. Fourth, it is shown that by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS while participants are exposed to the virtual roller coaster ride presence-related measures are influenced. Finally, these findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out of body experiences.

  13. Recurrent long-lasting tethering reduces BDNF protein levels in the dorsal hippocampus and frontal cortex in pigs

    NARCIS (Netherlands)

    Vry, de J.; Prickaerts, J.; Jetten, M.; Hulst, M.M.; Steinbusch, H.W.M.; Hove, van den D.L.; Schuurman, T.; Staay, van der F.J.

    2012-01-01

    Brain-derived neurotrophic factor (BDNF) signaling has been implicated in the onset of depression and in antidepressant efficacy, although the exact role of this neurotrophin in the pathophysiology of depression remains to be elucidated. Also, the interaction between chronic stress, which may

  14. Neurophysiologic markers of primary motor cortex for laryngeal muscles and premotor cortex in caudal opercular part of inferior frontal gyrus investigated in motor speech disorder: a navigated transcranial magnetic stimulation (TMS) study.

    Science.gov (United States)

    Rogić Vidaković, Maja; Jerković, Ana; Jurić, Tomislav; Vujović, Igor; Šoda, Joško; Erceg, Nikola; Bubić, Andreja; Zmajević Schönwald, Marina; Lioumis, Pantelis; Gabelica, Dragan; Đogaš, Zoran

    2016-11-01

    Transcranial magnetic stimulation studies have so far reported the results of mapping the primary motor cortex (M1) for hand and tongue muscles in stuttering disorder. This study was designed to evaluate the feasibility of repetitive navigated transcranial magnetic stimulation (rTMS) for locating the M1 for laryngeal muscle and premotor cortical area in the caudal opercular part of inferior frontal gyrus, corresponding to Broca's area in stuttering subjects by applying new methodology for mapping these motor speech areas. Sixteen stuttering and eleven control subjects underwent rTMS motor speech mapping using modified patterned rTMS. The subjects performed visual object naming task during rTMS applied to the (a) left M1 for laryngeal muscles for recording corticobulbar motor-evoked potentials (CoMEP) from cricothyroid muscle and (b) left premotor cortical area in the caudal opercular part of inferior frontal gyrus while recording long latency responses (LLR) from cricothyroid muscle. The latency of CoMEP in control subjects was 11.75 ± 2.07 ms and CoMEP amplitude was 294.47 ± 208.87 µV, and in stuttering subjects CoMEP latency was 12.13 ± 0.75 ms and 504.64 ± 487.93 µV CoMEP amplitude. The latency of LLR in control subjects was 52.8 ± 8.6 ms and 54.95 ± 4.86 in stuttering subjects. No significant differences were found in CoMEP latency, CoMEP amplitude, and LLR latency between stuttering and control-fluent speakers. These results indicate there are probably no differences in stuttering compared to controls in functional anatomy of the pathway used for transmission of information from premotor cortex to the M1 cortices for laryngeal muscle representation and from there via corticobulbar tract to laryngeal muscles.

  15. The role of left posterior inferior temporal cortex in spelling.

    Science.gov (United States)

    Rapcsak, Steven Z; Beeson, Pélagie M

    2004-06-22

    To determine whether damage to left posterior inferior temporal cortex (PITC) is associated with agraphia and to characterize the nature of the spelling impairment. Left angular gyrus may play a critical role in spelling. However, this traditional view is challenged by reports of agraphia after left temporo-occipital lesions and by functional imaging studies demonstrating activation of left PITC during writing in normal individuals. Patients with focal damage to the left temporo-occipital cortex and normal control subjects were administered a comprehensive spelling battery that included regular words, irregular words, and nonwords as stimuli. Although patients performed worse than control subjects in all experimental conditions, the spelling deficit was particularly severe for irregular words, whereas regular word and nonword spelling were less impaired. Additional analyses indicated that orthographic regularity and word frequency had a much more pronounced effect on spelling accuracy in patients compared with control subjects. Most errors on irregular words were phonologically plausible, consistent with reliance on a sublexical phonologic spelling strategy (i.e., phoneme-grapheme conversion). Overall, the spelling impairment of the patients showed the characteristic profile of lexical agraphia. Lesion analyses indicated that the damage in the majority of patients encompassed an area within the left PITC (BA 37/20) where the authors previously obtained evidence of activation in a functional imaging study of writing in normal participants. The behavioral and neuroanatomic observations in the patients are consistent with functional imaging studies of writing in neurologically intact individuals and provide converging evidence for the role of left PITC in spelling. Together, these findings implicate left PITC as a possible neural substrate of the putative orthographic lexicon that contains stored memory representations for the written forms of familiar words.

  16. Unawareness of deficits in Alzheimer's disease: role of the cingulate cortex.

    Science.gov (United States)

    Amanzio, Martina; Torta, Diana M E; Sacco, Katiuscia; Cauda, Franco; D'Agata, Federico; Duca, Sergio; Leotta, Daniela; Palermo, Sara; Geminiani, Giuliano C

    2011-04-01

    Unawareness of deficits is a symptom of Alzheimer's disease that can be observed even in the early stages of the disease. The frontal hypoperfusion associated with reduced awareness of deficits has led to suggestions of the existence of a hypofunctioning prefrontal pathway involving the right dorsolateral prefrontal cortex, inferior parietal lobe, anterior cingulate gyri and limbic structures. Since this network plays an important role in response inhibition competence and patients with Alzheimer's disease who are unaware of their deficits exhibit impaired performance in response inhibition tasks, we predicted a relationship between unawareness of deficits and cingulate hypofunctionality. We tested this hypothesis in a sample of 29 patients with Alzheimer's disease (15 aware and 14 unaware of their disturbances), rating unawareness according to the Awareness of Deficit Questionnaire-Dementia scale. The cognitive domain was investigated by means of a wide battery including tests on executive functioning, memory and language. Neuropsychiatric aspects were investigated using batteries on behavioural mood changes, such as apathy and disinhibition. Cingulate functionality was assessed with functional magnetic resonance imaging, while patients performed a go/no-go task. In accordance with our hypotheses, unaware patients showed reduced task-sensitive activity in the right anterior cingulate area (Brodmann area 24) and in the rostral prefrontal cortex (Brodmann area 10). Unaware patients also showed reduced activity in the right post-central gyrus (Brodmann area 2), in the associative cortical areas such as the right parietotemporal-occipital junction (Brodmann area 39) and the left temporal gyrus (Brodmann areas 21 and 38), in the striatum and in the cerebellum. These findings suggest that the unawareness of deficits in early Alzheimer's disease is associated with reduced functional recruitment of the cingulofrontal and parietotemporal regions. Furthermore, in line with

  17. Aldehyde dehydrogenase 2 deficiency increases resting-state glutamate and expression of the GluN1 subunit of N-methyl-D-aspartate receptor in the frontal cortex of mice.

    Science.gov (United States)

    Jamal, Mostofa; Ono, Junichiro; Ameno, Kiyoshi; Shirakami, Gotaro; Tanaka, Naoko; Takakura, Ayaka; Kinoshita, Hiroshi

    2015-01-15

    Our previous study showed that Aldh2-knockout (Aldh2-KO) mice, an animal model of inactive aldehyde dehydrogenase 2 (ALDH2), have better spatial memory when compared with wild-type (WT) mice. Given that the neurotransmitter glutamate has been associated with learning and memory, the goal of the present study was to investigate whether the strain-dependent difference in spatial memory was associated with changes in glutamate transmitter levels or receptor function in the frontal cortex of Aldh2-KO and WT mice. Thus, we first measured extracellular glutamate levels in free-moving mice using microdialysis. Second, we studied protein expression of the N-methyl-D-aspartate (NMDA) receptor (GluN1) subunit and the α-amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) receptor (GluA1) subunit in lipid raft fractions using Western blot (WB). The samples were collected for WB, and lipid rafts were prepared from the insoluble fraction of homogenate tissue. Protein concentration was measured in the whole cell lysate (WCL) and in five separate lipid raft fractions. Cholesterol was also measured in all fractions 1-5. The microdialysis study revealed that basal glutamate concentration in the dialysates was approximately three-fold (0.27 ± 0.12 μM) higher in Aldh2-KO mice than in WT (0.10 ± 0.03 μM) mice. We also found an increase in the expression of GluN1 in Aldh2-KO mice compared with WT mice, both in the WCL and fraction 5, but GluA1 levels were unchanged as measured by WB. Our novel findings provide the first evidence for the role of ALDH2 in glutamate release and GluN1 protein expression in the frontal cortex. The observed strain differences in glutamate levels and GluN1 expression may suggest that enhanced glutamatergic function facilitates improved spatial memory in Aldh2-KO mice and such observation deserves further investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Contrasting the roles of the supplementary and frontal eye fields in ocular decision making.

    Science.gov (United States)

    Yang, Shun-Nan; Heinen, Stephen

    2014-06-15

    Single-unit recording in monkeys and functional imaging of the human frontal lobe indicate that the supplementary eye field (SEF) and the frontal eye field (FEF) are involved in ocular decision making. To test whether these structures have distinct roles in decision making, single-neuron activity was recorded from each structure while monkeys executed an ocular go/nogo task. The task rule is to pursue a moving target if it intersects a visible square or "go zone." We found that most SEF neurons showed differential go/nogo activity during the delay period, before the target intersected the go zone (delay period), whereas most FEF neurons did so after target intersection, during the period in which the movement was executed (movement period). Choice probability (CP) for SEF neurons was high in the delay period but decreased in the movement period, whereas for FEF neurons it was low in the delay period and increased in the movement period. Directional selectivity of SEF neurons was low throughout the trial, whereas that of FEF neurons was highest in the delay period, decreasing later in the trial. Increasing task difficulty led to later discrimination between go and nogo in both structures and lower CP in the SEF, but it did not affect CP in the FEF. The results suggest that the SEF interprets the task rule early but is less involved in executing the motor decision than is the FEF and that these two areas collaborate dynamically to execute ocular decisions. Copyright © 2014 the American Physiological Society.

  19. T'ain't what you say, it's the way that you say it--left insula and inferior frontal cortex work in interaction with superior temporal regions to control the performance of vocal impersonations.

    Science.gov (United States)

    McGettigan, Carolyn; Eisner, Frank; Agnew, Zarinah K; Manly, Tom; Wisbey, Duncan; Scott, Sophie K

    2013-11-01

    Historically, the study of human identity perception has focused on faces, but the voice is also central to our expressions and experiences of identity [Belin, P., Fecteau, S., & Bedard, C. Thinking the voice: Neural correlates of voice perception. Trends in Cognitive Sciences, 8, 129-135, 2004]. Our voices are highly flexible and dynamic; talkers speak differently, depending on their health, emotional state, and the social setting, as well as extrinsic factors such as background noise. However, to date, there have been no studies of the neural correlates of identity modulation in speech production. In the current fMRI experiment, we measured the neural activity supporting controlled voice change in adult participants performing spoken impressions. We reveal that deliberate modulation of vocal identity recruits the left anterior insula and inferior frontal gyrus, supporting the planning of novel articulations. Bilateral sites in posterior superior temporal/inferior parietal cortex and a region in right middle/anterior STS showed greater responses during the emulation of specific vocal identities than for impressions of generic accents. Using functional connectivity analyses, we describe roles for these three sites in their interactions with the brain regions supporting speech planning and production. Our findings mark a significant step toward understanding the neural control of vocal identity, with wider implications for the cognitive control of voluntary motor acts.

  20. Distinct changes in CREB phosphorylation in frontal cortex and striatum during contingent and non-contingent performance of a visual attention task

    Directory of Open Access Journals (Sweden)

    Mirjana eCarli

    2011-10-01

    Full Text Available The cyclic-AMP response element binding protein (CREB family of transcription factors has been implicated in numerous forms of behavioural plasticity. We investigated CREB phosphorylation along some nodes of corticostriatal circuitry such as frontal cortex (FC and dorsal (caudate putamen, CPu and ventral (nucleus accumbens, NAC striatum in response to the contingent or non-contingent performance of the five-choice serial reaction time task (5-CSRTT used to assess visuospatial attention. Three experimental manipulations were used; an attentional performance group (contingent, master, a group trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished (non-contingent, yoked and a control group matched for food deprivation and exposure to the test apparatus (untrained. Rats trained on the 5-CSRTT (both master and yoked had higher levels of CREB protein in the FC, CPu and NAC compared to untrained controls. Despite the divergent behaviour of master and yoked rats CREB activity in the FC was not substantially different. In rats performing the 5-CSRTT (master, CREB activity was completely abolished in the CPu whereas in the NAC it remained unchanged. In contrast, CREB phosphorylation in CPu and NAC increased only when the contingency changed from goal-dependent to goal-independent reinforcement (yoked. The present results indicate that up-regulation of CREB protein expression across cortical and striatal regions possibly reflects the extensive instrumental learning and performance whereas increased CREB activity in striatal regions may signal the unexpected change in the relationship between instrumental action and reinforcement.

  1. Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment.

    Science.gov (United States)

    Franzmeier, Nicolai; Göttler, Jens; Grimmer, Timo; Drzezga, Alexander; Áraque-Caballero, Miguel A; Simon-Vermot, Lee; Taylor, Alexander N W; Bürger, Katharina; Catak, Cihan; Janowitz, Daniel; Müller, Claudia; Duering, Marco; Sorg, Christian; Ewers, Michael

    2017-01-01

    Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer's disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

  2. Frontal cortex electrophysiology in reward- and punishment-related feedback processing during advice-guided decision making: An interleaved EEG-DC stimulation study.

    Science.gov (United States)

    Wischnewski, Miles; Bekkering, Harold; Schutter, Dennis J L G

    2018-04-01

    During decision making, individuals are prone to rely on external cues such as expert advice when the outcome is not known. However, the electrophysiological correlates associated with outcome uncertainty and the use of expert advice are not completely understood. The feedback-related negativity (FRN), P3a, and P3b are event-related brain potentials (ERPs) linked to dissociable stages of feedback and attentional processing during decision making. Even though these ERPs are influenced by both reward- and punishment-related feedback, it remains unclear how extrinsic information during uncertainty modulates these brain potentials. In this study, the effects of advice cues on decision making were investigated in two separate experiments. In the first experiment, electroencephalography (EEG) was recorded in healthy volunteers during a decision-making task in which the participants received reward or punishment feedback preceded by novice, amateur, or expert advice. The results showed that the P3a component was significantly influenced by the subjective predictive value of an advice cue, whereas the FRN and P3b were unaffected by the advice cues. In the second, sham-controlled experiment, cathodal transcranial direct current stimulation (ctDCS) was administered in conjunction with EEG in order to explore the direct contributions of the frontal cortex to these brain potentials. Results showed no significant change in either advice-following behavior or decision times. However, ctDCS did decrease FRN amplitudes as compared to sham, with no effect on the P3a or P3b. Together, these findings suggest that advice information may act primarily on attention allocation during feedback processing, whereas the electrophysiological correlates of the detection and updating of internal prediction models are not affected.

  3. Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Nicolai Franzmeier

    2017-08-01

    Full Text Available Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44. Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education and better maintenance of memory in mild cognitive impairment (MCI. Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC and in an independent validation sample (23 MCI/32 HC. Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN, but positively correlated with the dorsal-attention network (DAN. Greater education predicted stronger LFC-DMN-connectivity (anti-correlation and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

  4. DOES THE INFERIOR FRONTAL SULCUS PLAY A FUNCTIONAL ROLE IN DECEPTION? A NEURONAVIGATED THETA-BURST TRANSCRANIAL MAGNETIC STIMULATION STUDY

    Directory of Open Access Journals (Sweden)

    Bruno eVerschuere

    2012-10-01

    Full Text Available Background. By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. Objective. We critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. Method. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS by means of neuronavigated continuous theta burst stimulation (cTBS. Individual structural magnetic resonance brain images (MRI were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Results. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. Conclusions. The present findings do not support the hypothesis that the right inferior frontal sulcus is critically involved in deception.

  5. The role of frontal-subcortical circuits in the development of obsessive-compulsive disorders

    Directory of Open Access Journals (Sweden)

    M. A. Kutlubaev

    2016-01-01

    Full Text Available The paper presents a concise review of investigations into the role of impaired frontal-subcortical circuits in the development of obsessive-compulsive disorder (OCD. It gives data on the frequency of neurosis-like symptoms of the OCD spectrum in neurological diseases.The development of OCD is associated with an imbalance between the activity of the direct (activating and indirect (inhibitory pathways of the cortico-striatal-thalamo-cortical feedback loop. These data are confirmed by the results of neuroimaging and neuropsychological studies in patients with OCD. The frequency of OCD symptoms is high in organic brain lesions. OCP may be a manifestation of neurological diseases so their timely detection is an important aspect of a neurologist's work. The treatment of patients with neurosis-like disorders of the OCD spectrum within neurological diseases requires a multidisciplinary approach with the participation of a neurologist, a psychiatrist/psychotherapist, and a psychologist. It is necessary to combine pathogenetic treatment of the underlying disease and its neurosis-like manifestations. 

  6. Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions.

    Science.gov (United States)

    Goard, Michael J; Pho, Gerald N; Woodson, Jonathan; Sur, Mriganka

    2016-08-04

    Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution.

  7. Transcranial Direct Current Stimulation of the Temporoparietal Junction and Inferior Frontal Cortex Improves Imitation-Inhibition and Perspective-Taking with no Effect on the Autism-Spectrum Quotient Score

    Directory of Open Access Journals (Sweden)

    Satoshi Nobusako

    2017-05-01

    Full Text Available Lesions to brain regions such as the temporoparietal junction (TPJ and inferior frontal cortex (IFC are thought to cause autism-spectrum disorder (ASD. Previous studies indicated that transcranial direct current stimulation (tDCS of the right TPJ improves social cognitive functions such as imitation-inhibition and perspective-taking. Although previous work shows that tDCS of the right IFC improves imitation-inhibition, its effects on perspective-taking have yet to be determined. In addition, the role of the TPJ and IFC in determining the Autism-Spectrum Quotient (AQ, which is a measure of autism spectrum traits, is still unclear. Thus, the current study performed tDCS on the right TPJ and the right IFC of healthy adults, and examined its effects on imitation-inhibition, perspective-taking and AQ scores. Based on previous studies, we hypothesized that anodal tDCS of the right IFC and right TPJ would improve imitation-inhibition, perspective-taking and the AQ score. Anodal tDCS of the right TPJ or IFC significantly decreased the interference effect in an imitation-inhibition task and the cost of perspective-taking in a perspective-taking task, in comparison to the sham stimulation control. These findings indicated that both the TPJ and the IFC play a role in imitation-inhibition and perspective-taking, i.e., control of self and other representations. However, anodal stimulation of the right TPJ and the right IFC did not alter participants’ AQ. This finding conflicts with results from previous brain imaging studies, which could be attributed to methodological differences such as variation in sex, age and ASD. Therefore, further research is necessary to determine the relationship between the TPJ and IFC, and the AQ.

  8. The Causal Role of the Prefrontal Cortex and Somatosensory Cortex in Tactile Working Memory.

    Science.gov (United States)

    Zhao, Di; Zhou, Yong-Di; Bodner, Mark; Ku, Yixuan

    2017-08-22

    In the present study, we searched for causal evidence linking activity in the bilateral primary somatosensory cortex (SI), posterior parietal cortex (PPC), and prefrontal cortex (PFC) with behavioral performance in vibrotactile working memory. Participants performed a vibrotactile delayed matching-to-sample task, while single-pulse transcranial magnetic stimulation (sp-TMS) was applied over these cortical areas at 100, 200, 300, 600, 1600, and 1900 ms after the onset of vibrotactile stimulation (200 ms duration). In our experiments, sp-TMS over the contralateral SI at the early delay (100 and 200 ms) deteriorated the accuracy of task performance, and over the ipsilateral SI at the late delay (1600 and 1900 ms) also induced such deteriorating effects. Furthermore, deteriorating effects caused by sp-TMS over the contralateral DLPFC at the same maintenance stage (1600 ms) were correlated with the effects caused by sp-TMS over the ipsilateral SI, indicating that information retained in the ipsilateral SI during the late delay may be associated with the DLPFC. Taken together, these results suggest that both the contralateral and ipsilateral SIs are involved in tactile WM, and the contralateral DLPFC bridges the contralateral SI and ipsilateral SI for goal-directed action. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. DETACHING FROM THE NEGATIVE BY REAPPRAISAL: THE ROLE OF RIGHT SUPERIOR FRONTAL GYRUS (BA9/32

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    Rosalux eFalquez

    2014-05-01

    Full Text Available The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself, i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and grey matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM analysis to identify deficit related areas (ROI. Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM analysis was run, in which healthy participant’s REAPPself ability scores were correlated with grey matter intensities. Results showed that 1 regions in the right superior frontal gyrus (SFG, comprising the right dorsolateral prefrontal cortex (BA9 and the right dorsal anterior cingulate cortex (BA32, were associated with patient’s impaired down-regulation of arousal, 2 a lesion in the depicted ROI occasioned significant REAPPself impairments, 3 REAPPself ability of controls was linked with increased grey matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32 might be indispensable for REAPPself. Implications for neurofeedback research

  10. Neural mechanisms of memory retrieval: role of the prefrontal cortex.

    Science.gov (United States)

    Hasegawa, I

    2000-01-01

    In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys. When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres. Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input. In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks. Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

  11. Predicting treatment response in schizophrenia: The role of striatal and frontal dopamine D2/D3 receptor binding potential

    DEFF Research Database (Denmark)

    Nørbak, Henrik; Wulff, Sanne; Nielsen, Mette Ødegaard

    included 25 patients. The ligand [123I]epidepride was used for quantification of extrastriatal dopamine D2/D3 receptors. Patients were randomised to twelve weeks of treatment with either risperidone or zuclopenthixol. Results: In the IBZMcohort the mean PANSS total score was 79 at baseline and 65 at follow...... group (Rho=-0,417 P=0,060). In the EPIcohort the mean PANSS total score was 70 at baseline and 48 at follow up. In the frontal cortex we found a positive correlation (Rho=0.56 P=0.003) between BP and change in positive symptom score for the whole group as well as in the subgroup treated with risperidone...

  12. Language and alexithymia: Evidence for the role of the inferior frontal gyrus in acquired alexithymia.

    Science.gov (United States)

    Hobson, Hannah; Hogeveen, Jeremy; Brewer, Rebecca; Catmur, Caroline; Gordon, Barry; Krueger, Frank; Chau, Aileen; Bird, Geoffrey; Grafman, Jordan

    2018-03-01

    The clinical relevance of alexithymia, a condition associated with difficulties identifying and describing one's own emotion, is becoming ever more apparent. Increased rates of alexithymia are observed in multiple psychiatric conditions, and also in neurological conditions resulting from both organic and traumatic brain injury. The presence of alexithymia in these conditions predicts poorer regulation of one's emotions, decreased treatment response, and increased burden on carers. While clinically important, the aetiology of alexithymia is still a matter of debate, with several authors arguing for multiple 'routes' to impaired understanding of one's own emotions, which may or may not result in distinct subtypes of alexithymia. While previous studies support the role of impaired interoception (perceiving bodily states) in the development of alexithymia, the current study assessed whether acquired language impairment following traumatic brain injury, and damage to language regions, may also be associated with an increased risk of alexithymia. Within a sample of 129 participants with penetrating brain injury and 33 healthy controls, neuropsychological testing revealed that deficits in a non-emotional language task, object naming, were associated with alexithymia, specifically with difficulty identifying one's own emotions. Both region-of-interest and whole-brain lesion analyses revealed that damage to language regions in the inferior frontal gyrus was associated with the presence of both this language impairment and alexithymia. These results are consistent with a framework for acquired alexithymia that incorporates both interoceptive and language processes, and support the idea that brain injury may result in alexithymia via impairment in any one of a number of more basic processes. Copyright © 2018. Published by Elsevier Ltd.

  13. Frontal-subcortical circuits in obsessive-compulsive disorder: role of the dopamine D1 receptor

    International Nuclear Information System (INIS)

    Olver, J.S.; Reutens, D.C.; Maruff, P.; Burrows, G.D.; Norman, T.R.; Ellen, S.R.; Pantelis, C.; Tochon-Danguy, H.; Ackermann, U.; Stekelenberg, N.

    2000-01-01

    Full text: Obsessive-Compulsive Disorder (OCD) is an anxiety disorder which is increasingly being recognised as a neurobiological disorder. While serotonergic mechanisms have been proposed, the major competing theory in the pathophysiology of OCD involves the neurotransmitter dopamine. The Dopamine D1 receptor is implicated in OCD following the finding of specific spatial working memory abnormalities in a series of neuropsychological studies. Spatial working memory is known to depend on the integrity of D1 receptor function in the Dorso-lateral Prefrontal Cortex (DLPFC) of primates. This study aims to examine the role of dopamine in patients with OCD and in particular to test the hypothesis that there is an upregulation of dopamine D1 receptors in the DLPFC which correlates with spatial working memory deficits in OCD. Three OCD patients and three normal controls underwent Positron Emission Tomography (PET) following intravenous injection of the D1 antagonist PET ligand SCH23390. Reconstructed PET images were co registered with subject Magnetic Resonance Images (MRI) and regions of interest drawn manually. We will present the analysis of the Binding Potentials of SCH23390 in the regions of interest of the first three OCD patients and compare them with three normal control patients. In conclusion Dopamine-Serotonergic interactions are involved in the pathophysiology of OCD. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  14. Imagery of a moving object: the role of occipital cortex and human MT/V5+.

    Science.gov (United States)

    Kaas, Amanda; Weigelt, Sarah; Roebroeck, Alard; Kohler, Axel; Muckli, Lars

    2010-01-01

    Visual imagery--similar to visual perception--activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short-term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral-occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1-3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences.

  15. Behavioural changes after ablation of subdivisions of the rat prefrontal cortex

    DEFF Research Database (Denmark)

    Mogensen, Jesper; Divac, Ivan

    1993-01-01

    Neurobiologi, præfrontal cortex, exploration, betinget smagsaversion, spontan alternation, operant udslukning......Neurobiologi, præfrontal cortex, exploration, betinget smagsaversion, spontan alternation, operant udslukning...

  16. The role of the ventromedial prefrontal cortex in memory consolidation

    NARCIS (Netherlands)

    Nieuwenhuis, I.L.C.; Takashima, A.

    2011-01-01

    System-level memory consolidation theory posits that the hippocampus initially links the neocortical representations, followed by a shift to a hippocampus-independent neocortical network. With consolidation, an increase in activity in the human subgenual ventromedial prefrontal cortex (vmPFC) has

  17. The Role of Secondary Frontal Waves in Causing Missed or False Alarm Flood Forecasts During Landfalling Atmospheric Rivers

    Science.gov (United States)

    Martin, A.; Ralph, F. M.; Lavers, D. A.; Kalansky, J.; Kawzenuk, B.

    2015-12-01

    The previous ten years has seen an explosion in research devoted to the Atmospheric River (AR) phenomena, features of the midlatitude circulation responsible for large horizontal water vapor transport. Upon landfall, ARs can be associated with 30-50% of annual precipitation in some regions, while also causing the largest flooding events in places such as coastal California. Little discussed is the role secondary frontal waves play in modulating precipitation during a landfalling AR. Secondary frontal waves develop along an existing cold front in response to baroclinic frontogenesis, often coinciding with a strong upper-tropospheric jet. If the secondary wave develops along a front associated with a landfalling AR, the resulting precipitation may be much greater or much less than originally forecasted - especially in regions where orographic uplift of horizontally transported water vapor is responsible for a large portion of precipitation. In this study, we present several cases of secondary frontal waves that have occurred in conjunction with a landfalling AR on the US West Coast. We put the impact of these cases in historical perspective using quantitative precipitation forecasts, satellite data, reanalyses, and estimates of damage related to flooding. We also discuss the dynamical mechanisms behind secondary frontal wave development and relate these mechanisms to the high spatiotemporal variability in precipitation observed during ARs with secondary frontal waves. Finally, we demonstrate that even at lead times less than 24 hours, current quantitative precipitation forecasting methods have difficulty accurately predicting the rainfall in the area near the secondary wave landfall, in some cases leading to missed or false alarm flood warnings, and suggest methods which may improve quantitative precipitation forecasts for this type of system in the future.

  18. The role of the midcingulate cortex in monitoring others’ decisions

    Directory of Open Access Journals (Sweden)

    Matthew A J Apps

    2013-12-01

    Full Text Available A plethora of research has implicated the cingulate cortex in the processing of social information (i.e. processing elicited by, about, and directed towards others and reward-related information that guides decision-making. However, it is often overlooked that there is variability in the cytoarchitectonic properties and anatomical connections across the cingulate cortex, which is indicative of functional variability. Here we review evidence from lesion, single-unit recording and functional imaging studies. Taken together, these support the claim that the processing of information that has the greatest influence on social behaviour can be localised to the gyral surface of the midcingulate cortex (MCCg. We propose that the MCCg is engaged when predicting and monitoring the outcomes of decisions during social interactions. In particular, the MCCg processes statistical information that tracks the extent to which the outcomes of decisions meet goals when interacting with others. We provide a novel framework for the computational mechanisms that underpin such social information processing in the MCCg. This framework provides testable hypotheses for the social deficits displayed in autism spectrum disorders and psychopathy.

  19. Expression profiles of mitochondrial genes in the frontal cortex and the caudate nucleus of developing humans and mice selectively bred for high and low fear.

    Directory of Open Access Journals (Sweden)

    Kwang H Choi

    Full Text Available A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC and the caudate nucleus (CN of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115 and the CN (117 are associated with the GO term: mitochondrion (FDR qv <0.05. A greater number of the genes in the PFC (91% than the genes in the CN (62% showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB, NADH dehydrogenase flavoprotein (NDUFV1, mitochondrial uncoupling protein 5 (SLC25A14 and tubulin beta-3 chain (TUBB3. In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05. However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

  20. Memory of music: roles of right hippocampus and left inferior frontal gyrus.

    Science.gov (United States)

    Watanabe, Takamitsu; Yagishita, Sho; Kikyo, Hideyuki

    2008-01-01

    We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

  1. Time organization of frontal-motor cortex interneuron interactions in the cat neocortex in conditions of different levels of food motivation.

    Science.gov (United States)

    Merzhanova, G Kh; Dolbakyan, E E

    1997-01-01

    Studies were carried out in conscious cats with recording of multicellular activity in moderate hunger and after 24-h food deprivation. Cross-correlation analysis was used to assess statistical interneuron interactions between closely-located neurons in the frontal and sensorimotor regions of the neocortex (local networks), and between the cells of these regions (distributed networks). One-day food deprivation increased the number of interactions formed within both local and distributed neuron networks. Increases in intercortical connections between the frontal and motor regions was seen at all time intervals studied (0-100 msec), though the most significant changes occurred at time intervals of up to 30 msec.

  2. ROLE OF YOGA IN ALIENATING THE MEMORY DECLINE AND FRONTAL LOBE METABOLITE CHANGES IN TYPE 2 DIABETES.

    Science.gov (United States)

    Santhakumari, Rajani; Reddy, Indla Yogananda; Archana, R; Rajesh, P

    2016-01-01

    Recent research studies have established the fact, that glycosylation is causing the memory decline and this is further supported by the alteration of brain metabolite concentrations in diabetes. The present study is hypothesized that yoga is having alienating ability of memory decline and alteration of frontal lobe metabolite concentrations, which are the result of glycosylation in type 2 diabetes. Five type 2 diabetic subjects of both the sex, aged between 35-55 years, who practiced yoga over a period of six months in a yoga institute, were recruited as test group. Age and sex matched five type 2 diabetic subjects were recruited as control group, both the group subjects are on oral hypoglycaemic agents. Glycosylated haemoglobin percentage was estimated with Bio-Rad instrument, frontal lobe metabolites were estimated with Proton Magnetic Resonance Spectroscopy (H-MRS), memory was calculated with PGI-Memory Scale (PGIMS) that is a part of PGI-Battery of Brain Dysfunction (PGI-BBD), which is a neuropsychological battery. Mean glycosylated haemoglobin percentage and memory dysfunction rating in control and test group subjects are 6.9±0.4 & 7.8±1.84 (p=0.03), and 14±1& 6±1 (p=0.0001) respectively. Right and left frontal lobe N-Acetyl Aspartate (NAA) and Myoionositol (mI) concentrations were more or less similar in both the groups. Yoga is having a significant role in alienating the decline in memory caused by glycosylation in type 2 diabetes but not on the alteration of frontal lobe NAA and mI concentrations.

  3. Is there a role of visual cortex in spatial hearing?

    Science.gov (United States)

    Zimmer, Ulrike; Lewald, Jörg; Erb, Michael; Grodd, Wolfgang; Karnath, Hans-Otto

    2004-12-01

    The integration of auditory and visual spatial information is an important prerequisite for accurate orientation in the environment. However, while visual spatial information is based on retinal coordinates, the auditory system receives information on sound location in relation to the head. Thus, any deviation of the eyes from a central position results in a divergence between the retinal visual and the head-centred auditory coordinates. It has been suggested that this divergence is compensated for by a neural coordinate transformation, using a signal of eye-in-head position. Using functional magnetic resonance imaging, we investigated which cortical areas of the human brain participate in such auditory-visual coordinate transformations. Sounds were produced with different interaural level differences, leading to left, right or central intracranial percepts, while subjects directed their gaze to visual targets presented to the left, to the right or straight ahead. When gaze was to the left or right, we found the primary visual cortex (V1/V2) activated in both hemispheres. The occipital activation did not occur with sound lateralization per se, but was found exclusively in combination with eccentric eye positions. This result suggests a relation of neural processing in the visual cortex and the transformation of auditory spatial coordinates responsible for maintaining the perceptual alignment of audition and vision with changes in gaze direction.

  4. The role of human ventral visual cortex in motion perception

    Science.gov (United States)

    Saygin, Ayse P.; Lorenzi, Lauren J.; Egan, Ryan; Rees, Geraint; Behrmann, Marlene

    2013-01-01

    Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion. PMID:23983030

  5. Distinct roles of left inferior frontal regions that explain individual differences in second language acquisition.

    Science.gov (United States)

    Sakai, Kuniyoshi L; Nauchi, Arihito; Tatsuno, Yoshinori; Hirano, Kazuyoshi; Muraishi, Yukimasa; Kimura, Masakazu; Bostwick, Mike; Yusa, Noriaki

    2009-08-01

    Second language (L2) acquisition is more susceptible to environmental and idiosyncratic factors than first language acquisition. Here, we used functional magnetic resonance imaging for L2 learners of different ages of first exposure (mean: 12.6 and 5.6 years) in a formal school environment, and compared the cortical activations involved in processing English sentences containing either syntactic or spelling errors, where the testing ages and task performances of both groups were matched. We found novel activation patterns in two regions of the left inferior frontal gyrus (IFG) that correlated differentially with the performances of the late and early learners. Specifically, activations of the dorsal and ventral triangular part (F3t) of the left IFG correlated positively with the accuracy of the syntactic task for the late learners, whereas activations of the left ventral F3t correlated negatively with the accuracy for the early learners. In contrast, other cortical regions exhibited differential correlation patterns with the reaction times (RTs) of the syntactic task. Namely, activations of the orbital part (F3O) of the left IFG, as well as those of the left angular gyrus, correlated positively with the RTs for the late learners, whereas those activations correlated negatively with the RTs for the early learners. Moreover, the task-selective activation of the left F3O was maintained for both the late and early learners. These results explain individual differences in L2 acquisition, such that the acquisition of linguistic knowledge in L2 is subserved by at least two distinct inferior frontal regions of the left F3t and F3O. (c) 2008 Wiley-Liss, Inc.

  6. The role of the epidermis and cortex in gravitropic curvature of maize roots

    Science.gov (United States)

    Bjorkman, T.; Cleland, R. E.

    1988-01-01

    In order to determine the role of the epidermis and cortex in gravitropic curvature of seedling roots of maize (Zea mays L. cv. Merit), the cortex on the two opposite flanks was removed from the meristem through the growing zone; gravitropic curvature was measured with the roots oriented horizontally with the cut flanks either on the upper and lower side, or on the lateral sides as a wound control. Curvature was slower in both these treatments (53 degrees in 5 h) than in intact roots (82 degrees), but there was no difference between the two orientations in extent and rate of curvature, nor in the latent time, showing that epidermis and cortex were not the site of action of the growth-regulating signal. The amount of cortex removed made no difference in the extent of curvature. Curvature was eliminated when the endodermis was damaged, raising the possibility that the endodermis or the stele-cortex interface controls gravitropic curvature in roots. The elongation rate of roots from which just the epidermis had been peeled was reduced by 0.01 mM auxin (indole-3-acetic acid) from 0.42 to 0.27 mm h-1, contradicting the hypothesis that only the epidermis responds to changes in auxin activity during gravistimulation. These observations indicate that gravitropic curvature in maize roots is not driven by differential cortical cell enlargement, and that movement of growth regulator(s) from the tip to the elongating zone is unlikely to occur in the cortex.

  7. The role of the medial prefrontal cortex in trace fear extinction

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that supports extinction of this memory has received very little attention. Recent research has indicated that trace fear extinction requires a different neural circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ. PMID:25512576

  8. Similar or different? The role of the ventrolateral prefrontal cortex in similarity detection.

    Directory of Open Access Journals (Sweden)

    Béatrice Garcin

    Full Text Available Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., "both have peel", while others continue to look for differences between these objects (e.g., "one is yellow, the other is orange". These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC. We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1 Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2 Abstraction per se activates the left dorsolateral PFC.

  9. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. ¹H-NMR Spectroscopy Study.

    Science.gov (United States)

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-10-15

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (¹H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission--Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.

  10. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectroscopy Study

    Science.gov (United States)

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-01-01

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology. PMID:26501256

  11. Frontal midline theta oscillations during mental arithmetic: effects of stress

    OpenAIRE

    Gärtner, Matti; Grimm, Simone; Bajbouj, Malek

    2015-01-01

    Complex cognitive tasks such as mental arithmetic heavily rely on intact, well-coordinated prefrontal cortex (PFC) function. Converging evidence suggests that frontal midline theta (FMT) oscillations play an important role during the execution of such PFC-dependent tasks. Additionally, it is well-established that acute stress impairs PFC function, and recent evidence suggests that FMT is decreased under stress. In this EEG study, we investigated FMT oscillations during a mental arithmetic tas...

  12. Prefrontal Cortex: Role in Acquisition of Overlapping Associations and Transitive Inference

    Science.gov (United States)

    DeVito, Loren M.; Lykken, Christine; Kanter, Benjamin R.; Eichenbaum, Howard

    2010-01-01

    "Transitive inference" refers to the ability to judge from memory the relationships between indirectly related items that compose a hierarchically organized series, and this capacity is considered a fundamental feature of relational memory. Here we explored the role of the prefrontal cortex in transitive inference by examining the performance of…

  13. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    Science.gov (United States)

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  14. Auditory Connections and Functions of Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Bethany ePlakke

    2014-07-01

    Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

  15. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  16. Pivotal role of anterior cingulate cortex in working memory after traumatic brain injury in youth

    Directory of Open Access Journals (Sweden)

    Fabienne eCazalis

    2011-01-01

    Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.

  17. Exploring the role of white matter connectivity in cortex maturation.

    Directory of Open Access Journals (Sweden)

    Cecilia L Friedrichs-Maeder

    Full Text Available The maturation of the cortical gray matter (GM and white matter (WM are described as sequential processes following multiple, but distinct rules. However, neither the mechanisms driving brain maturation processes, nor the relationship between GM and WM maturation are well understood. Here we use connectomics and two MRI measures reflecting maturation related changes in cerebral microstructure, namely the Apparent Diffusion Coefficient (ADC and the T1 relaxation time (T1, to study brain development. We report that the advancement of GM and WM maturation are inter-related and depend on the underlying brain connectivity architecture. Particularly, GM regions and their incident WM connections show corresponding maturation levels, which is also observed for GM regions connected through a WM tract. Based on these observations, we propose a simple computational model supporting a key role for the connectome in propagating maturation signals sequentially from external stimuli, through primary sensory structures to higher order functional cortices.

  18. The prefrontal cortex and variants of sequential behaviour: indications of functional differentiation between subdivisions of the rat's prefrontal cortex

    DEFF Research Database (Denmark)

    Mogensen, Jesper; Holm, Søren

    1994-01-01

    Neurobiologi, præfrontal cortex, sekventiel adfærd, rotte, adfærdsprogrammering, informationsbearbejdning......Neurobiologi, præfrontal cortex, sekventiel adfærd, rotte, adfærdsprogrammering, informationsbearbejdning...

  19. Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

    Science.gov (United States)

    Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

    2018-01-24

    Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

  20. Auditory enhancement of visual memory encoding is driven by emotional content of the auditory material and mediated by superior frontal cortex.

    Science.gov (United States)

    Proverbio, A M; De Benedetto, F

    2018-02-01

    The aim of the present study was to investigate how auditory background interacts with learning and memory. Both facilitatory (e.g., "Mozart effect") and interfering effects of background have been reported, depending on the type of auditory stimulation and of concurrent cognitive tasks. Here we recorded event related potentials (ERPs) during face encoding followed by an old/new memory test to investigate the effect of listening to classical music (Čajkovskij, dramatic), environmental sounds (rain) or silence on learning. Participants were 15 healthy non-musician university students. Almost 400 (previously unknown) faces of women and men of various age were presented. Listening to music during study led to a better encoding of faces as indexed by an increased Anterior Negativity. The FN400 response recorded during the memory test showed a gradient in its amplitude reflecting face familiarity. FN400 was larger to new than old faces, and to faces studied during rain sound listening and silence than music listening. The results indicate that listening to music enhances memory recollection of faces by merging with visual information. A swLORETA analysis showed the main involvement of Superior Temporal Gyrus (STG) and medial frontal gyrus in the integration of audio-visual information. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation

    Directory of Open Access Journals (Sweden)

    Alessandro eGrecucci

    2013-09-01

    Full Text Available Previous studies have reported the effect of emotion regulation strategies on both individual and social decision making, however the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer’s intentions as more negative, down-regulation (reappraising the proposer’s intentions as less negative, as well as a baseline ‘look’ condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, regulating regions were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, regulated regions were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners’ behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal emotion regulation strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others’ intentions may affect the way we emotionally react.

  2. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation.

    Science.gov (United States)

    Grecucci, Alessandro; Giorgetta, Cinzia; Bonini, Nicolao; Sanfey, Alan G

    2013-01-01

    Previous studies have reported the effect of emotion regulation (ER) strategies on both individual and social decision-making, however, the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game (DG) in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline "look" condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, "regulating regions") were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, "regulated regions") were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners' behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal ER strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others' intentions may affect the way we emotionally react.

  3. Role of the Sensorimotor Cortex in Tourette Syndrome using Multimodal Imaging

    OpenAIRE

    Tinaz, Sule; Belluscio, Beth A.; Malone, Patrick; van der Veen, Jan Willem; Hallett, Mark; Horovitz, Silvina G.

    2014-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. ...

  4. Differential Activation of Fast-Spiking and Regular-Firing Neuron Populations During Movement and Reward in the Dorsal Medial Frontal Cortex

    Science.gov (United States)

    Insel, Nathan; Barnes, Carol A.

    2015-01-01

    The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory–excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state. PMID:24700585

  5. Lifelong plasticity in the rat auditory cortex: basic mechanisms and role of sensory experience.

    Science.gov (United States)

    de Villers-Sidani, Etienne; Merzenich, Michael M

    2011-01-01

    The rodent auditory cortex has provided a particularly useful model for studying cortical plasticity phenomenology and mechanisms, both in infant and in adult animal models. Much of our initial understanding of the neurological processes underlying learning-induced changes in the cortex stems from the early exploitation of this model. More recent studies have provided a rich and elaborate demonstration of the "rules" governing representational plasticity induced during the critical period (CP) and in the longer post-CP "adult" plasticity epoch. These studies have also contributed importantly to the application of these "rules" to the development of practical training tools designed to improve the functional capacities of the auditory, language, and reading capacities of both children with developmental impairments and adults with acquired impairments in the auditory/aural speed and related cognitive domains. Using age as a connecting thread, we review recent studies performed in the rat primary auditory cortex (A1) that have provided further insight into the role of sensory experience in the shaping auditory signal representations, and into their possible role in shaping the machinery that regulates "adult" plasticity in A1. With this background, the role of auditory training in the remediation of auditory processing impairments is briefly discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Maladaptive Sexual Behavior Following Concurrent Methamphetamine and Sexual Experience in Male Rats is Associated with Altered Neural Activity in Frontal Cortex.

    Science.gov (United States)

    Kuiper, Lindsey B; Frohmader, Karla S; Coolen, Lique M

    2017-09-01

    The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior in male rats and the effects of concurrent Meth and sexual behavior on neural activity, using ERK phosphorylation (pERK). First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm increased pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala. Second, effects of concurrent Meth and sex experience were tested in males that were exposed to four daily sessions of concurrent Meth (1 mg/kg) or saline and mating and subsequently exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment of inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC. These alterations of pERK occurred in CaMKII-expressing neurons, suggesting changes in efferent projections of these areas. Altogether, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.

  7. The role of visual cortex acetylcholine in learning to discriminate temporally modulated visual stimuli

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    Victor H Minces

    2013-03-01

    Full Text Available Cholinergic neurons in the basal forebrain innervate discrete regions of the cortical mantle, bestowing the cholinergic system with the potential to dynamically modulate sub-regions of the cortex according to behavioral demands. Cortical cholinergic activity has been shown to facilitate learning and modulate attention. Experiments addressing these issues have primarily focused on widespread cholinergic depletions, extending to areas involved in general cognitive processes and sleep cycle regulation, making a definitive interpretation of the behavioral role of cholinergic projections difficult. Furthermore, a review of the electrophysiological literature suggests that cholinergic modulation is particularly important in representing the fine temporal details of stimuli, an issue rarely addressed in behavioral experimentation. The goal of this work is to understand the role cholinergic projections, specific to the sensory cortex, in learning to discriminate fine differences in the temporal structure of stimuli. A novel visual Go/No-Go task was developed to assess the ability of rats to learn and discriminate fine differences in the temporal structure of visual stimuli (lights flashing at various frequencies. The cholinergic contribution to this task was examined by selectively eliminating acetylcholine projections to visual cortex (using 192 IgG-saporin, either before or after discrimination training.We find that in the face of compromised cholinergic input to the visual cortex, the rats’ ability to learn to perform fine discriminations is impaired, whereas their ability to perform discriminations remains unaffected.These results suggest that acetylcholine serves the role of facilitating plastic changes in the sensory cortices that are needed for an animal to refine their sensitivity to the temporal characteristics of relevant stimuli.

  8. The role of hearing ability and speech distortion in the facilitation of articulatory motor cortex.

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    Nuttall, Helen E; Kennedy-Higgins, Daniel; Devlin, Joseph T; Adank, Patti

    2017-01-08

    Excitability of articulatory motor cortex is facilitated when listening to speech in challenging conditions. Beyond this, however, we have little knowledge of what listener-specific and speech-specific factors engage articulatory facilitation during speech perception. For example, it is unknown whether speech motor activity is independent or dependent on the form of distortion in the speech signal. It is also unknown if speech motor facilitation is moderated by hearing ability. We investigated these questions in two experiments. We applied transcranial magnetic stimulation (TMS) to the lip area of primary motor cortex (M1) in young, normally hearing participants to test if lip M1 is sensitive to the quality (Experiment 1) or quantity (Experiment 2) of distortion in the speech signal, and if lip M1 facilitation relates to the hearing ability of the listener. Experiment 1 found that lip motor evoked potentials (MEPs) were larger during perception of motor-distorted speech that had been produced using a tongue depressor, and during perception of speech presented in background noise, relative to natural speech in quiet. Experiment 2 did not find evidence of motor system facilitation when speech was presented in noise at signal-to-noise ratios where speech intelligibility was at 50% or 75%, which were significantly less severe noise levels than used in Experiment 1. However, there was a significant interaction between noise condition and hearing ability, which indicated that when speech stimuli were correctly classified at 50%, speech motor facilitation was observed in individuals with better hearing, whereas individuals with relatively worse but still normal hearing showed more activation during perception of clear speech. These findings indicate that the motor system may be sensitive to the quantity, but not quality, of degradation in the speech signal. Data support the notion that motor cortex complements auditory cortex during speech perception, and point to a role

  9. Investigation of neural correlates between perception of pain and hemodynamic response measured in the pre-frontal cortex using functional near infra-red spectroscopy

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    Krishnamurthy, Venkatagiri

    Perception of pain is multi-dimensional, comprising three major psychological dimensions: sensory-discriminative, motivational-affective and cognitive-evaluative. This dissertation study investigates the cognitive evaluation of pain, by acquiring functional Near Infra-Red Spectroscopic (fNIRS) measurements from the prefrontal cortex (PFC) areas, during mechanical and thermal pain stimulation induced on the subject's volar forearm. Clustered-wise analysis on the oxy-hemoglobin (HbO) response from specific PFC areas was followed by categorizing the resulting HbO response into early (0.1--12sec) and late (12.1--25sec) phases. For each respective phase, regression analysis was carried between the HbO-derived parameters and behaviorally measured pain rating. The major findings of this study include: (1) across both 41°C and 48°C thermal stimulation, significant DeltaHbO deactivation was observed during the late phase, in the left hemispheric (LH) anterior PFC (aPFC) or Brodmann area 10 (BA 10). (2) Significant correlates of pain rating were observed in the LH prefrontal areas: (a) under mechanical stimulation, early phase HbO-derived peak intensity (PI) from LH aPFC correlated with the pain rating. (b) Under both 41°C and 48°C thermal stimulation, late phase HbO-derived PI from the LH dorsolateral PFC (DLPFC or BA 46) showed correlation with the pain rating. (3) The significant correlates observed from the right hemispheric (RH) PFC were: (a) under mechanical stimulation, early phase HbO-derived FWHM from the RH aPFC correlated with the pain rating. (b) Under 41°C thermal stimulation, late phase HbO-derived PI from the RH DLPFC area correlated with the pain rating. (4) The late phase HbO-derived time to peak from LH aPFC reflected cognitive discrimination of two different pain levels (41°C and 48°C). The observed trend for DeltaHbO activation and deactivation could possibly be due to synaptic-induced vasodilation and vasoconstriction leading to increased or

  10. Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes.

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    Tanahashi, Shunske; Yamamura, Satoshi; Nakagawa, Masanori; Motomura, Eishi; Okada, Motohiro

    2012-03-01

    Deficient transmission at the glutamate NMDA receptor is considered a key component of the pathophysiology of schizophrenia. However, the effects of antipsychotic drugs on the release of the endogenous NMDA receptor partial agonist, D-serine, remain to be clarified. We determined the interaction between antipsychotic drugs (clozapine and haloperidol) and transmission-modulating toxins (tetanus toxin, fluorocitrate, tetrodotoxin) on the release of L-glutamate and D-serine in the medial prefrontal cortex (mPFC) of freely moving rats, using microdialysis, and primary cultures of astrocytes using extreme high-pressure liquid chromatography. Release of L-glutamate and D-serine in the mPFC and in cultured astrocytes was inhibited by tetanus toxin (a synaptobrevin inhibitor) and fluorocitrate (a glial toxin), whereas tetrodotoxin (a voltage-sensitive Na(+) blocker) inhibited depolarization-induced L-glutamate release in the mPFC without affecting that of D-serine. Clozapine (1 and 5 mg·kg(-1)), but not haloperidol (0.5 and 1 mg·kg(-1)), dose-dependently increased L-glutamate and D-serine release from both astrocytes and mPFC. Clozapine-induced release of L-glutamate and D-serine was also reduced by tetanus toxin and fluorocitrate. Tetrodotoxin reduced clozapine-induced mPFC L-glutamate release but not that of D-serine. Clozapine-induced L-glutamate release preceded clozapine-induced D-serine release. MK-801 (a NMDA receptor antagonist) inhibited the delayed clozapine-induced L-glutamate release without affecting that of D-serine. Clozapine predominantly activated glial exocytosis of D-serine, and this clozapine-induced D-serine release subsequently enhances neuronal L-glutamate release via NMDA receptor activation. The enhanced D-serine associated glial transmission seems a novel mechanism of action of clozapine but not haloperidol. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  11. Mental reversal of imagined melodies: a role for the posterior parietal cortex.

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    Zatorre, Robert J; Halpern, Andrea R; Bouffard, Marc

    2010-04-01

    Two fMRI experiments explored the neural substrates of a musical imagery task that required manipulation of the imagined sounds: temporal reversal of a melody. Musicians were presented with the first few notes of a familiar tune (Experiment 1) or its title (Experiment 2), followed by a string of notes that was either an exact or an inexact reversal. The task was to judge whether the second string was correct or not by mentally reversing all its notes, thus requiring both maintenance and manipulation of the represented string. Both experiments showed considerable activation of the superior parietal lobe (intraparietal sulcus) during the reversal process. Ventrolateral and dorsolateral frontal cortices were also activated, consistent with the memory load required during the task. We also found weaker evidence for some activation of right auditory cortex in both studies, congruent with results from previous simpler music imagery tasks. We interpret these results in the context of other mental transformation tasks, such as mental rotation in the visual domain, which are known to recruit the intraparietal sulcus region, and we propose that this region subserves general computations that require transformations of a sensory input. Mental imagery tasks may thus have both task or modality-specific components as well as components that supersede any specific codes and instead represent amodal mental manipulation.

  12. Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI neurons of prefrontal cortex.

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    Proulx, Eliane; Piva, Matthew; Tian, Michael K; Bailey, Craig D C; Lambe, Evelyn K

    2014-04-01

    Cholinergic modulation of prefrontal cortex is essential for attention. In essence, it focuses the mind on relevant, transient stimuli in support of goal-directed behavior. The excitation of prefrontal layer VI neurons through nicotinic acetylcholine receptors optimizes local and top-down control of attention. Layer VI of prefrontal cortex is the origin of a dense feedback projection to the thalamus and is one of only a handful of brain regions that express the α5 nicotinic receptor subunit, encoded by the gene chrna5. This accessory nicotinic receptor subunit alters the properties of high-affinity nicotinic receptors in layer VI pyramidal neurons in both development and adulthood. Studies investigating the consequences of genetic deletion of α5, as well as other disruptions to nicotinic receptors, find attention deficits together with altered cholinergic excitation of layer VI neurons and aberrant neuronal morphology. Nicotinic receptors in prefrontal layer VI neurons play an essential role in focusing attention under challenging circumstances. In this regard, they do not act in isolation, but rather in concert with cholinergic receptors in other parts of prefrontal circuitry. This review urges an intensification of focus on the cellular mechanisms and plasticity of prefrontal attention circuitry. Disruptions in attention are one of the greatest contributing factors to disease burden in psychiatric and neurological disorders, and enhancing attention may require different approaches in the normal and disordered prefrontal cortex.

  13. Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex.

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    Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C H

    2017-07-01

    The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs.

  14. Vestibular-related frontal cortical areas and their roles in smooth-pursuit eye movements: representation of neck velocity, neck-vestibular interactions and memory-based smooth-pursuit

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    Kikuro eFukushima

    2011-12-01

    Full Text Available Smooth-pursuit eye movements are voluntary responses to small slow-moving objects in the fronto-parallel plane. They evolved in primates, who possess high-acuity foveae, to ensure clear vision about the moving target. The primate frontal cortex contains two smooth-pursuit related areas; the caudal part of the frontal eye fields (FEF and the supplementary eye fields (SEF. Both areas receive vestibular inputs. We review functional differences between the two areas in smooth-pursuit. Most FEF pursuit neurons signal pursuit parameters such as eye velocity and gaze-velocity, and are involved in cancelling the vestibulo-ocular reflex by linear addition of vestibular and smooth-pursuit responses. In contrast, gaze-velocity signals are rarely represented in the SEF. Most FEF pursuit neurons receive neck velocity inputs, while discharge modulation during pursuit and trunk-on-head rotation adds linearly. Linear addition also occurs between neck velocity responses and vestibular responses during head-on-trunk rotation in a task-dependent manner. During cross-axis pursuit-vestibular interactions, vestibular signals effectively initiate predictive pursuit eye movements. Most FEF pursuit neurons discharge during the interaction training after the onset of pursuit eye velocity, making their involvement unlikely in the initial stages of generating predictive pursuit. Comparison of representative signals in the two areas and the results of chemical inactivation during a memory-based smooth-pursuit task indicate they have different roles; the SEF plans smooth-pursuit including working memory of motion-direction, whereas the caudal FEF generates motor commands for pursuit eye movements. Patients with idiopathic Parkinson’s disease were asked to perform this task, since impaired smooth-pursuit and visual working memory deficit during cognitive tasks have been reported in most patients. Preliminary results suggested specific roles of the basal ganglia in memory

  15. Examining cognitive emotion regulation in frontal lobe patients: The mediating role of response inhibition.

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    Falquez, Rosalux; Dinu-Biringer, Ramona; Stopsack, Malte; Arens, Elisabeth A; Wick, Wolfgang; Barnow, Sven

    2015-01-01

    Previous investigations have demonstrated the relationship between inhibitory deficits and maladaptive emotion regulation. Although several neuropsychological studies show that frontal lobe damage can lead to extreme inhibition impairments, there have been no investigations regarding the influence of frontal lobe damage and related inhibition impairments on the use of maladaptive strategies. The goal of the current study was to examine the impact of executive functions impairments due to frontal lobe damage on cognitive emotion regulation. Fifteen patients with frontal lobe damage were compared to twenty-two healthy controls on their reported use of maladaptive strategies. The effect of behavioral inhibition deficits among the frontal lobe damage group was examined. Patients reflected a heightened use of maladaptive strategies compared to healthy controls, significantly mediated by Go/NoGo task errors, which are an indicator for response inhibition deficits. Results suggest that a heightened use of maladaptive strategies by patients relies to a strong extent on their impaired impulse control, highlighting the complex interplay between executive functions and emotional regulation.

  16. A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat.

    Science.gov (United States)

    Hussein, Ahmed M; Aher, Yogesh D; Kalaba, Predrag; Aher, Nilima Y; Dragačević, Vladimir; Radoman, Bojana; Ilić, Marija; Leban, Johann; Beryozkina, Tetyana; Ahmed, Abdel Baset M A; Urban, Ernst; Langer, Thierry; Lubec, Gert

    2017-08-14

    A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat. CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system. The working memory index (WMI) was evaluated in male Sprague Dawley rats that were intraperitoneally injected with CE-125 (1 or 10mg/kg body weight). In order to evaluate basic neurotoxicity, the open field, elevated plus maze, rota rod studies and the forced swim test were carried out. Frontal cortex was taken at the last day of the RAM test and dopamine receptors D1R and D2R, DAT and phosphorylated DAT protein levels were determined. On the 10th day both doses were increasing the WMI as compared to the vehicle-treated group. In both, trained and treated groups, D1R levels were significantly reduced while D2R levels were unchanged. DAT levels were comparable between all groups while phosphorylated DAT levels were increased in the trained group treated with 1mg/kg body weight. CE-125 as a probably non-neurotoxic compound and specific reuptake inhibitor was shown to increase performance (WMI) and modulation of the dopaminergic system is proposed as a possible mechanism of action. Copyright © 2017. Published by Elsevier B.V.

  17. Development of abstract thinking during childhood and adolescence: The role of rostrolateral prefrontal cortex

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    Iroise Dumontheil

    2014-10-01

    Full Text Available Rostral prefrontal cortex (RPFC has increased in size and changed in terms of its cellular organisation during primate evolution. In parallel emerged the ability to detach oneself from the immediate environment to process abstract thoughts and solve problems and to understand other individuals’ thoughts and intentions. Rostrolateral prefrontal cortex (RLPFC is thought to play an important role in supporting the integration of abstract, often self-generated, thoughts. Thoughts can be temporally abstract and relate to long term goals, or past or future events, or relationally abstract and focus on the relationships between representations rather than simple stimulus features. Behavioural studies have provided evidence of a prolonged development of the cognitive functions associated with RLPFC, in particular logical and relational reasoning, but also episodic memory retrieval and prospective memory. Functional and structural neuroimaging studies provide further support for a prolonged development of RLPFC during adolescence, with some evidence of increased specialisation of RLPFC activation for relational integration and aspects of episodic memory retrieval. Topics for future research will be discussed, such as the role of medial RPFC in processing abstract thoughts in the social domain, the possibility of training abstract thinking in the domain of reasoning, and links to education.

  18. Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition

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    Adam M P Miller

    2014-08-01

    Full Text Available Spatial navigation requires representations of landmarks and other navigation cues. The retrosplenial cortex (RSC is anatomically positioned between limbic areas important for memory formation, such as the hippocampus and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the hippocampus. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the hippocampus and as a target of the hippocampal-dependent systems consolidation of long-term memory.

  19. Automated MRI parcellation of the frontal lobe.

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    Ranta, Marin E; Chen, Min; Crocetti, Deana; Prince, Jerry L; Subramaniam, Krish; Fischl, Bruce; Kaufmann, Walter E; Mostofsky, Stewart H

    2014-05-01

    Examination of associations between specific disorders and physical properties of functionally relevant frontal lobe sub-regions is a fundamental goal in neuropsychiatry. Here, we present and evaluate automated methods of frontal lobe parcellation with the programs FreeSurfer(FS) and TOADS-CRUISE(T-C), based on the manual method described in Ranta et al. [2009]: Psychiatry Res 172:147-154 in which sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: i.e., primary motor cortex, anterior cingulate, deep white matter, premotor cortex regions (supplementary motor complex, frontal eye field, and lateral premotor cortex) and prefrontal cortex (PFC) regions (medial PFC, dorsolateral PFC, inferior PFC, lateral orbitofrontal cortex [OFC] and medial OFC). Dice's coefficient, a measure of overlap, and percent volume difference were used to measure the reliability between manual and automated delineations for each frontal lobe region. For FS, mean Dice's coefficient for all regions was 0.75 and percent volume difference was 21.2%. For T-C the mean Dice's coefficient was 0.77 and the mean percent volume difference for all regions was 20.2%. These results, along with a high degree of agreement between the two automated methods (mean Dice's coefficient = 0.81, percent volume difference = 12.4%) and a proof-of-principle group difference analysis that highlights the consistency and sensitivity of the automated methods, indicate that the automated methods are valid techniques for parcellation of the frontal lobe into functionally relevant sub-regions. Thus, the methodology has the potential to increase efficiency, statistical power and reproducibility for population analyses of neuropsychiatric disorders with hypothesized frontal lobe contributions. Copyright © 2013 Wiley Periodicals, Inc.

  20. Role of the right inferior parietal cortex in auditory selective attention: An rTMS study.

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    Bareham, Corinne A; Georgieva, Stanimira D; Kamke, Marc R; Lloyd, David; Bekinschtein, Tristan A; Mattingley, Jason B

    2018-02-01

    Selective attention is the process of directing limited capacity resources to behaviourally relevant stimuli while ignoring competing stimuli that are currently irrelevant. Studies in healthy human participants and in individuals with focal brain lesions have suggested that the right parietal cortex is crucial for resolving competition for attention. Following right-hemisphere damage, for example, patients may have difficulty reporting a brief, left-sided stimulus if it occurs with a competitor on the right, even though the same left stimulus is reported normally when it occurs alone. Such "extinction" of contralesional stimuli has been documented for all the major sense modalities, but it remains unclear whether its occurrence reflects involvement of one or more specific subregions of the temporo-parietal cortex. Here we employed repetitive transcranial magnetic stimulation (rTMS) over the right hemisphere to examine the effect of disruption of two candidate regions - the supramarginal gyrus (SMG) and the superior temporal gyrus (STG) - on auditory selective attention. Eighteen neurologically normal, right-handed participants performed an auditory task, in which they had to detect target digits presented within simultaneous dichotic streams of spoken distractor letters in the left and right channels, both before and after 20 min of 1 Hz rTMS over the SMG, STG or a somatosensory control site (S1). Across blocks, participants were asked to report on auditory streams in the left, right, or both channels, which yielded focused and divided attention conditions. Performance was unchanged for the two focused attention conditions, regardless of stimulation site, but was selectively impaired for contralateral left-sided targets in the divided attention condition following stimulation of the right SMG, but not the STG or S1. Our findings suggest a causal role for the right inferior parietal cortex in auditory selective attention. Copyright © 2017 Elsevier Ltd. All rights

  1. A role for primate subgenual cingulate cortex in sustaining autonomic arousal.

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    Rudebeck, Peter H; Putnam, Philip T; Daniels, Teresa E; Yang, Tianming; Mitz, Andrew R; Rhodes, Sarah E V; Murray, Elisabeth A

    2014-04-08

    The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience.

  2. The Emerging Neurobiology of Attention Deficit Hyperactivity Disorder: The Key Role of the Prefrontal Association Cortex

    Science.gov (United States)

    Arnsten, Amy F.T.

    2009-01-01

    Attention deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention, impulsivity, and locomotor hyperactivity. Recent advances in neurobiology, imaging, and genetics have led to a greater understanding of the etiology and treatment of ADHD. Studies have found that ADHD is associated with weaker function and structure of prefrontal cortex (PFC) circuits, especially in the right hemisphere. The prefrontal association cortex plays a crucial role in regulating attention, behavior, and emotion, with the right hemisphere specialized for behavioral inhibition. The PFC is highly dependent on the correct neurochemical environment for proper function: noradrenergic stimulation of postsynaptic alpha-2A adrenoceptors and dopaminergic stimulation of D1 receptors is necessary for optimal prefrontal function. ADHD is associated with genetic changes that weaken catecholamine signaling and, in some patients, with slowed PFC maturation. Effective pharmacologic treatments for ADHD all enhance catecholamine signaling in the PFC and strengthen its regulation of attention and behavior. Recent animal studies show that therapeutic doses of stimulant medications preferentially increase norepinephrine and, to a lesser extent, dopamine, in the PFC. These doses reduce locomotor activity and improve PFC regulation of attention and behavior through enhanced catecholamine stimulation of alpha-2A and D1 receptors. These findings in animals are consistent with improved PFC function in normal human subjects and, more prominently, in patients with ADHD. Thus, a highly cohesive story is emerging regarding the etiology and treatment of ADHD. PMID:20596295

  3. Role of the human retrosplenial cortex/parieto-occipital sulcus in perspective priming.

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    Sulpizio, Valentina; Committeri, Giorgia; Lambrey, Simon; Berthoz, Alain; Galati, Gaspare

    2016-01-15

    The ability to imagine the world from a different viewpoint is a fundamental competence for spatial reorientation and for imagining what another individual sees in the environment. Here, we investigated the neural bases of such an ability using functional magnetic resonance imaging. Healthy participants detected target displacements across consecutive views of a familiar virtual room, either from the perspective of an avatar (primed condition) or in the absence of such a prime (unprimed condition). In the primed condition, the perspective at test always corresponded to the avatar's perspective, while in the unprimed condition it was randomly chosen as 0, 45 or 135deg of viewpoint rotation. We observed a behavioral advantage in performing a perspective transformation during the primed condition as compared to an equivalent amount of unprimed perspective change. Although many cortical regions (dorsal parietal, parieto-temporo-occipital junction, precuneus and retrosplenial cortex/parieto-occipital sulcus or RSC/POS) were involved in encoding and retrieving target location from different perspectives and were modulated by the amount of viewpoint rotation, the RSC/POS was the only area showing decreased activity in the primed as compared to the unprimed condition, suggesting that this region anticipates the upcoming perspective change. The retrosplenial cortex/parieto-occipital sulcus appears to play a special role in the allocentric coding of heading directions. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Stroop interference and AQT cognitive speed may play complementary roles in differentiating dementias with frontal and posterior lesions.

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    Fleck, Christy; Wiig, Elisabeth H; Corwin, Melinda

    2015-04-01

    Forty neurotypical adults (ages 65-74) were administered three different assessments, as follows: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive Speed (AQT), and Stroop Color and Word Test. Correlation coefficients (Pearson r) indicated a significant but moderate association between MoCA scores and AQT dual-dimension processing speed (p Stroop Color, Word, and Color-Word t-scores, and the observed statistical power was high. Form naming correlated significantly with Stroop Word and Color-Word measures (p Stroop interference measures were low and non-significant (p > 0.01). Based on evidence of frontal lobe control of inhibition (Stroop) and bilateral temporal-parietal control of dual-dimension processing speed (AQT), results suggest that the AQT dual-dimension processing-speed and Stroop interference tests may complement each other in differentiating dementias associated with frontal and posterior lesions.

  5. Frontal Connectivity in EEG Gamma (30-45 Hz) Respond to Spinal Cord Stimulation in Minimally Conscious State Patients.

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    Bai, Yang; Xia, Xiaoyu; Liang, Zhenhu; Wang, Yong; Yang, Yi; He, Jianghong; Li, Xiaoli

    2017-01-01

    Spinal cord stimulation (SCS) has become a valuable brain-intervention technique used to rehabilitate patients with disorders of consciousness (DOC). To explore how the SCS affects the cerebral cortex and what possible electrophysiological mechanism of SCS effects on the cortex, the present study investigated the functional connectivity and network properties during SCS in minimally conscious state (MCS) patients. MCS patients received both SCS and sham sessions. Functional connectivity of the phase lock value (PLV) in the gamma band (30-45 Hz) was investigated at the pre-, on- and post-SCS stages. In addition, to evaluate global network properties, complex network parameters, including average path length, cluster coefficient and small-world, were measured. When SCS was turned on, significantly decreased connectivity was noted in the local scale of the frontal-frontal region and in the large scales of the frontal-parietal and frontal-occipital regions. The global network showed fewer small-world properties, average path lengths increased and cluster coefficients decreased. When SCS was turned off, the large-scale connectivity and global network returned to its pre-SCS level, but the local scale of frontal-frontal connectivity remained significantly lower than its pre-SCS level. Sham sessions produced no significant changes in either functional connectivity or network. The findings directly showed that SCS could effectively intervene cortical gamma activity, and the intervention included immediate global effects (large scale connectivity and network alteration only occurred in stimulation period) and long-lasting local effects (local scale connectivity alteration persist beyond stimulation period). Moreover, considering the mechanism and propagation of gamma activity, it indicates that the frontal cortex plays a crucial role in the SCS effects on the cerebral cortex.

  6. Causal role of prefrontal cortex in the threshold for access to consciousness.

    Science.gov (United States)

    Del Cul, A; Dehaene, S; Reyes, P; Bravo, E; Slachevsky, A

    2009-09-01

    What neural mechanisms support our conscious perception of briefly presented stimuli? Some theories of conscious access postulate a key role of top-down amplification loops involving prefrontal cortex (PFC). To test this issue, we measured the visual backward masking threshold in patients with focal prefrontal lesions, using both objective and subjective measures while controlling for putative attention deficits. In all conditions of temporal or spatial attention cueing, the threshold for access to consciousness was systematically shifted in patients, particular after a lesion of the left anterior PFC. The deficit affected subjective reports more than objective performance, and objective performance conditioned on subjective visibility was essentially normal. We conclude that PFC makes a causal contribution to conscious visual perception of masked stimuli, and outline a dual-route signal detection theory of objective and subjective decision making.

  7. Role of mechanical factors in the morphology of the primate cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Claus C Hilgetag

    2006-03-01

    Full Text Available The convoluted cortex of primates is instantly recognizable in its principal morphologic features, yet puzzling in its complex finer structure. Various hypotheses have been proposed about the mechanisms of its formation. Based on the analysis of databases of quantitative architectonic and connection data for primate prefrontal cortices, we offer support for the hypothesis that tension exerted by corticocortical connections is a significant factor in shaping the cerebral cortical landscape. Moreover, forces generated by cortical folding influence laminar morphology, and appear to have a previously unsuspected impact on cellular migration during cortical development. The evidence for a significant role of mechanical factors in cortical morphology opens the possibility of constructing computational models of cortical development based on physical principles. Such models are particularly relevant for understanding the relationship of cortical morphology to the connectivity of normal brains, and structurally altered brains in diseases of developmental origin, such as schizophrenia and autism.

  8. Toward a theoretical role for tonic norepinephrine in the orbitofrontal cortex in facilitating flexible learning.

    Science.gov (United States)

    Sadacca, Brian F; Wikenheiser, Andrew M; Schoenbaum, Geoffrey

    2017-03-14

    To adaptively respond in a complex, changing world, animals need to flexibly update their understanding of the world when their expectations are violated. Though several brain regions in rodents and primates have been implicated in aspects of this updating, current models of orbitofrontal cortex (OFC) and norepinephrine neurons of the locus coeruleus (LC-NE) suggest that each plays a role in responding to environmental change, where the OFC allows updating of prior learning to occur without overwriting or unlearning one's previous understanding of the world that changed, while elevated tonic NE allows for increased flexibility in behavior that tracks an animal's uncertainty. In light of recent studies highlighting a specific LC-NE projection to the OFC, in this review we discuss current models of OFC and NE function, and their potential synergy in the updating of associations following environmental change. Published by Elsevier Ltd.

  9. Insights from Neuropsychology: Pinpointing the role of the Posterior Parietal Cortex in Episodic and Working Memory

    Directory of Open Access Journals (Sweden)

    Marian E. Berryhill

    2012-06-01

    Full Text Available The role of posterior parietal cortex (PPC in various forms of memory is a current topic of interest in the broader field of cognitive neuroscience. This large cortical region has been linked with a wide range of mnemonic functions affecting each stage of memory processing: encoding, maintenance and retrieval. Yet, the precise role of the PPC in memory remains mysterious and controversial. Progress in understanding PPC function will require researchers to incorporate findings in a convergent manner from multiple experimental techniques rather than emphasizing a particular type of data. To facilitate this process, here, we review findings from the human neuropsychological research and examine the consequences to memory following PPC damage. Recent patient-based research findings have investigated two typically disconnected fields: working memory and episodic memory. The findings from patient participants with unilateral and bilateral PPC lesions performing diverse experimental paradigms are summarized. These findings are then related to findings from other techniques including neurostimulation (TMS and tDCS and the influential and more abundant functional neuroimaging literature. We then review the strengths and weaknesses of hypotheses proposed to account for PPC function in these forms of memory. Finally, we address what missing evidence is needed to clarify the role(s of the PPC in memory.

  10. The role of orbitofrontal cortex in processing empathy stories in 4-8 year-old children

    Directory of Open Access Journals (Sweden)

    Tila Tabea eBrink

    2011-04-01

    Full Text Available This study investigates the neuronal correlates of empathic processing in childrenaged 4 to 8 years, an age range discussed to be crucial for the development ofempathy. Empathy, defined as the ability to understand and share another person’sinner life, consists of two components: affective (emotion-sharing and cognitiveempathy (Theory of Mind. We examined the hemodynamic responses of pre-schooland school children (N=48, while they processed verbal (auditory and non-verbal(cartoons empathy stories in a passive following paradigm, using functional NearInfrared Spectroscopy (fNIRS. To control for the two types of empathy, childrenwere presented blocks of stories eliciting either affective or cognitive empathy, orneutral scenes which relied on the understanding of physical causalities.By contrasting the activations of the younger and older children, we expected toobserve developmental changes in brain activations when children process storieseliciting empathy in either stimulus modality towards a greater involvement ofanterior frontal brain regions. Our results indicate that children's processing of storieseliciting affective and cognitive empathy is associated with medial and bilateralorbitofrontal cortex (OFC activation. In contrast to what is known from studies usingadult participants, no additional recruitment of posterior brain regions was observed,often associated with the processing of stories eliciting empathy. Developmentalchanges were found only for stories eliciting affective empathy with increasedactivation, in older children, in medial OFC, left inferior frontal gyrus (IFG, and theleft dorsolateral prefrontal cortex (dlPFC. Activations for the two modalities differonly little, with non-verbal presentation of the stimuli having a greater impact onempathy processing in children, showing more similarities to adult processing thanthe verbal one. This might be caused by the fact that non-verbal processing developsearlier in life

  11. The Role of Orbitofrontal Cortex in Processing Empathy Stories in 4- to 8-Year-Old Children

    Science.gov (United States)

    Brink, Tila Tabea; Urton, Karolina; Held, Dada; Kirilina, Evgeniya; Hofmann, Markus J.; Klann-Delius, Gisela; Jacobs, Arthur M.; Kuchinke, Lars

    2010-01-01

    This study investigates the neuronal correlates of empathic processing in children aged 4–8 years, an age range discussed to be crucial for the development of empathy. Empathy, defined as the ability to understand and share another person's inner life, consists of two components: affective (emotion-sharing) and cognitive empathy (Theory of Mind). We examined the hemodynamic responses of preschool and school children (N = 48), while they processed verbal (auditory) and non-verbal (cartoons) empathy stories in a passive following paradigm, using functional Near-Infrared Spectroscopy. To control for the two types of empathy, children were presented blocks of stories eliciting either affective or cognitive empathy, or neutral scenes which relied on the understanding of physical causalities. By contrasting the activations of the younger and older children, we expected to observe developmental changes in brain activations when children process stories eliciting empathy in either stimulus modality toward a greater involvement of anterior frontal brain regions. Our results indicate that children's processing of stories eliciting affective and cognitive empathy is associated with medial and bilateral orbitofrontal cortex (OFC) activation. In contrast to what is known from studies using adult participants, no additional recruitment of posterior brain regions was observed, often associated with the processing of stories eliciting empathy. Developmental changes were found only for stories eliciting affective empathy with increased activation, in older children, in medial OFC, left inferior frontal gyrus, and the left dorsolateral prefrontal cortex. Activations for the two modalities differ only little, with non-verbal presentation of the stimuli having a greater impact on empathy processing in children, showing more similarities to adult processing than the verbal one. This might be caused by the fact that non-verbal processing develops earlier in life and is more

  12. Functional Organization of the Parahippocampal Cortex: Dissociable Roles for Context Representations and the Perception of Visual Scenes.

    Science.gov (United States)

    Baumann, Oliver; Mattingley, Jason B

    2016-02-24

    The human parahippocampal cortex has been ascribed central roles in both visuospatial and mnemonic processes. More specifically, evidence suggests that the parahippocampal cortex subserves both the perceptual analysis of scene layouts as well as the retrieval of associative contextual memories. It remains unclear, however, whether these two functional roles can be dissociated within the parahippocampal cortex anatomically. Here, we provide evidence for a dissociation between neural activation patterns associated with visuospatial analysis of scenes and contextual mnemonic processing along the parahippocampal longitudinal axis. We used fMRI to measure parahippocampal responses while participants engaged in a task that required them to judge the contextual relatedness of scene and object pairs, which were presented either as words or pictures. Results from combined factorial and conjunction analyses indicated that the posterior section of parahippocampal cortex is driven predominantly by judgments associated with pictorial scene analysis, whereas its anterior section is more active during contextual judgments regardless of stimulus category (scenes vs objects) or modality (word vs picture). Activation maxima associated with visuospatial and mnemonic processes were spatially segregated, providing support for the existence of functionally distinct subregions along the parahippocampal longitudinal axis and suggesting that, in humans, the parahippocampal cortex serves as a functional interface between perception and memory systems. Copyright © 2016 the authors 0270-6474/16/362536-07$15.00/0.

  13. Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats.

    Science.gov (United States)

    Arguello, Amy A; Wang, Rong; Lyons, Carey M; Higginbotham, Jessica A; Hodges, Matthew A; Fuchs, Rita A

    2017-08-01

    Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation. Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol (BM)) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e., non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in experiment 2 received vehicle or BM into the AI after a 15-min reexposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later. BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine memory reconsolidation. These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.

  14. Understanding the role of the primary somatosensory cortex: Opportunities for rehabilitation.

    Science.gov (United States)

    Borich, M R; Brodie, S M; Gray, W A; Ionta, S; Boyd, L A

    2015-12-01

    Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Frontal alpha asymmetry predicts inhibitory processing in youth with attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Ellis, Alissa J; Kinzel, Chantelle; Salgari, Giulia C; Loo, Sandra K

    2017-07-28

    Atypical asymmetry in brain activity has been implicated in the behavioral and attentional dysregulation observed in ADHD. Specifically, asymmetry in neural activity in the right versus left frontal regions has been linked to ADHD, as well as to symptoms often associated with ADHD such as heightened approach behaviors, impulsivity and difficulties with inhibition. Clarifying the role of frontal asymmetry in ADHD-like traits, such as disinhibition, may provide information on the neurophysiological processes underlying these behaviors. ADHD youth (ADHD: n = 25) and healthy, typically developing controls (TD: n = 25) underwent an electroencephalography (EEG) recording while completing a go/no-go task-a commonly used test measuring behavioral inhibition. In addition, advanced signal processing for source localization estimated the location of signal generators underlying frontal alpha asymmetry (FA) during correct and incorrect trials. This is the first study in ADHD to demonstrate that the dorsal-lateral prefrontal cortex (DLPFC) may be responsible for generating frontal alpha. During failed inhibition trials, ADHD youth displayed greater FA than TD youth. In addition, within the ADHD group, frontal asymmetry during later processing stages (i.e., 400-800ms after stimulus) predicted a higher number of commission errors throughout the task. These results suggest that frontal alpha asymmetry may be a specific biomarker of cognitive disinhibition among youth with ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A radial glia-specific role of RhoA in double cortex formation

    DEFF Research Database (Denmark)

    Cappello, Silvia; Böhringer, Christian R J; Bergami, Matteo

    2012-01-01

    The positioning of neurons in the cerebral cortex is of crucial importance for its function as highlighted by the severe consequences of migrational disorders in patients. Here we show that genetic deletion of the small GTPase RhoA in the developing cerebral cortex results in two migrational...... disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex......, whereas the converse was not the case. Alterations in the radial glia scaffold are demonstrated to cause these migrational defects through destabilization of both the actin and the microtubules cytoskeleton. These data not only demonstrate that RhoA is largely dispensable for migration in neurons but also...

  17. Investigating the role of the ventromedial prefrontal cortex (vmPFC in the assessment of brands

    Directory of Open Access Journals (Sweden)

    Jose Paulo eSantos

    2011-06-01

    Full Text Available The ventromedial prefrontal cortex (vmPFC is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI study where 18 subjects assessed positive, indifferent and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  18. The Role of the Ventromedial Prefrontal Cortex in Purchase Intent Among Older Adults.

    Science.gov (United States)

    Koestner, Bryan P; Hedgcock, William; Halfmann, Kameko; Denburg, Natalie L

    2016-01-01

    Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex (vmPFC) may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging (fMRI). Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task (IGT). While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission (FTC). We then obtained behavioral measures involving comprehension of claims and purchase intention of the product in each advertisement. Contrasts show brain activity in the vmPFC was less correlated with purchase intention in impaired vs. unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

  19. Investigating the role of the ventromedial prefrontal cortex in the assessment of brands.

    Science.gov (United States)

    Santos, José Paulo; Seixas, Daniela; Brandão, Sofia; Moutinho, Luiz

    2011-01-01

    The ventromedial prefrontal cortex (vmPFC) is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI) study where 18 subjects assessed positive, indifferent, and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  20. Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

    Science.gov (United States)

    Castillo Saavedra, Laura; Mendonca, Mariana; Fregni, Felipe

    2014-09-01

    Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Role of the sensorimotor cortex in Tourette syndrome using multimodal imaging.

    Science.gov (United States)

    Tinaz, Sule; Belluscio, Beth A; Malone, Patrick; van der Veen, Jan Willem; Hallett, Mark; Horovitz, Silvina G

    2014-12-01

    Tourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Most patients describe uncomfortable premonitory sensations preceding the tics and a subjective experience of increased sensitivity to tactile stimuli. These reports indicate that a sensory processing disturbance is an important component of TS together with motor phenomena. Thus, we focused our investigation on the role of the sensorimotor cortex (SMC) in TS using multimodal neuroimaging techniques. We measured the gamma-aminobutyric acid (GABA)+/Creatine (Cre) ratio in the SMC using GABA (1) H magnetic resonance spectroscopy. We recorded the baseline beta activity in the SMC using magnetoencephalography and correlated GABA+/Cre ratio with baseline beta band power. Finally, we examined the resting state functional connectivity (FC) pattern of the SMC using functional magnetic resonance imaging (fMRI). GABA+/Cre ratio in the SMC did not differ between patients and controls. Correlation between the baseline beta band power and GABA+/Cre ratio was abnormal in patients. The anterior insula showed increased FC with the SMC in patients. These findings suggest that altered limbic input to the SMC and abnormal GABA-mediated beta oscillations in the SMC may underpin some of the sensorimotor processing disturbances in TS and contribute to tic generation. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  2. Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala.

    Science.gov (United States)

    Koenigs, Michael; Grafman, Jordan

    2009-10-01

    Posttraumatic stress disorder (PTSD) is characterized by recurrent distressing memories of an emotionally traumatic event. In this review, the authors present neuroscientific data highlighting the function of two brain areas--the amygdala and ventromedial prefrontal cortex (vmPFC)--in PTSD and related emotional processes. A convergent body of human and nonhuman studies suggests that the amygdala mediates the acquisition and expression of conditioned fear and the enhancement of emotional memory, whereas the vmPFC mediates the extinction of conditioned fear and the volitional regulation of negative emotion. It has been theorized that the vmPFC exerts inhibition on the amygdala, and that a defect in this inhibition could account for the symptoms of PTSD. This theory is supported by functional imaging studies of PTSD patients, who exhibit hypoactivity in the vmPFC but hyperactivity in the amygdala. A recent study of brain-injured and trauma-exposed combat veterans confirms that amygdala damage reduces the likelihood of developing PTSD. But contrary to the prediction of the top-down inhibition model, vmPFC damage also reduces the likelihood of developing PTSD. The putative roles of the amygdala and the vmPFC in the pathophysiology of PTSD, as well as implications for potential treatments, are discussed in light of these results.

  3. Perception of Upright: Multisensory Convergence and the Role of Temporo-Parietal Cortex

    Science.gov (United States)

    Kheradmand, Amir; Winnick, Ariel

    2017-01-01

    We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such “orientation constancy” is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i) neurobehavioral aspects of orientation constancy, (ii) sensory models that address the neurophysiology underlying perception of upright, and (iii) the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function. PMID:29118736

  4. Perception of Upright: Multisensory Convergence and the Role of Temporo-Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Amir Kheradmand

    2017-10-01

    Full Text Available We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such “orientation constancy” is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i neurobehavioral aspects of orientation constancy, (ii sensory models that address the neurophysiology underlying perception of upright, and (iii the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function.

  5. Role of orbitofrontal cortex neuronal ensembles in the expression of incubation of heroin craving

    Science.gov (United States)

    Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R.M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.

    2012-01-01

    In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin-seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6-h/d for 10 d) and assessed cue-induced heroin-seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin-seeking increased from 1 day to 14 days and was accompanied by increased Fos expression in ~12% of OFC neurons. Non-selective inactivation of OFC neurons with the GABA agonists baclofen+muscimol decreased cue-induced heroin-seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin-seeking after 14 withdrawal days. We trained cfos-lacZ transgenic rats to self-administer heroin and 11 days later re-exposed them to heroin-associated cues or novel cues for 15 min (induction day) followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 days later. Daun02 selectively decreased cue-induced heroin-seeking in rats previously re-exposed to the heroin-associated cues on induction day, but not in rats previously exposed to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving. PMID:22915104

  6. Attention and alcohol cues: a role for medial parietal cortex and shifting away from alcohol features?

    Directory of Open Access Journals (Sweden)

    Thomas Edward Gladwin

    2013-12-01

    Full Text Available Attention plays a central role in theories of alcohol dependence; however, its precise role in alcohol-related biases is not yet clear. In the current study, social drinkers performed a spatial cueing task designed to evoke conflict between automatic processes due to incentive salience and control exerted to follow task-related goals. Such conflict is a potentially important task feature from the perspective of dual-process models of addiction. Subjects received instructions either to direct their attention towards pictures of alcoholic beverages, and away from non-alcohol beverages; or to direct their attention towards pictures of non-alcoholic beverages, and away from alcohol beverages. A probe stimulus was likely to appear at the attended location, so that both spatial and non-spatial interference was possible. Activation in medial parietal cortex was found during Approach Alcohol versus Avoid Alcohol blocks. This region is associated with the, possibly automatic, shifting of attention between stimulus features, suggesting that subjects may have shifted attention away from certain features of alcoholic cues when attention had to be directed towards an upcoming stimulus at their location. Further, activation in voxels close to this region was negatively correlated with riskier drinking behavior. A tentative interpretation of the results is that risky drinking may be associated with a reduced tendency to shift attention away from potentially distracting task-irrelevant alcohol cues. The results suggest novel hypotheses and directions for future study, in particular towards the potential therapeutic use of training the ability to shifting attention away from alcohol-related stimulus features.

  7. A role for PDGF-C/PDGFRα signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex

    Directory of Open Access Journals (Sweden)

    Johanna Andrae

    2016-04-01

    Full Text Available Platelet-derived growth factor-C (PDGF-C is one of three known ligands for the tyrosine kinase receptor PDGFRα. Analysis of Pdgfc null mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFRα ligands might obscure additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants for Pdgfc−/− and PdgfraGFP/+. These mice display a range of severe phenotypes including spina bifida, lung emphysema, abnormal meninges and neuronal over-migration in the cerebral cortex. We focused our analysis on the central nervous system (CNS, where PDGF-C was identified as a critical factor for the formation of meninges and assembly of the glia limitans basement membrane. We also present expression data on Pdgfa, Pdgfc and Pdgfra in the cerebral cortex and microarray data on cerebral meninges.

  8. Cognitive Control of Episodic Memory in Schizophrenia: Differential Role of Dorsolateral and Ventrolateral Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    J Daniel eRagland

    2015-11-01

    Full Text Available Background. Dorsal (DLPFC and ventral (VLPFC subregions in lateral prefrontal cortex play distinct roles in episodic memory, and both are implicated in schizophrenia. We test the hypothesis that schizophrenia differentially impairs DLPFC versus VLPFC control of episodic encoding. Methods. Cognitive control was manipulated by requiring participants to encode targets and avoid encoding nontargets based upon stimulus properties of test stimuli (i.e., the match or miss-match of the color of the word and a surrounding frame. The more automatic encoding response (target versus nontarget was predicted to engage VLPFC in both groups. Conversely, having to overcome the prepotent encoding response (nontargets versus targets was predicted to produce greater DLPFC activation in controls than in patients. Encoding occurred during event-related fMRI in a sample of 21 individuals with schizophrenia and 30 healthy participants. Scanning was followed by recognition testing outside the scanner. Results. Patients were less successful differentially remembering target versus non-target stimuli, and retrieval difficulties correlated with more severe disorganized symptoms. As predicted, the target versus nontarget contrast activated the VLPFC and correlated with retrieval success in both groups. Conversely, the nontarget versus target contrast produced greater DLPFC activation in controls than in patients, and DLPFC activation correlated with performance only in controls.Conclusions. Individuals with schizophrenia can successfully engage the VLPFC to provide control over semantic encoding of individual items, but are specifically impaired at engaging the DLPFC to provide control over rule-guided encoding decisions. This extends previous cognitive control models based on response selection tasks to the memory domain.

  9. Role of early visual cortex in trans-saccadic memory of object features.

    Science.gov (United States)

    Malik, Pankhuri; Dessing, Joost C; Crawford, J Douglas

    2015-08-01

    Early visual cortex (EVC) participates in visual feature memory and the updating of remembered locations across saccades, but its role in the trans-saccadic integration of object features is unknown. We hypothesized that if EVC is involved in updating object features relative to gaze, feature memory should be disrupted when saccades remap an object representation into a simultaneously perturbed EVC site. To test this, we applied transcranial magnetic stimulation (TMS) over functional magnetic resonance imaging-localized EVC clusters corresponding to the bottom left/right visual quadrants (VQs). During experiments, these VQs were probed psychophysically by briefly presenting a central object (Gabor patch) while subjects fixated gaze to the right or left (and above). After a short memory interval, participants were required to detect the relative change in orientation of a re-presented test object at the same spatial location. Participants either sustained fixation during the memory interval (fixation task) or made a horizontal saccade that either maintained or reversed the VQ of the object (saccade task). Three TMS pulses (coinciding with the pre-, peri-, and postsaccade intervals) were applied to the left or right EVC. This had no effect when (a) fixation was maintained, (b) saccades kept the object in the same VQ, or (c) the EVC quadrant corresponding to the first object was stimulated. However, as predicted, TMS reduced performance when saccades (especially larger saccades) crossed the remembered object location and brought it into the VQ corresponding to the TMS site. This suppression effect was statistically significant for leftward saccades and followed a weaker trend for rightward saccades. These causal results are consistent with the idea that EVC is involved in the gaze-centered updating of object features for trans-saccadic memory and perception.

  10. Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex

    Directory of Open Access Journals (Sweden)

    Marianne Anke Stephan

    2016-05-01

    Full Text Available The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group. For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group. Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

  11. Saccade-related activity in the prefrontal cortex: its role in eye movement control and cognitive functions

    Science.gov (United States)

    Funahashi, Shintaro

    2014-01-01

    Prefrontal neurons exhibit saccade-related activity and pre-saccadic memory-related activity often encodes the directions of forthcoming eye movements, in line with demonstrated prefrontal contribution to flexible control of voluntary eye movements. However, many prefrontal neurons exhibit post-saccadic activity that is initiated well after the initiation of eye movement. Although post-saccadic activity has been observed in the frontal eye field, this activity is thought to be a corollary discharge from oculomotor centers, because this activity shows no directional tuning and is observed whenever the monkeys perform eye movements regardless of goal-directed or not. However, prefrontal post-saccadic activities exhibit directional tunings similar as pre-saccadic activities and show context dependency, such that post-saccadic activity is observed only when monkeys perform goal-directed saccades. Context-dependency of prefrontal post-saccadic activity suggests that this activity is not a result of corollary signals from oculomotor centers, but contributes to other functions of the prefrontal cortex. One function might be the termination of memory-related activity after a behavioral response is done. This is supported by the observation that the termination of memory-related activity coincides with the initiation of post-saccadic activity in population analyses of prefrontal activities. The termination of memory-related activity at the end of the trial ensures that the subjects can prepare to receive new and updated information. Another function might be the monitoring of behavioral performance, since the termination of memory-related activity by post-saccadic activity could be associated with informing the correctness of the response and the termination of the trial. However, further studies are needed to examine the characteristics of saccade-related activities in the prefrontal cortex and their functions in eye movement control and a variety of cognitive functions

  12. A key role of the prefrontal cortex in the maintenance of chronic tinnitus: An fMRI study using a Stroop task.

    Science.gov (United States)

    Araneda, Rodrigo; Renier, Laurent; Dricot, Laurence; Decat, Monique; Ebner-Karestinos, Daniela; Deggouj, Naïma; De Volder, Anne G

    2018-01-01

    Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients. Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision. We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP. Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

  13. Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol

    Science.gov (United States)

    Costin, Blair N.; Wolen, Aaron R.; Fitting, Sylvia; Shelton, Keith L.; Miles, Michael F.

    2012-01-01

    Background Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol. Acute ethanol activates the HPA axis, causing release of adrenal glucocorticoid hormones. Our prior genomic studies suggest glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute ethanol administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute ethanol. Such work could be significant, given the predictive value for level of response to acute ethanol in the risk for alcoholism. Methods We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis or loss-of-righting reflex (LORR)) or repeated (sensitization) ethanol treatment. Whole genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to ethanol following ADX. Results ADX and RU-486 both impaired acute ethanol (2 g/kg) induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered initiation of ethanol sensitization (locomotor activation or jump counts), ethanol-induced anxiolysis or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high dose RU-486 pre-treatment blunted ethanol-induced Fkbp5 expression. Conclusions Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent

  14. A computational role for bistability and traveling waves in motor cortex

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    Stewart eHeitmann

    2012-09-01

    Full Text Available Adaptive changes in behavior require rapid changes in brain states yet the brain must also remain stable. We investigated two neural mechanisms for evoking rapid transitions between spatiotemporal synchronization patterns of beta oscillations (13--30Hz in motor cortex. Cortex was modeled as a sheet of neural oscillators that were spatially coupled using a center-surround connection topology. Manipulating the inhibitory surround was found to evoke reliable transitions between synchronous oscillation patterns and traveling waves. These transitions modulated the simulated local field potential in agreement with physiological observations in humans. Intermediate levels of surround inhibition were also found to produce bistable coupling topologies that supported both waves and synchrony. State-dependent perturbation between bistable states produced very rapid transitions but were less reliable. We surmise that motor cortex may thus employ state-dependent computation to achieve very rapid changes between bistable motor states when the demand for speed exceeds the demand for accuracy.

  15. Insight in psychotic disorder: relation with psychopathology and frontal lobe function.

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    Kumar, Atmesh; Sharma, Pranjal; Das, Shyamanta; Nath, Kamal; Talukdar, Uddip; Bhagabati, Dipesh

    2014-01-01

    Through conceptualising poor insight in psychotic disorders as a form of anosognosia, frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. The objective of this study was to compare the relation of insight in patients with psychotic illness to that of psychopathology and frontal lobe function. Forty patients with psychotic disorder were selected from those attending the Department of Psychiatry in a tertiary care teaching hospital. The evaluation of insight was carried out using the Schedule for Assessment of Insight (SAI), that of frontal lobe function by the Frontal Assessment Battery (FAB) and psychopathology by the Brief Psychiatric Rating Scale (BPRS). The correlation coefficients were determined. A negative correlation between SAI and BPRS scores means that the BPRS score is opposite to SAI scores. When the SAI total score was compared with the FAB total score, the correlation coefficient demonstrated a positive correlation. Better insight predicted lesser psychopathology and also that poor insight would exist with greater psychopathology. Better insight predicted a higher functional status of frontal lobes and prefrontal cortex in particular. Insight deficits in schizophrenia and other psychotic illnesses are multidimensional. Integration of different aetiological factors like biological, psychopathological, environmental ones and others are necessary for a better understanding of insight in psychosis. Copyright © 2013 S. Karger AG, Basel.

  16. The role of prefrontal cortex during postural control in Parkinsonian syndromes a functional near-infrared spectroscopy study.

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    Mahoney, Jeannette R; Holtzer, Roee; Izzetoglu, Meltem; Zemon, Vance; Verghese, Joe; Allali, Gilles

    2016-02-15

    Postural instability represents a main source of disability in Parkinsonian syndromes and its pathophysiology is poorly understood. Indirect probes (i.e., mental imagery) of brain involvement support the role of prefrontal cortex as a key cortical region for postural control in older adults with and without Parkinsonian syndromes. Using functional near infrared spectroscopy (fNIRs) as a direct online cortical probe, this study aimed to compare neural activation patterns in prefrontal cortex, postural stability, and their respective interactions, in (1) patients with Parkinsonian syndromes; (2) those with mild parkinsonian signs; (3) and healthy older adults. Among 269 non-demented older adults (76.41 ± 6.70 years, 56% women), 26 individuals presented with Parkinsonian syndromes (Unified Parkinson's disease rating scale (UPDRS): 11.08 ± 3.60), 117 had mild parkinsonian signs (UPDRS: 3.21 ± 2.49), and 126 individuals were included as a healthy control group. Participants were asked to stand upright and count silently for ten seconds while changes in oxygenated hemoglobin levels over prefrontal cortex were measured using fNIRs. We simultaneously evaluated postural stability with center of pressure velocity data recorded on an instrumented walkway. Compared to healthy controls and patients with mild parkinsonian signs, patients with Parkinsonian syndromes demonstrated significantly higher prefrontal oxygenation levels to maintain postural stability. The pattern of brain activation and postural control of participants with mild parkinsonian signs were similar to that of normal controls. These findings highlight the online role of the prefrontal cortex in postural control in patients with Parkinsonian syndromes and afford the opportunity to improve therapeutic options for postural instability. Copyright © 2016. Published by Elsevier B.V.

  17. Pre-Orthographic Character String Processing and Parietal Cortex: A Role for Visual Attention in Reading?

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    Lobier, Muriel; Peyrin, Carole; Le Bas, Jean-Francois; Valdois, Sylviane

    2012-01-01

    The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of…

  18. A Unifying Model of the Role of the Infralimbic Cortex in Extinction and Habits

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    Barker, Jacqueline M.; Taylor, Jane R.; Chandler, L. Judson

    2014-01-01

    The infralimbic prefrontal cortex (IL) has been shown to be critical for the regulation of flexible behavior, but its precise function remains unclear. This region has been shown to be critical for the acquisition, consolidation, and expression of extinction learning, leading many to hypothesize that IL suppresses behavior as part of a…

  19. The role of the primary visual cortex in higher level vision.

    NARCIS (Netherlands)

    Mumford, D.; Romero, R.; Lamme, V.A.F.; Lee, T.S.

    1998-01-01

    In the classical feed-forward, modular view of visual processing, the primary visual cortex (area V1) is a module that serves to extract local features such as edges and bars. Representation and recognition of objects are thought to be functions of higher extrastriate cortical areas. This paper

  20. The roles of superficial amygdala and auditory cortex in music-evoked fear and joy.

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    Koelsch, Stefan; Skouras, Stavros; Fritz, Thomas; Herrera, Perfecto; Bonhage, Corinna; Küssner, Mats B; Jacobs, Arthur M

    2013-11-01

    This study investigates neural correlates of music-evoked fear and joy with fMRI. Studies on neural correlates of music-evoked fear are scant, and there are only a few studies on neural correlates of joy in general. Eighteen individuals listened to excerpts of fear-evoking, joy-evoking, as well as neutral music and rated their own emotional state in terms of valence, arousal, fear, and joy. Results show that BOLD signal intensity increased during joy, and decreased during fear (compared to the neutral condition) in bilateral auditory cortex (AC) and bilateral superficial amygdala (SF). In the right primary somatosensory cortex (area 3b) BOLD signals increased during exposure to fear-evoking music. While emotion-specific activity in AC increased with increasing duration of each trial, SF responded phasically in the beginning of the stimulus, and then SF activity declined. Psychophysiological Interaction (PPI) analysis revealed extensive emotion-specific functional connectivity of AC with insula, cingulate cortex, as well as with visual, and parietal attentional structures. These findings show that the auditory cortex functions as a central hub of an affective-attentional network that is more extensive than previously believed. PPI analyses also showed functional connectivity of SF with AC during the joy condition, taken to reflect that SF is sensitive to social signals with positive valence. During fear music, SF showed functional connectivity with visual cortex and area 7 of the superior parietal lobule, taken to reflect increased visual alertness and an involuntary shift of attention during the perception of auditory signals of danger. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Cytoarchitecture, probability maps and functions of the human frontal pole.

    Science.gov (United States)

    Bludau, S; Eickhoff, S B; Mohlberg, H; Caspers, S; Laird, A R; Fox, P T; Schleicher, A; Zilles, K; Amunts, K

    2014-06-01

    The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities. Copyright © 2013 Elsevier Inc. All

  2. Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: the role of the infralimbic cortex in context generalisation.

    Directory of Open Access Journals (Sweden)

    Rachel eAshwell

    2014-02-01

    Full Text Available The prelimbic and infralimbic regions of the rat medial prefrontal cortex (mPFC are important components of the limbic cortico-striatal circuit, receiving converging projections from the hippocampus (HPC and amygdala. Mounting evidence points to these regions having opposing roles in the regulation of the expression of contextual fear and context-induced cocaine-seeking. To investigate this functional differentiation in motivated behaviour further, this study employed a novel radial maze task previously shown to be dependent on the integrity of the hippocampus and its functional connection to the nucleus accumbens shell, to investigate the effects of selective excitotoxic lesions of the PL and IL upon the spatial contextual control over reward learning. To this end, rats were trained to develop discriminative responding towards a reward-associated discrete cue presented in three out of six spatial locations (3 arms out of 6 radial maze arms, and to avoid the same discrete cue presented in the other 3 spatial locations. Once acquired, the reward contingencies of the spatial locations were reversed, such that responding to the cue presented in a previously rewarded location is no longer rewarded. Furthermore, the acquisition of spatial learning was probed separately using conditioned place preference and the monitoring of arm selection at the beginning of each training session. Lesions of the PL transiently attenuated the acquisition of the initial cue approach training and spatial learning, while leaving reversal learning intact. In contrast, IL lesions led to a significantly superior performance of spatial context-dependent discriminative cue approach and reversal learning, in the absence of a significant preference for the new reward-associated spatial locations. These results indicate that the PL and IL have functionally dissociative, and potentially opposite roles in the regulation of spatial contextual control over appetitive learning.

  3. Testing the Role of Dorsal Premotor Cortex in Auditory-Motor Association Learning Using Transcranical Magnetic Stimulation (TMS.

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    Carlotta Lega

    Full Text Available Interactions between the auditory and the motor systems are critical in music as well as in other domains, such as speech. The premotor cortex, specifically the dorsal premotor cortex (dPMC, seems to play a key role in auditory-motor integration, and in mapping the association between a sound and the movement used to produce it. In the present studies we tested the causal role of the dPMC in learning and applying auditory-motor associations using 1 Hz repetitive Transcranical Magnetic Stimulation (rTMS. In this paradigm, non-musicians learn a set of auditory-motor associations through melody training in two contexts: first when the sound to key-press mapping was in a conventional sequential order (low to high tones mapped onto keys from left to right, and then when it was in a novel scrambled order. Participant's ability to match the four pitches to four computer keys was tested before and after the training. In both experiments, the group that received 1 Hz rTMS over the dPMC showed no significant improvement on the pitch-matching task following training, whereas the control group (who received rTMS to visual cortex did. Moreover, in Experiment 2 where the pitch-key mapping was novel, rTMS over the dPMC also interfered with learning. These findings suggest that rTMS over dPMC disturbs the formation of auditory-motor associations, especially when the association is novel and must be learned rather explicitly. The present results contribute to a better understanding of the role of dPMC in auditory-motor integration, suggesting a critical role of dPMC in learning the link between an action and its associated sound.

  4. The role of the left ventrolateral prefrontal cortex in online sentence processing

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    Nazbanou Nozari

    2014-04-01

    Full Text Available Introduction: Patients with damage to the left ventrolateral prefrontal cortex (VLPFC are often not impaired in understanding simple sentences. It is, however, possible that the damage may cause subclinical effects. If VLPFC has a role in biasing competition towards what is relevant to the task, we would expect patients with VLPFC damage to be slower in using the relevant information and discarding the irrelevant information when they process sentences online. Methods: Nine patients, five with lesions limited to VLPFC, and four with lesions sparing VLPFC participated. The groups were matched in age, education, WAB-AQ and total lesion volume. Two experiments explored processing of online cues during sentence comprehension by tracking eye fixations in a Visual World paradigm with four pictures. Participants only listened to the sentences and looked at the pictures. Experiment 1 investigated how quickly cues can be used for target identification using a simple “She will [verb] the [target].” sentence structure. The verbs in the restrictive condition were compatible with only one of the four pictures (e.g., “eat”; target “apple” + three inedible competitors. The verbs in the control conditions were matched to the restrictive verbs in length and frequency, but did not point to a unique target (e.g., “see”. If VLPFC is critical for quickly biasing competition towards the relevant target, the VLPFC patients should to be slower than the non-VLPFC patients in fixating the noun when the verb is restrictive. Experiment 2 probed how effectively irrelevant cues are suppressed. A similar Visual World paradigm was used, but all verbs were restrictive, and one of the distractors was also compatible with the verb (e.g., “banana”. The sentences contained an adjective that ruled out one of verb-compatible pictures (e.g., “red”. The critical manipulation involved a third picture (the adjective competitor which was compatible with the

  5. Role of the prefrontal cortex in the cognitive control of reaching movements: near-infrared spectroscopy study

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    Goto, Kotaro; Hoshi, Yoko; Sata, Masashi; Kawahara, Masatoshi; Takahashi, Makoto; Murohashi, Harumitsu

    2011-12-01

    To elucidate the role of the prefrontal cortex in cognitive control of reaching movements, by multichannel near-infrared spectroscopy we examine changes in oxygenated hemoglobin (oxy-Hb) as an indicator of changes in regional cerebral blood flow in the bilateral dorsolateral (DLPFC), ventrolateral prefrontal cortex (VLPFC), and frontopolar cortex (FPC) during a reaching task with normal visual feedback (a consistent task) and a reaching task with flipped horizontal visual feedback (an inconsistent task). Subjects first perform 12 trials of the consistent task, and then perform six blocks of the inconsistent task, each of which consists of six trials. During the consistent task, oxy-Hb is increased only in the right VLPFC. During the first block of the inconsistent task, increases in oxy-Hb are observed in the bilateral DLPFC and the right VLPFC, whereas the increased oxy-Hb was gradually reduced as the block proceeded, which was accompanied by an improvement in the task performance. Eventually, there were no differences in the degree of change in oxy-Hb between the consistent and inconsistent tasks in the DLPFC and VLPFC. These findings suggest that the DLPFC is engaged in higher order cognitive control, while the right VLPFC is engaged in both higher and lower order cognitive controls.

  6. The role of transcranial magnetic stimulation in evaluation of motor cortex excitability in Rett syndrome.

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    Krajnc, Natalija; Zidar, Janez

    2016-07-01

    Rett syndrome (RTT) is a frequent neurodevelopmental disorder confirmed by clinical criteria and supported by the methyl-CpG-binding protein 2 gene (MECP2) mutation. A short central motor conduction time (CMCT) was reported in transcranial magnetic stimulation (TMS) studies performed in RTT. This was attributed to hyperexcitability of the motor cortex and/or spinal motor neurons, but was not studied further. We performed TMS in RTT to evaluate motor cortex excitability by determining the cortical motor threshold (CMT) and motor cortex inhibition by the cortical silent period (CSP) besides measuring CMCT. Single-pulse TMS was performed in 17 Rett patients, diagnosed by clinical criteria and MECP2 mutation testing, and the same number of healthy controls. The outcome measures were compared between RTT groups with different antiepileptic drugs (AED) and those with and without the MECP2 mutation. CMCT was shorter, but we found elevated CMT and shorter CSP, which suggests decreased excitatory and inhibitory motor cortical function. The outcome was independent of AED and the presence or absence of the MECP2 mutation. Decreased excitatory and inhibitory motor cortical function could explain the short CMCT, with higher stimulus intensities needed to excite pyramidal neurons. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Emotion regulation in spider phobia: role of the medial prefrontal cortex

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    Schäfer, Axel; Walter, Bertram; Stark, Rudolf; Vaitl, Dieter; Schienle, Anne

    2009-01-01

    Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions. PMID:19398537

  8. The role of the medial prefrontal cortex in the conditioning and extinction of fear

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  9. The role of parietal cortex in the formation of colour and motion based concepts

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    Samuel William Cheadle

    2014-07-01

    Full Text Available Imaging evidence shows that separate subdivisions of parietal cortex, in and around the intraparietal sulcus (IPS, are engaged when stimuli are grouped according to colour and to motion (Zeki and Stutters 2013. Since grouping is an essential step in the formation of concepts, we wanted to learn whether parietal cortex is also engaged in the formation of concepts according to these two attributes. Using functional magnetic resonance imaging (fMRI, and choosing the recognition of concept-based colour or motion stimuli as our paradigm, we found that there was strong concept-related activity in and around the intraparietal sulcus (IPS, a region whose homologue in the macaque monkey is known to receive direct but segregated anatomical inputs from V4 and V5. Parietal activity related to colour concepts was juxtaposed but did not overlap with activity related to motion concepts, thus emphasizing the continuation of the segregation of colour and motion into the conceptual system. Concurrent retinotopic mapping experiments showed that within the parietal cortex, concept-related activity increases within later stage IPS areas.

  10. Roles of the Different Sub-Regions of the Insular Cortex in Various Phases of the Decision-Making Process.

    Science.gov (United States)

    Droutman, Vita; Bechara, Antoine; Read, Stephen J

    2015-01-01

    This paper presents a coherent account of the role of the insular cortex (IC) in decision-making. We follow a conceptualization of decision-making that is very close to one previously proposed by Ernst and Paulus (2005): that the decision process is a progression of four phases: (1) re-focusing attention; (2) evaluation; (3) action; and (4) outcome processing, and we present evidence for the insula's role in all these phases. We review the existing work on insula's functional anatomy that subdivides the IC into posterior, dorsal anterior and ventral anterior regions. We re-map the results provided by the existing literature into these subdivisions wherever possible, to identify the components' role in each decision making phase. In addition, we identify a self-regulating quality of the IC focused on harm avoidance.

  11. [The motor organization of cerebral cortex and the role of the mirror neuron system. Clinical impact for rehabilitation].

    Science.gov (United States)

    Sallés, Laia; Gironès, Xavier; Lafuente, José Vicente

    2015-01-06

    The basic characteristics of Penfield homunculus (somatotopy and unique representation) have been questioned. The existence of a defined anatomo-functional organization within different segments of the same region is controversial. The presence of multiple motor representations in the primary motor area and in the parietal lobe interconnected by parieto-frontal circuits, which are widely overlapped, form a complex organization. Both features support the recovery of functions after brain injury. Regarding the movement organization, it is possible to yield a relevant impact through the understanding of actions and intentions of others, which is mediated by the activation of mirror-neuron systems. The implementation of cognitive functions (observation, image of the action and imitation) from the acute treatment phase allows the activation of motor representations without having to perform the action and it plays an important role in learning motor patterns. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  12. Dissociated roles of the inferior frontal gyrus and superior temporal sulcus in audiovisual processing: top-down and bottom-up mismatch detection.

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    Takeshi Uno

    Full Text Available Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG and superior temporal sulcus (STS are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA, which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.

  13. Dissociated roles of the inferior frontal gyrus and superior temporal sulcus in audiovisual processing: top-down and bottom-up mismatch detection.

    Science.gov (United States)

    Uno, Takeshi; Kawai, Kensuke; Sakai, Katsuyuki; Wakebe, Toshihiro; Ibaraki, Takuya; Kunii, Naoto; Matsuo, Takeshi; Saito, Nobuhito

    2015-01-01

    Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.

  14. Necessary Contributions of Human Frontal Lobe Subregions to Reward Learning in a Dynamic, Multidimensional Environment.

    Science.gov (United States)

    Vaidya, Avinash R; Fellows, Lesley K

    2016-09-21

    Real-world decisions are typically made between options that vary along multiple dimensions, requiring prioritization of the important dimensions to support optimal choice. Learning in this setting depends on attributing decision outcomes to the dimensions with predictive relevance rather than to dimensions that are irrelevant and nonpredictive. This attribution problem is computationally challenging, and likely requires an interplay between selective attention and reward learning. Both these processes have been separately linked to the prefrontal cortex, but little is known about how they combine to support learning the reward value of multidimensional stimuli. Here, we examined the necessary contributions of frontal lobe subregions in attributing feedback to relevant and irrelevant dimensions on a trial-by-trial basis in humans. Patients with focal frontal lobe damage completed a demanding reward learning task where options varied on three dimensions, only one of which predicted reward. Participants with left lateral frontal lobe damage attributed rewards to irrelevant dimensions, rather than the relevant dimension. Damage to the ventromedial frontal lobe also impaired learning about the relevant dimension, but did not increase reward attribution to irrelevant dimensions. The results argue for distinct roles for these two regions in learning the value of multidimensional decision options under dynamic conditions, with the lateral frontal lobe required for selecting the relevant dimension to associate with reward, and the ventromedial frontal lobe required to learn the reward association itself. The real world is complex and multidimensional; how do we attribute rewards to predictive features when surrounded by competing cues? Here, we tested the critical involvement of human frontal lobe subregions in a probabilistic, multidimensional learning environment, asking whether focal lesions affected trial-by-trial attribution of feedback to relevant and irrelevant

  15. The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology.

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    Hiser, Jaryd; Koenigs, Michael

    2018-04-15

    The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats.

    Science.gov (United States)

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

    2015-04-01

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

  17. Analysis of haptic information in the cerebral cortex

    Science.gov (United States)

    2016-01-01

    Haptic sensing of objects acquires information about a number of properties. This review summarizes current understanding about how these properties are processed in the cerebral cortex of macaques and humans. Nonnoxious somatosensory inputs, after initial processing in primary somatosensory cortex, are partially segregated into different pathways. A ventrally directed pathway carries information about surface texture into parietal opercular cortex and thence to medial occipital cortex. A dorsally directed pathway transmits information regarding the location of features on objects to the intraparietal sulcus and frontal eye fields. Shape processing occurs mainly in the intraparietal sulcus and lateral occipital complex, while orientation processing is distributed across primary somatosensory cortex, the parietal operculum, the anterior intraparietal sulcus, and a parieto-occipital region. For each of these properties, the respective areas outside primary somatosensory cortex also process corresponding visual information and are thus multisensory. Consistent with the distributed neural processing of haptic object properties, tactile spatial acuity depends on interaction between bottom-up tactile inputs and top-down attentional signals in a distributed neural network. Future work should clarify the roles of the various brain regions and how they interact at the network level. PMID:27440247

  18. The role of α-E-catenin in cerebral cortex development: radial glia specific effect on neuronal migration

    Directory of Open Access Journals (Sweden)

    Marie-Theres eSchmid

    2014-08-01

    Full Text Available During brain development, radial glial cells possess an apico-basal polarity and are coupled by adherens junctions to an F-actin belt. To elucidate the role of the actin, we conditionally deleted the key component α-E-catenin in the developing cerebral cortex. Deletion at early stages resulted in severe disruption of tissue polarity due to uncoupling of adherens junctions with the intracellular actin fibers leading to the formation of subcortical band heterotopia. Interestingly, this phenotype closely resembled the phenotype obtained by conditional RhoA deletion, both in regard to the macroscopic subcortical band heterotopia and the subcellular increase in G-actin/F-actin ratio. These data therefore together corroborate the role of the actin cytoskeleton and its anchoring to the adherens junctions for neuronal migration disorders.

  19. Distinct Roles for the Amygdala and Orbitofrontal Cortex in Representing the Relative Amount of Expected Reward.

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    Saez, Rebecca A; Saez, Alexandre; Paton, Joseph J; Lau, Brian; Salzman, C Daniel

    2017-07-05

    The same reward can possess different motivational meaning depending upon its magnitude relative to other rewards. To study the neurophysiological mechanisms mediating assignment of motivational meaning, we recorded the activity of neurons in the amygdala and orbitofrontal cortex (OFC) of monkeys during a Pavlovian task in which the relative amount of liquid reward associated with one conditioned stimulus (CS) was manipulated by changing the reward amount associated with a second CS. Anticipatory licking tracked relative reward magnitude, implying that monkeys integrated information about recent rewards to adjust the motivational meaning of a CS. Upon changes in relative reward magnitude, neural responses to reward-predictive cues updated more rapidly in OFC than amygdala, and activity in OFC but not the amygdala was modulated by recent reward history. These results highlight a distinction between the amygdala and OFC in assessing reward history to support the flexible assignment of motivational meaning to sensory cues. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Psychopathy, frustration, and reactive aggression: the role of ventromedial prefrontal cortex.

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    Blair, R J R

    2010-08-01

    Psychopathy is a developmental disorder marked by emotional hyporesponsiveness and an increased risk for instrumental and reactive aggression. The increased risk for reactive aggression is the focus of the current paper. It will be argued that the increased risk for reactive aggression does not relate to an increased sensitivity to threatening stimuli since psychopathy is associated with a reduced sensitivity to threat. Instead, it is argued that the increased risk for reactive aggression relates to an increased risk for frustration; i.e., the emotional state following the performance of an action in the expectation of a particular reward and not receiving this reward. Two impairments seen in psychopathy would increase the risk for frustration and consequent potential reactive aggression; impairments in stimulus-reinforcement learning and reversal learning. It is argued that both are known consequences of impairment in ventromedial prefrontal cortex, one of the regions principally implicated in psychopathy.

  1. Specifying the role of the left prefrontal cortex in word selection

    Science.gov (United States)

    Ries, S. K; Karzmark, C. R.; Navarrete, E.; Knight, R. T.; Dronkers, N. F.

    2015-01-01

    Word selection allows us to choose words during language production. This is often viewed as a competitive process wherein a lexical representation is retrieved among semantically-related alternatives. The left prefrontal cortex (LPFC) is thought to help overcome competition for word selection through top-down control. However, whether the LPFC is always necessary for word selection remains unclear. We tested 6 LPFC-injured patients and controls in two picture naming paradigms varying in terms of item repetition. Both paradigms elicited the expected semantic interference effects (SIE), reflecting interference caused by semantically-related representations in word selection. However, LPFC patients as a group showed a larger SIE than controls only in the paradigm involving item repetition. We argue that item repetition increases interference caused by semantically-related alternatives, resulting in increased LPFC-dependent cognitive control demands. The remaining network of brain regions associated with word selection appears to be sufficient when items are not repeated. PMID:26291289

  2. Dynamic modulation of short-term synaptic plasticity in the auditory cortex: the role of norepinephrine.

    Science.gov (United States)

    Salgado, Humberto; García-Oscos, Francisco; Dinh, Lu; Atzori, Marco

    2011-01-01

    Norepinephrine (NE) is an important modulator of neuronal activity in the auditory cortex. Using patch-clamp recording and a pair pulse protocol on an auditory cortex slice preparation we recently demonstrated that NE affects cortical inhibition in a layer-specific manner, by decreasing apical but increasing basal inhibition onto layer II/III pyramidal cell dendrites. In the present study we used a similar protocol to investigate the dependence of noradrenergic modulation of inhibition on stimulus frequency, using 1s-long train pulses at 5, 10, and 20 Hz. The study was conducted using pharmacologically isolated inhibitory postsynaptic currents (IPSCs) evoked by electrical stimulation of axons either in layer I (LI-eIPSCs) or in layer II/III (LII/III-eIPSCs). We found that: 1) LI-eIPSC display less synaptic depression than LII/III-eIPSCs at all the frequencies tested, 2) in both type of synapses depression had a presynaptic component which could be altered manipulating [Ca²+]₀, 3) NE modestly altered short-term synaptic plasticity at low or intermediate (5-10 Hz) frequencies, but selectively enhanced synaptic facilitation in LI-eIPSCs while increasing synaptic depression of LII/III-eIPSCs in the latest (>250 ms) part of the response, at high stimulation frequency (20 Hz). We speculate that these mechanisms may limit the temporal window for top-down synaptic integration as well as the duration and intensity of stimulus-evoked gamma-oscillations triggered by complex auditory stimuli during alertness. Published by Elsevier B.V.

  3. A Pilot Study of Mindfulness-Based Exposure Therapy in OEF/OIF Combat Veterans with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social–Emotional Processing

    Science.gov (United States)

    King, Anthony P.; Block, Stefanie R.; Sripada, Rebecca K.; Rauch, Sheila A. M.; Porter, Katherine E.; Favorite, Todd K.; Giardino, Nicholas; Liberzon, Israel

    2016-01-01

    Combat-related posttraumatic stress disorder (PTSD) is common among returning veterans, and is a serious and debilitating disorder. While highly effective treatments involving trauma exposure exist, difficulties with engagement and early drop may lead to sub-optimal outcomes. Mindfulness training may provide a method for increasing emotional regulation skills that may improve engagement in trauma-focused therapy. Here, we examine potential neural correlates of mindfulness training and in vivo exposure (non-trauma focused) using a novel group therapy [mindfulness-based exposure therapy (MBET)] in Afghanistan (OEF) or Iraq (OIF) combat veterans with PTSD. OEF/OIF combat veterans with PTSD (N = 23) were treated with MBET (N = 14) or a comparison group therapy [Present-centered group therapy (PCGT), N = 9]. PTSD symptoms were assessed at pre- and post-therapy with Clinician Administered PTSD scale. Functional neuroimaging (3-T fMRI) before and after therapy examined responses to emotional faces (angry, fearful, and neutral faces). Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but effect was not significantly different from PCGT (d = 0.43). Improvement in PTSD symptoms from pre- to post-treatment in both treatment groups was correlated with increased activity in rostral anterior cingulate cortex, dorsal medial prefrontal cortex (mPFC), and left amygdala. The MBET group showed greater increases in amygdala and fusiform gyrus responses to Angry faces, as well as increased response in left mPFC to Fearful faces. These preliminary findings provide intriguing evidence that MBET group therapy for PTSD may lead to changes in neural processing of social–emotional threat related to symptom reduction. PMID:27703434

  4. A Pilot Study of Mindfulness-Based Exposure Therapy in OEF/OIF Combat Veterans with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social-Emotional Processing.

    Science.gov (United States)

    King, Anthony P; Block, Stefanie R; Sripada, Rebecca K; Rauch, Sheila A M; Porter, Katherine E; Favorite, Todd K; Giardino, Nicholas; Liberzon, Israel

    2016-01-01

    Combat-related posttraumatic stress disorder (PTSD) is common among returning veterans, and is a serious and debilitating disorder. While highly effective treatments involving trauma exposure exist, difficulties with engagement and early drop may lead to sub-optimal outcomes. Mindfulness training may provide a method for increasing emotional regulation skills that may improve engagement in trauma-focused therapy. Here, we examine potential neural correlates of mindfulness training and in vivo exposure (non-trauma focused) using a novel group therapy [mindfulness-based exposure therapy (MBET)] in Afghanistan (OEF) or Iraq (OIF) combat veterans with PTSD. OEF/OIF combat veterans with PTSD ( N  = 23) were treated with MBET ( N  = 14) or a comparison group therapy [Present-centered group therapy (PCGT), N  = 9]. PTSD symptoms were assessed at pre- and post-therapy with Clinician Administered PTSD scale. Functional neuroimaging (3-T fMRI) before and after therapy examined responses to emotional faces (angry, fearful, and neutral faces). Patients treated with MBET had reduced PTSD symptoms (effect size d  = 0.92) but effect was not significantly different from PCGT ( d  = 0.43). Improvement in PTSD symptoms from pre- to post-treatment in both treatment groups was correlated with increased activity in rostral anterior cingulate cortex, dorsal medial prefrontal cortex (mPFC), and left amygdala. The MBET group showed greater increases in amygdala and fusiform gyrus responses to Angry faces, as well as increased response in left mPFC to Fearful faces. These preliminary findings provide intriguing evidence that MBET group therapy for PTSD may lead to changes in neural processing of social-emotional threat related to symptom reduction.

  5. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  6. Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia.

    Science.gov (United States)

    White, Thomas P; Joseph, Verghese; Francis, Susan T; Liddle, Peter F

    2010-11-01

    A salience network, comprising bilateral insula and anterior cingulate cortex (ACC), is thought to play a role in recruiting relevant brain regions for the processing of sensory information. Here, we present a functional network connectivity (FNC) analysis of spatial networks identified during somatosensation, performed to test the hypothesis that salience network connectivity is disturbed during information processing in schizophrenia. 19 medicated individuals with schizophrenia and 19 matched healthy controls participated in a functional magnetic resonance imaging study. 100 Hz vibrotactile stimuli were presented to the right index fingertip while whole-head blood oxygenation level-dependent contrast gradient-echo echo-planar images were acquired. Six spatial components of interest were identified using group independent component analysis: (1) bilateral insula, superior temporal and precentral gyrus (INS); (2) dorsal ACC; (3) left dorsolateral frontal and parietal cortex (left central executive network (LCEN)); (4) right dorsolateral frontal and parietal cortex (RCEN); (5) ventromedial frontal cortex (FDMN); and (6) precuneus, posterior cingulate and angular gyrus (PDMN). Maximal-lagged correlation was examined between all pairwise combinations of components. Significantly reduced FNC was observed in schizophrenia compared to controls between: INS and ACC; INS and FDMN; and LCEN and PDMN. There was no evidence of increased FNC in schizophrenia. Reduced salience network connectivity during information processing in schizophrenia suggests disturbance to the system which effects changes between contextually-relevant functional brain states. This aberrance may provide a mechanistic explanation of several clinical features of the disorder. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Cognitive insight in first-episode schizophrenia: further evidence for a role of the ventrolateral prefrontal cortex.

    Science.gov (United States)

    Buchy, Lisa; Hawco, Colin; Joober, Ridha; Malla, Ashok; Lepage, Martin

    2015-08-01

    In people with psychoses, Self-Reflectiveness may rely on the right ventrolateral prefrontal cortex (VLPFC). We used functional magnetic resonance imaging (fMRI) and a novel virtual reality paradigm to evaluate the role of the VLPFC for Self-Reflectiveness in 25 first-episode of schizophrenia (FES) participants and 24 controls. Participants first viewed 20 characters each paired with a unique object/location, and later completed source memory judgements during fMRI scanning. Self-Reflectiveness, measured with the Beck Cognitive Insight Scale, was significantly and positively correlated to activation in bilateral VLPFC in FES, but not in controls, providing further evidence that the VLPFC supports Self-Reflectiveness in FES. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Human Frontal Lobes and AI Planning Systems

    Science.gov (United States)

    Levinson, Richard; Lum, Henry Jr. (Technical Monitor)

    1994-01-01

    Human frontal lobes are essential for maintaining a self-regulating balance between predictive and reactive behavior. This paper describes a system that integrates prediction and reaction based on neuropsychological theories of frontal lobe function. In addition to enhancing our understanding of deliberate action in humans' the model is being used to develop and evaluate the same properties in machines. First, the paper presents some background neuropsychology in order to set a general context. The role of frontal lobes is then presented by summarizing three theories which formed the basis for this work. The components of an artificial frontal lobe are then discussed from both neuropsychological and AI perspectives. The paper concludes by discussing issues and methods for evaluating systems that integrate planning and reaction.

  9. The role of prefrontal cortex in working memory: a mini review

    Directory of Open Access Journals (Sweden)

    Antonio Homero Lara

    2015-12-01

    Full Text Available A prominent account of prefrontal cortex (PFC function is that single neurons within the PFC maintain representations of task-relevant stimuli in working memory. Evidence for this view comes from studies in which subjects hold a stimulus across a delay lasting up to several seconds. Persistent elevated activity in the PFC has been observed in animal models as well as in humans performing these tasks. This persistent activity has been interpreted as evidence for the encoding of the stimulus itself in working memory. However, recent findings have posed a challenge to this notion. A number of recent studies have examined neural data from the PFC and posterior sensory areas, both at the single neuron level in primates, and at a larger scale in humans, and have failed to find encoding of stimulus information in the PFC during tasks with a substantial working memory component. Strong stimulus related information, however, was seen in posterior sensory areas. These results suggest that delay period activity in the PFC might be better understood not as a signature of memory storage per se, but as a top down signal that influences posterior sensory areas where the actual working memory representations are maintained.

  10. Potential Role of Synaptic Activity to Inhibit LTD Induction in Rat Visual Cortex

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    Matthew R. Stewart

    2016-01-01

    Full Text Available Long-term depression (LTD, a widely studied form of activity-dependent synaptic plasticity, is typically induced by prolonged low-frequency stimulation (LFS. Interestingly, LFS is highly effective in eliciting LTD in vitro, but much less so under in vivo conditions; the reasons for the resistance of the intact brain to express LTD are not well understood. We examined if levels of background electrocorticographic (ECoG activity influence LTD induction in the thalamocortical visual system of rats under very deep urethane anesthesia, inducing a brain state of reduced spontaneous cortical activity. Under these conditions, LFS applied to the lateral geniculate nucleus resulted in LTD of field postsynaptic potentials (fPSPs recorded in the primary visual cortex (V1. Pairing LFS with stimulation of the brainstem (pedunculopontine reticular formation resulted in the appearance of faster, more complex activity in V1 and prevented LTD induction, an effect that did not require muscarinic or nicotinic receptors. Reticular stimulation alone (without LFS had no effect on cortical fPSPs. These results show that excitation of the brainstem activating system blocks the induction of LTD in V1. Thus, higher levels of neural activity may inhibit depression at cortical synapses, a hypothesis that could explain discrepancies regarding LTD induction in previous in vivo and in vitro work.

  11. Benefits of physical exercise on the aging brain: the role of the prefrontal cortex.

    Science.gov (United States)

    Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

    2013-11-01

    Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15-86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

  12. The Role of NMDA Receptor Subtypes in Short-Term Plasticity in the Rat Entorhinal Cortex

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    Sophie E. L. Chamberlain

    2008-01-01

    Full Text Available We have previously shown that spontaneous release of glutamate in the entorhinal cortex (EC is tonically facilitated via activation of presynaptic NMDA receptors (NMDAr containing the NR2B subunit. Here we show that the same receptors mediate short-term plasticity manifested by frequency-dependent facilitation of evoked glutamate release at these synapses. Whole-cell patch-clamp recordings were made from layer V pyramidal neurones in rat EC slices. Evoked excitatory postsynaptic currents showed strong facilitation at relatively low frequencies (3 Hz of activation. Facilitation was abolished by an NR2B-selective blocker (Ro 25-6981, but unaffected by NR2A-selective antagonists (Zn2+, NVP-AAM077. In contrast, postsynaptic NMDAr-mediated responses could be reduced by subunit-selective concentrations of all three antagonists. The data suggest that NMDAr involved in presynaptic plasticity in layer V are exclusively NR1/NR2B diheteromers, whilst postsynaptically they are probably a mixture of NR1/NR2A, NR1/NR2B diheteromers and NR1/NR2A/NR2B triheteromeric receptors.

  13. Sequential roles of primary somatosensory cortex and posterior parietal cortex in tactile-visual cross-modal working memory: a single-pulse transcranial magnetic stimulation (spTMS) study.

    Science.gov (United States)

    Ku, Yixuan; Zhao, Di; Hao, Ning; Hu, Yi; Bodner, Mark; Zhou, Yong-Di

    2015-01-01

    Both monkey neurophysiological and human EEG studies have shown that association cortices, as well as primary sensory cortical areas, play an essential role in sequential neural processes underlying cross-modal working memory. The present study aims to further examine causal and sequential roles of the primary sensory cortex and association cortex in cross-modal working memory. Individual MRI-based single-pulse transcranial magnetic stimulation (spTMS) was applied to bilateral primary somatosensory cortices (SI) and the contralateral posterior parietal cortex (PPC), while participants were performing a tactile-visual cross-modal delayed matching-to-sample task. Time points of spTMS were 300 ms, 600 ms, 900 ms after the onset of the tactile sample stimulus in the task. The accuracy of task performance and reaction time were significantly impaired when spTMS was applied to the contralateral SI at 300 ms. Significant impairment on performance accuracy was also observed when the contralateral PPC was stimulated at 600 ms. SI and PPC play sequential and distinct roles in neural processes of cross-modal associations and working memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Apraxia, pantomime and the parietal cortex.

    Science.gov (United States)

    Niessen, E; Fink, G R; Weiss, P H

    2014-01-01

    Apraxia, a disorder of higher motor cognition, is a frequent and outcome-relevant sequel of left hemispheric stroke. Deficient pantomiming of object use constitutes a key symptom of apraxia and is assessed when testing for apraxia. To date the neural basis of pantomime remains controversial. We here review the literature and perform a meta-analysis of the relevant structural and functional imaging (fMRI/PET) studies. Based on a systematic literature search, 10 structural and 12 functional imaging studies were selected. Structural lesion studies associated pantomiming deficits with left frontal, parietal and temporal lesions. In contrast, functional imaging studies associate pantomimes with left parietal activations, with or without concurrent frontal or temporal activations. Functional imaging studies that selectively activated parietal cortex adopted the most stringent controls. In contrast to previous suggestions, current analyses show that both lesion and functional studies support the notion of a left-hemispheric fronto-(temporal)-parietal network underlying pantomiming object use. Furthermore, our review demonstrates that the left parietal cortex plays a key role in pantomime-related processes. More specifically, stringently controlled fMRI-studies suggest that in addition to storing motor schemas, left parietal cortex is also involved in activating these motor schemas in the context of pantomiming object use. In addition to inherent differences between structural and functional imaging studies and consistent with the dedifferentiation hypothesis, the age difference between young healthy subjects (typically included in functional imaging studies) and elderly neurological patients (typically included in structural lesion studies) may well contribute to the finding of a more distributed representation of pantomiming within the motor-dominant left hemisphere in the elderly.

  15. Visual Categorization and the Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Jamie K Fitzgerald

    2012-05-01

    Full Text Available The primate brain is adept at rapidly grouping items and events into functional classes, or categories, in order to recognize the significance of stimuli and guide behavior. Higher cognitive functions have traditionally been considered the domain of frontal areas. However, increasing evidence suggests that parietal cortex is also involved in categorical and associative processes. Previous work showed that the parietal cortex is highly involved in spatial processing, attention and saccadic eye movement planning, and more recent studies have found decision-making signals in LIP. We recently found that a subdivision of parietal cortex, the lateral intraparietal area (LIP, reflects learned categories for multiple types of visual stimuli. Additionally, a comparison of categorization signals in parietal and frontal areas found stronger and earlier categorization signals in parietal cortex, arguing that parietal abstract association or category signals are unlikely to arise via feedback from prefrontal cortex (PFC.

  16. [Brodmann Areas 8 and 9 Including the Frontal Eye Field].

    Science.gov (United States)

    Watanabe, Masataka

    2017-04-01

    Based on cytoarchitectonic analyses, Brodmann assigned numbers 8 and 9 to certain areas of the dorsal and medial prefrontal cortex (PFC) in humans and monkeys. Petrides and Pandya re-analyzed the cytoarchitectures of the human and monkey PFCs, and proposed slightly different brain maps for both species. They assigned numbers 8, 9 and 9/46 to the areas that were originally named areas 8 and 9. Areas 8 and 9 have both lateral and medial regions respectively. The lateral area 8 is important for conditional discrimination learning. The frontal eye field which occupies the most caudal region of area 8, is responsible for visual attention and control of eye movements. The lateral area 9 and area 9/46 are functionally similar to area 46 and play important roles in executive control. The dorsomedial prefrontal cortex (DMPFC) comprises the medial regions of areas 8 and 9 and is related to "Theory of Mind" and social cognition. The DMPFC is also known to show "default mode of brain activity" (i.e., more activity during rest than during cognitive task).

  17. Charting the Maturation of the Frontal Lobe: An Electrophysiological Strategy

    Science.gov (United States)

    Segalowitz, S. J.; Davies, Patricia L.

    2004-01-01

    Tracking the functional development of specific regions of the prefrontal cortex in children using event-related potentials (ERPs) is challenging for both technical and conceptual reasons. In this paper we outline our strategy for studying frontal lobe development and present preliminary results from children aged 7-17 years and young adults using…

  18. The Role of the Subgenual Anterior Cingulate Cortex and Amygdala in Environmental Sensitivity to Infant Crying

    Science.gov (United States)

    Mutschler, Isabella; Ball, Tonio; Kirmse, Ursula; Wieckhorst, Birgit; Pluess, Michael; Klarhöfer, Markus; Meyer, Andrea H.; Wilhelm, Frank H.; Seifritz, Erich

    2016-01-01

    Newborns and infants communicate their needs and physiological states through crying and emotional facial expressions. Little is known about individual differences in responding to infant crying. Several theories suggest that people vary in their environmental sensitivity with some responding generally more and some generally less to environmental stimuli. Such differences in environmental sensitivity have been associated with personality traits, including neuroticism. This study investigated whether neuroticism impacts neuronal, physiological, and emotional responses to infant crying by investigating blood-oxygenation-level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI) in a large sample of healthy women (N = 102) with simultaneous skin conductance recordings. Participants were repeatedly exposed to a video clip that showed crying infants and emotional responses (valence, arousal, and irritation) were assessed after every video clip presentation. Increased BOLD signal during the perception of crying infants was found in brain regions that are associated with emotional responding, the amygdala and anterior insula. Significant BOLD signal decrements (i.e., habituation) were found in the fusiform gyrus, middle temporal gyrus, superior temporal gyrus, Broca’s homologue on the right hemisphere, (laterobasal) amygdala, and hippocampus. Individuals with high neuroticism showed stronger activation in the amygdala and subgenual anterior cingulate cortex (sgACC) when exposed to infant crying compared to individuals with low neuroticism. In contrast to our prediction we found no evidence that neuroticism impacts fMRI-based measures of habituation. Individuals with high neuroticism showed elevated skin conductance responses, experienced more irritation, and perceived infant crying as more unpleasant. The results support the hypothesis that individuals high in neuroticism are more emotionally responsive, experience more negative emotions, and

  19. Neural network underlying ictal pouting ("chapeau de gendarme") in frontal lobe epilepsy.

    Science.gov (United States)

    Souirti, Zouhayr; Landré, Elisabeth; Mellerio, Charles; Devaux, Bertrand; Chassoux, Francine

    2014-08-01

    In order to determine the anatomical neural network underlying ictal pouting (IP), with the mouth turned down like a "chapeau de gendarme", in frontal lobe epilepsy (FLE), we reviewed the video-EEG recordings of 36 patients with FLE who became seizure-free after surgery. We selected the cases presenting IP, defined as a symmetrical and sustained (>5s) lowering of labial commissures with contraction of chin, mimicking an expression of fear, disgust, or menace. Ictal pouting was identified in 11 patients (8 males; 16-48 years old). We analyzed the clinical semiology, imaging, and electrophysiological data associated with IP, including FDG-PET in 10 and SEEG in 9 cases. In 37 analyzed seizures (2-7/patient), IP was an early symptom, occurring during the first 10s in 9 cases. The main associated features consisted of fear, anguish, vegetative disturbances, behavioral disorders (sudden agitation, insults, and fighting), tonic posturing, and complex motor activities. The epileptogenic zone assessed by SEEG involved the mesial frontal areas, especially the anterior cingulate cortex (ACC) in 8 patients, whereas lateral frontal onset with an early spread to the ACC was seen in the other patient. Ictal pouting associated with emotional changes and hypermotor behavior had high localizing value for rostroventral "affective" ACC, whereas less intense facial expressions were related to the dorsal "cognitive" ACC. Fluorodeoxyglucose positron emission tomography demonstrated the involvement of both the ACC and lateral cortex including the anterior insula in all cases. We propose that IP is sustained by reciprocal mesial and lateral frontal interactions involved in emotional and cognitive processes, in which the ACC plays a pivotal role. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Role of medial prefrontal cortex serotonin 2A receptors in the control of retrieval of recognition memory in rats.

    Science.gov (United States)

    Bekinschtein, Pedro; Renner, Maria Constanza; Gonzalez, Maria Carolina; Weisstaub, Noelia

    2013-10-02

    Often, retrieval cues are not uniquely related to one specific memory, which could lead to memory interference. Controlling interference is particularly important during episodic memory retrieval or when remembering specific events in a spatiotemporal context. Despite a clear involvement of prefrontal cortex (PFC) in episodic memory in human studies, information regarding the mechanisms and neurotransmitter systems in PFC involved in memory is scarce. Although the serotoninergic system has been linked to PFC functionality and modulation, its role in memory processing is poorly understood. We hypothesized that the serotoninergic system in PFC, in particular the 5-HT2A receptor (5-HT2AR) could have a role in the control of memory retrieval. In this work we used different versions of the object recognition task in rats to study the role of the serotoninergic modulation in the medial PFC (mPFC) in memory retrieval. We found that blockade of 5-HT2AR in mPFC affects retrieval of an object in context memory in a spontaneous novelty preference task, while sparing single-item recognition memory. We also determined that 5-HT2ARs in mPFC are required for hippocampal-mPFC interaction during retrieval of this type of memory, suggesting that the mPFC controls the expression of memory traces stored in the hippocampus biasing retrieval to the most relevant one.

  1. Reversible Inactivation of Rat Premotor Cortex Impairs Temporal Preparation, but not Inhibitory Control, During Simple Reaction-Time Performance.

    Science.gov (United States)

    Smith, Nathaniel J; Horst, Nicole K; Liu, Benjamine; Caetano, Marcelo S; Laubach, Mark

    2010-01-01

    Previous studies by our lab and others have established a role for medial areas of the prefrontal cortex (mPFC) in the top-down control of action during simple reaction-time (RT) tasks. However, the neural circuits that allow mPFC to influence activity in the motor system have remained unclear. In the present study, we used a combination of tract-tracing and reversible inactivation methods to examine the role of a motor-related area in the rat frontal cortex, called the rostral forelimb area (RFA), in the top-down control of action. Neural tracing studies involved used electrical microstimulation to identify RFA and injections of biotinylated dextran amines (BDA) to map out connections of RFA with other parts of the frontal cortex. Connections were found between RFA and mPFC, the agranular insular cortex, and the primary motor cortex. Reversible inactivations using muscimol infusions into RFA increased response times and eliminated delay-dependent speeding, but did not increase premature responding. These results are markedly different from what is obtained when muscimol is infused into mPFC, which leads to excessive premature responding and a reduction of RTs to stimuli at short delays (Narayanan et al., 2006). We also tested animals during the RT task after inactivating the agranular insular cortex, which contains neurons that projects to and receives from RFA and mPFC, and found no effects on RT performance. Together, these studies suggest that RFA is a premotor region in the rat frontal cortex that competes with mPFC to control action selection. We suggest that RFA controls the threshold that is used to initiate responding and generates prepotent excitation over responding that is crucial for temporal preparation.

  2. The role of the human extrastriate visual cortex in mirror symmetry discrimination: a TMS-adaptation study.

    Science.gov (United States)

    Cattaneo, Zaira; Mattavelli, Giulia; Papagno, Costanza; Herbert, Andrew; Silvanto, Juha

    2011-10-01

    The human visual system is able to efficiently extract symmetry information from the visual environment. Prior neuroimaging evidence has revealed symmetry-preferring neuronal representations in the dorsolateral extrastriate visual cortex; the objective of the present study was to investigate the necessity of these representations in symmetry discrimination. This was accomplished by the use of state-dependent transcranial magnetic stimulation, which combines the fine resolution of adaptation paradigms with the assessment of causality. Subjects were presented with adapters and targets consisting of dot configurations that could be symmetric along either the vertical or horizontal axis (or they could be non-symmetric), and they were asked to perform a symmetry discrimination task on the targets while fixating the center of the screen. TMS was applied during the delay between the adapter and the test stimulus over one of four different sites: Left or Right V1/V2, or left or right dorsolateral extrastriate cortex (DLO). TMS over both Left and Right DLO reduced the adaptation effect in detecting vertical and horizontal symmetry, although the Left DLO effect on horizontal symmetry and the Right DLO effect on both vertical and horizontal symmetry were present only when considering subjects who showed a behavioral adaptation effect in the baseline No-TMS condition. Application of TMS over the Left or Right V1/V2 did not modulate the adaptation effect. Overall, these data suggest that both the Left and Right DLO contain neuronal representations tuned to mirror symmetry which play a causal role in symmetry discrimination. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  4. Role of direct vs indirect pathways from the motor cortex to spinal motoneurons in the control of hand dexterity

    Directory of Open Access Journals (Sweden)

    Tadashi eIsa

    2013-11-01

    Full Text Available Evolutionally, development of the direct connection from the motor cortex to spinal motoneurons (corticomotoneuronal (CM pathway parallels the ability of hand dexterity. Damage to the corticofugal fibers in higher primates resulted in deficit of fractionated digit movements. Based on such observations, it was generally believed that the CM pathway plays a critical role in the control of hand dexterity. On the other hand, a number of phylogenetically older indirect pathways from the motor cortex to motoneurons still exist in primates. The indirect pathways are mediated by intercalated neurons such as segmental interneurons (sINs, propriospinal neurons (PNs reticulospinal neurons (RSNs or rubrospinal neurons (RuSNs. However, their contribution to hand dexterity remains elusive. Lesion of the brainstem pyramid sparing the transmission through the RuSNs and RSNs, resulted in permanent deficit of fractionated digit movements in macaque monkeys. On the other hand, in our recent study, after lesion of the dorsolateral funiculus (DLF at the C5 segment, which removed the CM pathway and the transmission through sINs and RuSNs but spared the processing through the PNs and RSNs, fractionated digit movements recovered within several weeks. These results suggest that the PNs can be involved in the recovery of fractionated digit movements, but the RSNs and RuSNs have less capacity in this regard. However, on closer inspection, it was found that the activation pattern of hand and arm muscles considerably changed after the C5 lesion, suggesting limitation of PNs for the compensation of hand dexterity. Altogether, it is suggested that PNs, RSNs RuSNs and the CM pathway (plus sINs make a different contribution to the hand dexterity and appearance of motor deficit of the hand dexterity caused by damage to the corticofugal fibers and potential of recovery varies depending on the rostrocaudal level of the lesion.

  5. Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory.

    Science.gov (United States)

    Plakke, Bethany; Hwang, Jaewon; Romanski, Lizabeth M

    2015-07-01

    The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that

  6. The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex.

    Science.gov (United States)

    Liu, Wei; Ge, Tongtong; Leng, Yashu; Pan, Zhenxiang; Fan, Jie; Yang, Wei; Cui, Ranji

    2017-01-01

    Neural plasticity, a fundamental mechanism of neuronal adaptation, is disrupted in depression. The changes in neural plasticity induced by stress and other negative stimuli play a significant role in the onset and development of depression. Antidepressant treatments have also been found to exert their antidepressant effects through regulatory effects on neural plasticity. However, the detailed mechanisms of neural plasticity in depression still remain unclear. Therefore, in this review, we summarize the recent literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these findings may pave the way for future progress in neural plasticity studies.

  7. The role of plastic changes in the motor cortex and spinal cord for motor learning

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Lundbye-Jensen, Jesper

    2010-01-01

    are key players in the early stages of skill acquisition and consolidation of motor learning. Expansion of the cortical representation of the trained muscles, changes in corticomuscular coupling and changes in stretch reflex activity are thus all markers of neuroplastic changes accompanying early skill...... acquisition. We have shown in recent experiments that sensory feedback from the active muscles play a surprisingly specific role at this stage of learning. Following motor skill training, repeated activation of sensory afferents from the muscle that has been involved in a previous training session, interfered...... the consolidation of increased performance of a different previously trained task involving the same movement direction and muscle group, whereas training of other muscles had no effect. This emphasizes the role of specific sensory error signals in the acquisition of new motor skills and illustrates the functional...

  8. Repetitive TMS suggests a role of the human dorsal premotor cortex in action prediction

    Directory of Open Access Journals (Sweden)

    Waltraud eStadler

    2012-02-01

    Full Text Available Predicting the actions of other individuals is crucial for our daily interactions. Recent evidence suggests that the prediction of object-directed arm and full-body actions employs the PMd. Thus, the neural substrate involved in action control may also be essential for action prediction. Here, we aimed to address this issue and hypothesised that disrupting the PMd impairs action prediction. Using fMRI-guided coil navigation, rTMS (5 pulses, 10 Hz was applied over the left PMd and over the vertex (control region while participants observed everyday actions in video clips that were transiently occluded for one second. The participants detected manipulations in the time course of occluded actions, which required them to internally predict the actions during occlusion. To differentiate between functional roles that the PMd could play in prediction, rTMS was either delivered at occluder onset (TMS-early, affecting the initiation of action prediction, or 300 ms later during occlusion (TMS-late, affecting the maintenance of an ongoing prediction. TMS-early over the left PMd produced more prediction errors than TMS-early over the vertex. TMS-late had no effect on prediction performance, suggesting that the left PMd might be involved particularly during the initiation of internally guided action prediction but may play a subordinate role in maintaining ongoing prediction. These findings open a new perspective on the role of the left PMd in action prediction which is in line with its functions in action control and in cognitive tasks. In the discussion, the relevance of the left PMd for integrating external action parameters with the observer’s motor repertoire is emphasised. Overall, the results are in line with the notion that premotor functions are employed in both action control and action observation.

  9. Neural mechanisms of the testosterone-aggression relation: the role of orbitofrontal cortex.

    Science.gov (United States)

    Mehta, Pranjal H; Beer, Jennifer

    2010-10-01

    Testosterone plays a role in aggressive behavior, but the mechanisms remain unclear. The present study tested the hypothesis that testosterone influences aggression through the OFC, a region implicated in self-regulation and impulse control. In a decision-making paradigm in which people chose between aggression and monetary reward (the ultimatum game), testosterone was associated with increased aggression following social provocation (rejecting unfair offers). The effect of testosterone on aggression was explained by reduced activity in the medial OFC. The findings suggest that testosterone increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation.

  10. Mesial frontal lobe epilepsy.

    Science.gov (United States)

    Unnwongse, Kanjana; Wehner, Tim; Foldvary-Schaefer, Nancy

    2012-10-01

    Mesial frontal lobe epilepsies can be divided into epilepsies arising from the anterior cingulate gyrus and those of the supplementary sensorimotor area. They provide diagnostic challenges because they often lack lateralizing or localizing features on clinical semiology and interictal and ictal scalp electroencephalographic (EEG) recordings. A number of unique semiologic features have been described over the last decade in patients with mesial frontal lobe epilepsy (FLE). There are few reports of applying advanced neurophysiologic techniques such as electrical source imaging, magnetoencephalography, EEG/functional magnetic resonance imaging, or analysis of high-frequency oscillations in patients with mesial FLE. Despite these diagnostic challenges, it seems that patients with mesial FLE benefit from epilepsy surgery to the same extent or even better than patients with FLE do, as a whole.

  11. Consistent pivotal role of posterior cingulate cortex in the default mode network revealed by partial correlation analysis

    Science.gov (United States)

    Li, Rui; Li, Juan; Miao, Xiaoyan; Yao, Li; Wu, Xia

    2010-03-01

    Resting-state functional MRI (fMRI) studies have suggested the posterior cingulate cortex (PCC) plays a pivotal role in the default mode network (DMN), a set of co-activated brain regions characterizing the resting-state brain. Concerning this finding we propose the following questions in this study: Does PCC consistently play the equally crucial role in the DMN across different subjects, such as healthy young and healthy old subjects? Whether the fMRI scan environments or parameters would affect the results? To address these questions, we collected resting-state fMRI data on four groups of subjects: two healthy young groups scanned under 3-T and 1.5-T MRI systems respectively, and two healthy elderly groups both scanned under 3-T MRI system but with different scan parameters. Then group independent component analysis was used to isolate the DMN, and partial correlation analysis was employed to reveal the direct interactions between brain regions from the DMN. Finally, we measured the connectivity between brain regions based on the number of significantly interacted links to every region within this network. We found that PCC was the brain region consistently having the largest number of directly interacted regions in the four groups, suggesting the pivotal role of PCC in the DMN was stable and consistent across healthy subjects. The results also suggested the function of PCC would be more critical in healthy elderly subjects compared with healthy young subjects. And the factors of scan environments and parameters did not show any obvious impact on the above conclusions in this investigation.

  12. Posttraumatic frontal bone osteomyelitis.

    Science.gov (United States)

    Jung, S Heredero; Aniceto, G Sánchez; Rodríguez, I Zubillaga; Diaz, R Gutiérrez; Recuero, I I García

    2009-05-01

    We present the clinical case of a patient with open bilateral frontal sinus fractures who developed a frontal osteomyelitis. A review of the problem and management ascending to the different alternatives for central anterior skull base defects and fronto-orbital reconstruction is also presented. After extensive radical debridement of the necrotic bone, final reconstruction of the skull base was performed by using a rectus abdominis free flap. A custom-made hard tissue replacement implant was used for the fronto-orbital reconstruction. Extensive debridement is required for the treatment of frontal osteomyelitis. An appropriate isolation of the skull base from the upper aerodigestive system must be obtained to prevent continuous infectious complications. Free flaps are especially useful for skull base reconstruction when traditional methods are not available or have failed because of the lack of available tissue for vascularized reconstruction. Custom-made alloplastic implants are a good reconstructive option for large fronto-orbital defects once the infection is gone and vascularized tissue has been transferred.

  13. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    International Nuclear Information System (INIS)

    Moll, Jorge; Oliveira-Souza, Ricardo de

    2001-01-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  14. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Moll, Jorge [LABS and Rede D' Or Hospitais, Rio de Janeiro RJ (Brazil). Grupo de Neuroimagem e Neurologia do Comportamento; Eslinger, Paul J. [Pensylvania State Univ. (United States). College of Medicine. Div. of Neurology and Behavioral Science; The Milton S. Hershey Medical Center, Hershey, PN (United States); Oliveira-Souza, Ricardo de [Universidade do Rio de Janeiro (UNI-Rio), RJ (Brazil). Hospital Universitario Gaffree e Guinle]. E-mail: neuropsychiatry@hotmail.com

    2001-09-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  15. The role of Long-Range Connectivity for the Characterization of the Functional-Anatomical Organization of the Cortex

    Directory of Open Access Journals (Sweden)

    Thomas R Knösche

    2011-07-01

    Full Text Available This review focuses on the role of long-range connectivity as one element of brain structure that is of key importance for the functional-anatomical organization of the cortex. In this context, we discuss the putative guiding principles for mapping brain function and structure onto the cortical surface. Such mappings reveal a high-degree of functional-anatomical segregation. Given that brain regions frequently maintain characteristic connectivity profiles and the functional repertoire of a cortical area is closely related to its anatomical connections, long-range connectivity may be used to define segregated cortical areas. This methodology is called connectivity-based parcellation.Within this framework, we investigate different techniques to estimate connectivity profiles with emphasis given to non-invasive methods based on diffusion magnetic resonance imaging (dMRI and diffusion tractography. Cortical parcellation is then defined based on similarity between diffusion tractograms, and different clustering approaches are discussed.We conclude that the use of non-invasively acquired connectivity estimates to characterize the functional-anatomical organization of the brain is a valid, relevant and necessary endeavor. Current and future developments in dMRI technology, tractography algorithms and models of the similarity structure hold great potential for a substantial improvement and enrichment of the results of the technique.

  16. Neurobiological foundations of multisensory processing integration in people with autism spectrum disorders: The role of the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Sonia eMartínez-Sanchis

    2014-12-01

    Full Text Available This review aims to relate the sensory processing problems in people with Autism spectrum disorders (ASD, especially Multisensory interaction (MSI, to the role of the medial prefrontal cortex (mPFC by exploring neuroanatomical findings; brain connectivity and Default Network (DN; global or locally directed attention; and temporal multisensory binding. The mPFC is part of the brain’s DN, which is deactivated when attention is focused on a particular task and activated on rest when spontaneous cognition emerges. In those with ASD, it is hypoactive and the higher the social impairment the greater the atypical activity. With an immature DN, cross-modal integration is impaired, resulting in a collection of disconnected fragments instead of a coherent global perception. The deficit in MSI may lie in the temporal synchronization of neural networks. The time interval in which the stimulation of one sensory channel could influence another would be higher, preventing integration in the typical shorter time range. Thus, the underconnectivity between distant brain areas would be involved in top-down information processes (relying on global integration of data from different sources and would enhance low level perception processes such as over focused attention to sensory details.

  17. Role of dopamine on functional recovery in the contralateral hemisphere after focal stroke in the somatosensory cortex.

    Science.gov (United States)

    Obi, Kisho; Amano, Izuki; Takatsuru, Yusuke

    2018-01-01

    Functional recovery after a stroke is important for patients' quality of life. Not only medical care during the acute phase, but also rehabilitation during the chronic phase after a stroke is important. However, the mechanisms underlying functional recovery, particularly the chronic phase after stroke, are still not fully understood. Thus, further basic study on brain after focal stroke is necessary. In this study, we found that the concentration of dopamine (DA) increased during first week after a stroke in the hemisphere contralateral in the site of stroke by in vivo microdialysis. When we applied haloperidol (HPD), a potent DA receptor blocker, functional recovery was inhibited. Interestingly, administration of aripiprazole (ARP), a novel partial agonist of the DA receptor, during the chronic phase improved the remodeling of neuronal circuits in somatosensory cortex (SSC). These findings indicate that the DAergic system play a critical role in functional compensation by the non-infarcted hemisphere after a focal stroke in SSC. It is also revealed that administration of HPD/ARP to stroke patients affects functional recovery after a stroke, and stimulation of the DAergic system during the chronic phase of stroke potentially benefits stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

    Science.gov (United States)

    Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

    2016-02-01

    Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. Parieto-frontal gradients and domains underlying eye and hand operations in the action space.

    Science.gov (United States)

    Battaglia-Mayer, Alexandra; Babicola, Lucy; Satta, Eleonora

    2016-10-15

    In monkeys, motor intention in its different forms emerges from a parietal-frontal gradient of visual, eye and hand signals, containing discrete dominant domains. These are formed by areas sharing cortical connections and functional properties. Within this gradient, the combination of different inputs determines the tuning properties of neurons, while local and long cortico-cortical connections shape the structure and temporal delays of the network. The pathways linking similar functional domains in parietal and frontal cortex sculpt information processing systems related to different functions, all requiring eye-hand coordination. fMRI experiments show that similar gradients lay at the core of cognitive-motor control in humans as well. This eye-hand matrix provides a framework to address, within a unitary frame, not only basic forms of motor behavior, such as reaching and grasping, but also actions of increasing complexity, such as interception of moving targets, tool use, construction of complex objects, maze analysis and solution, among others. The organization of the cerebral cortex into functional gradients and domains, beyond frontal and parietal cortices, is common to other brain regions, such as prefrontal cortex and hippocampus, and does not support views of the parieto-frontal operations based on specific and strictly segregated eye and hand modules. These can only be found at the eye and hand motor output domains in the frontal cortex, that is in the frontal eye fields and in the primary motor cortex, respectively. Copyright © 2016. Published by Elsevier Ltd.

  20. Infant Frontal Asymmetry Predicts Child Emotional Availability

    Science.gov (United States)

    Licata, Maria; Paulus, Markus; Kühn-Popp, Nina; Meinhardt, Jorg; Sodian, Beate

    2015-01-01

    While factors influencing maternal emotional availability (EA) have been well investigated, little is known about the development of child EA. The present longitudinal study investigated the role of frontal brain asymmetry in young children with regard to child EA (child responsiveness and involvement) in mother-child interaction in a sample of 28…

  1. Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

    Science.gov (United States)

    Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

    2015-01-28

    Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.

  2. Frontal and striatal alterations associated with psychopathic traits in adolescents

    Science.gov (United States)

    Yang, Yaling; Narr, Katherine L.; Baker, Laura A.; Joshi, Shantanu H.; Jahanshad, Neda; Raine, Adrian; Thompson, Paul M.

    2016-01-01

    Neuroimaging research has demonstrated a range of structural deficits in adults with psychopathy, but little is known about structural correlates of psychopathic tendencies in adolescents. Here we examined structural magnetic resonance imaging (sMRI) data obtained from 14-year-old adolescents (n=108) using tensor-based morphometry (TBM) to isolate global and localized differences in brain tissue volumes associated with psychopathic traits in this otherwise healthy developmental population. We found that greater levels of psychopathic traits were correlated with increased brain tissue volumes in the left putamen, left ansa peduncularis, right superiomedial prefrontal cortex, left inferior frontal cortex, right orbitofrontal cortex, and right medial temporal regions and reduced brain tissues volumes in the right middle frontal cortex, left superior parietal lobule, and left inferior parietal lobule. Post hoc analyses of parcellated regional volumes also showed putamen enlargements to correlate with increased psychopathic traits. Consistent with earlier studies, findings suggest poor decision-making and emotional dysregulation associated with psychopathy may be due, in part, to structural anomalies in frontal and temporal regions whereas striatal structural variations may contribute to sensation-seeking and reward-driven behavior in psychopathic individuals. Future studies will help clarify how disturbances in brain maturational processes might lead to the developmental trajectory from psychopathic tendencies in adolescents to adult psychopathy. PMID:25676553

  3. Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence.

    Science.gov (United States)

    Cavanagh, James F; Shackman, Alexander J

    2015-01-01

    Evidence from imaging and anatomical studies suggests that the midcingulate cortex (MCC) is a dynamic hub lying at the interface of affect and cognition. In particular, this neural system appears to integrate information about conflict and punishment in order to optimize behavior in the face of action-outcome uncertainty. In a series of meta-analyses, we show how recent human electrophysiological research provides compelling evidence that frontal-midline theta signals reflecting MCC activity are moderated by anxiety and predict adaptive behavioral adjustments. These findings underscore the importance of frontal theta activity to a broad spectrum of control operations. We argue that frontal-midline theta provides a neurophysiologically plausible mechanism for optimally adjusting behavior to uncertainty, a hallmark of situations that elicit anxiety and demand cognitive control. These observations compel a new perspective on the mechanisms guiding motivated learning and behavior and provide a framework for understanding the role of the MCC in temperament and psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

    International Nuclear Information System (INIS)

    Schliebs, R.; Walch, C.

    1989-01-01

    The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author)

  5. Benefit of the doubt: a new view of the role of the prefrontal cortex in executive functioning and decision making

    Science.gov (United States)

    Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Denburg, Natalie L.; Tranel, Daniel

    2013-01-01

    The False Tagging Theory (FTT) is a neuroanatomical model of belief and doubt processes that proposes a single, unique function for the prefrontal cortex. Here, we review evidence pertaining to the FTT, the implications of the FTT regarding fractionation of the prefrontal cortex, and the potential benefits of the FTT for new neuroanatomical conceptualizations of executive functions. The FTT provides a parsimonious account that may help overcome theoretical problems with prefrontal cortex mediated executive control such as the homunculus critique. Control in the FTT is examined via the “heuristics and biases” psychological framework for human judgment. The evidence indicates that prefrontal cortex mediated doubting is at the core of executive functioning and may explain some biases of intuitive judgments. PMID:23745103

  6. Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

    Science.gov (United States)

    Holec, Victoria; Pirot, Heather L.; Euston, David R.

    2014-01-01

    The rat anterior cingulate cortex (ACC) mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., “courage”). As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm (HRA) but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the HRA. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain tasks. PMID:24478659

  7. Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

    Directory of Open Access Journals (Sweden)

    Victoria eHolec

    2014-01-01

    Full Text Available The rat anterior cingulate cortex (ACC mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., courage. As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the high reward arm. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain

  8. Role of Nitric Oxide in Radioinduced Effects in Developing Brain Cortex

    International Nuclear Information System (INIS)

    Robello, E

    2001-01-01

    different from controls neither.Although these results suggest it might be possible that NOS mRNAs do not vary after irradiation, more experiments ought to be made in order to find conclusive data. All in all, in spite of NO may increase the number of frees radicals and ROS determining a very important cellular injury trough oxidative stress in several systems, NO may play a completely different role in developing neurones.It could be mainly by mediating neuroprotective effects trough avoiding lipid peroxidation in vivo, due to that it cannot be detected any alteration neither in ascorbyl radical/ascorbic acid ratio nor in lipid radicals content in developing rat brain.Moreover, it has been shown that apoptosis rate goes down in cultures which have been exposed to ionising radiation in the presence of NO donors. And, finally, it can be concluded that the increase in NO concentration may be determined by an enhancement in NOS activity, trough a post-transcriptional or post-translational modification or by NO releasing from an intracellular or extracellular compartment

  9. Dorsolateral frontal lobe epilepsy.

    Science.gov (United States)

    Lee, Ricky W; Worrell, Greg A

    2012-10-01

    Dorsolateral frontal lobe seizures often present as a diagnostic challenge. The diverse semiologies may not produce lateralizing or localizing signs and can appear bizarre and suggest psychogenic events. Unfortunately, scalp electroencephalographic (EEG) and magnetic resonance imaging (MRI) are often unsatisfactory. It is not uncommon that these traditional diagnostic studies are either unhelpful or even misleading. In some cases, SPECT and positron emission tomography imaging can be an effective tool to identify the origin of seizures. However, these techniques and other emerging techniques all have limitations, and new approaches are needed to improve source localization.

  10. Frontal Integration and Coping

    DEFF Research Database (Denmark)

    Larsen, Torben

    2012-01-01

    and risk minimizing Rationalists dominated by dlPFC • R correlates both with your own level of education and that of your parents 3 Conclusion: Empirical verification of the first derivative of NeM uncovers four different coping patterns within the range of normal behaviors with an obvious analogue...... to the classical tempers. In prospect, differentiating the Frontal integration pattern by temper (General risk attitude) opens an evidence-based pathway for individually tailored neural training towards advanced social objectives as multidisciplinary collaboration and healthy living. References 1. Larsen T...... et al. Gender difference in neural response to psychological stress. SCAN 2 2007, 227–233...

  11. The causal role of category-specific neuronal representations in the left ventral premotor cortex (PMv) in semantic processing.

    Science.gov (United States)

    Cattaneo, Zaira; Devlin, Joseph T; Salvini, Francesca; Vecchi, Tomaso; Silvanto, Juha

    2010-02-01

    The left ventral premotor cortex (PMv) is preferentially activated by exemplars of tools, suggestive of category specificity in this region. Here we used state-dependent transcranial magnetic stimulation (TMS) to investigate the causal role of such category-specific neuronal representations in the encoding of tool words. Priming to a category name (either "Tool" or "Animal") was used with the objective of modulating the initial activation state of this region prior to application of TMS and the presentation of the target stimulus. When the target word was an exemplar of the "Tool" category, the effects of TMS applied over PMv (but not PMd) interacted with priming history by facilitating reaction times on incongruent trials while not affecting congruent trials. This congruency/TMS interaction implies that the "Tool" and "Animal" primes had a differential effect on the initial activation state of the left PMv and implies that this region is one neural locus of category-specific behavioral priming for the "Tool" category. TMS applied over PMv had no behavioral effect when the target stimulus was an exemplar of the "Animal" category, regardless of whether the target word was congruent or incongruent with the prime. That TMS applied over the left PMv interacted with a priming effect that extended from the category name ("Tool") to exemplars of that category suggests that this region contains neuronal representation associated with a specific semantic category. Our results also demonstrate that the state-dependent effects obtained in the combination of visual priming and TMS are useful in the study of higher-level cognitive functions. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  12. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  13. Dysconnection of right parietal and frontal cortex in neglect syndrome

    DEFF Research Database (Denmark)

    Dietz, Martin; Nielsen, Jørgen Feldbæk; Roepstorff, Andreas

    2017-01-01

    network, rather than a disruption of computation in any particular brain region. To test this hypothesis, we used Bayesian analysis of effective connectivity based on electroencephalographic recordings in patients with left-sided neglect after a right-hemisphere lesion. While age-matched healthy controls...

  14. Khat distorts the prefrontal cortex histology and function of adult ...

    African Journals Online (AJOL)

    Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive ...

  15. A boost of confidence: The role of the ventromedial prefrontal cortex in memory, decision-making, and schemas.

    Science.gov (United States)

    Hebscher, Melissa; Gilboa, Asaf

    2016-09-01

    The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process ("feeling of rightness"; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions

  16. Rostro-Caudal Organization of Connectivity between Cingulate Motor Areas and Lateral Frontal Regions

    Directory of Open Access Journals (Sweden)

    Kep Kee Loh

    2018-01-01

    Full Text Available According to contemporary views, the lateral frontal cortex is organized along a rostro-caudal functional axis with increasingly complex cognitive/behavioral control implemented rostrally, and increasingly detailed motor control implemented caudally. Whether the medial frontal cortex follows the same organization remains to be elucidated. To address this issue, the functional connectivity of the 3 cingulate motor areas (CMAs in the human brain with the lateral frontal cortex was investigated. First, the CMAs and their representations of hand, tongue, and eye movements were mapped via task-related functional magnetic resonance imaging (fMRI. Second, using resting-state fMRI, their functional connectivity with lateral prefrontal and lateral motor cortical regions of interest (ROIs were examined. Importantly, the above analyses were conducted at the single-subject level to account for variability in individual cingulate morphology. The results demonstrated a rostro-caudal functional organization of the CMAs in the human brain that parallels that in the lateral frontal cortex: the rostral CMA has stronger functional connectivity with prefrontal regions and weaker connectivity with motor regions; conversely, the more caudal CMAs have weaker prefrontal and stronger motor connectivity. Connectivity patterns of the hand, tongue and eye representations within the CMAs are consistent with that of their parent CMAs. The parallel rostral-to-caudal functional organization observed in the medial and lateral frontal cortex could likely contribute to different hierarchies of cognitive-motor control.

  17. Frontal mucocele with intracranial extension causing frontal lobe syndrome.

    Science.gov (United States)

    Weidmayer, Sara

    2015-06-01

    Mucoceles are mucus-containing cysts that form in paranasal sinuses; although mucoceles themselves are benign, this case report highlights the extensive damage they can cause as their expansion may lead to bony erosion and extension of the mucocele into the orbit and cranium; it also presents a rarely reported instance of frontal sinus mucocele leading to frontal lobe syndrome. A thorough discussion and review of mucoceles is included. A 68-year-old white man presented with intermittent diplopia and a pressure sensation in the right eye. He had a history of chronic sinusitis and had had endoscopic sinus surgery 5 years prior. A maxillofacial computed tomography scan revealed a large right frontal sinus mucocele, which had caused erosion along the medial wall of the right orbit and the outer and inner tables of the right frontal sinus. The mucocele had protruded both into the right orbit and intracranially, causing mass effect on the frontal lobe, which led to frontal lobe syndrome. The patient was successfully treated with endoscopic right ethmoidectomy, radial frontal sinusotomy, marsupialization of the mucocele, and transcutaneous irrigation. Paranasal sinus mucoceles may expand and lead to bony erosion and can become very invasive in surrounding structures such as the orbit and cranium. This case not only exhibits a very rare presentation of frontal sinus mucocele with intracranial extension and frontal lobe mass effect causing a frontal lobe syndrome but also demonstrates many of the ocular and visual complications commonly associated with paranasal sinus mucoceles. Early identification and surgical intervention is vital for preventing and reducing morbidity associated with invasive mucoceles, and the patient must be followed regularly to monitor for recurrence.

  18. Postsynaptic TrkB signaling has distinct roles in spine maintenance in adult visual cortex and hippocampus

    NARCIS (Netherlands)

    Chkravarthy, S.; Saiepour, M.H.; Bence, M.; Perry, S.; Hartman, R.; Couey, J.J.; Mansvelder, H.D.; Levelt, C.N.

    2006-01-01

    In adult primary visual cortex (V1), dendritic spines are more persistent than during development. Brain-derived neurotrophic factor (BDNF) increases synaptic strength, and its levels rise during cortical development. We therefore asked whether postsynaptic BDNF signaling through its receptor TrkB

  19. The Role of the Orbitofrontal Cortex in Normally Developing Compulsive-Like Behaviors and Obsessive-Compulsive Disorder

    Science.gov (United States)

    Evans, David W.; Lewis, Marc D.; Iobst, Emily

    2004-01-01

    Mounting evidence concerning obsessive-compulsive disorders points to abnormal functioning of the orbitofrontal cortices. First, patients with obsessive-compulsive disorder (OCD) perform poorly on tasks that rely on response suppression/motor inhibition functions mediated by the orbitofrontal cortex relative to both normal and clinical controls.…

  20. Role of the Ventral Medial Prefrontal Cortex in Mediating Behavioral Control-Induced Reduction of Later Conditioned Fear

    Science.gov (United States)

    Baratta, Michael V.; Lucero, Thomas R.; Amat, Jose; Watkins, Linda R.; Maier, Steven F.

    2008-01-01

    A prior experience of behavioral control over a stressor interferes with subsequent Pavlovian fear conditioning, and this effect is dependent on the activation of the ventral medial prefrontal cortex (mPFCv) at the time of the initial experience with control. It is unknown whether mPFCv activity is necessary during fear learning and/or testing for…

  1. The role of catecholamine innervation in the medial prefrontal cortex on the regulation of body weight and food intake.

    Science.gov (United States)

    Gálosi, Rita; Hajnal, Andras; Petykó, Zoltán; Hartmann, Géza; Karádi, Zoltán; Lénárd, László

    2015-06-01

    Effects of 6-hydroxydopamine (6-OHDA) lesions in the medial prefrontal cortex with or without protection of norepinephrine (NE) fibers were examined on basic regulatory processes of feeding. Daily body weight, food and water intake were measured. Locomotor activity, ingestion after food or water deprivation, and preference for 5% and 10% glucose solution were examined. Dopamine (DA) and NE content, as well as, tyrosine hydroxylase immunoreactivity were assessed to confirm the neurotoxic effect of treatments. 6-OHDA lesions of the medial prefrontal cortex with or without NE fiber protection resulted in body weight loss. Diminished habituation in open field tests, i.e. a persistently high motor activity, was also observed. Application of 6-OHDA with NE fiber protection led to increased food consumption following food-deprivation and to enhanced glucose preference. Enhanced intake of 10% over 5% glucose solution was also detected. 6-OHDA lesion resulted in a decrease to 20% of NE tissue concentration and only to 75% of DA concentration. In case of lesion with NE protection the NE content decreased to 69% and DA level to 51% with significant loss of tyrosine hydroxylase positive fibers in the deeper layers of the medial prefrontal cortex. DA depletion in the medial prefrontal cortex resulted in increased behavioral responsiveness to hunger and glucose, as well as, to open field environment. Pronounced lesion of NE terminals caused increased reaction to the environment in open field but not to hunger or glucose solution. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Tell it to a child! A brain stimulation study of the role of left inferior frontal gyrus in emotion regulation during storytelling.

    Science.gov (United States)

    Urgesi, Cosimo; Mattiassi, Alan D A; Buiatti, Tania; Marini, Andrea

    2016-08-01

    In everyday life we need to continuously regulate our emotional responses according to their social context. Strategies of emotion regulation allow individuals to control time, intensity, nature and expression of emotional responses to environmental stimuli. The left inferior frontal gyrus (LIFG) is involved in the cognitive control of the selection of semantic content. We hypothesized that it might also be involved in the regulation of emotional feelings and expressions. We applied continuous theta burst stimulation (cTBS) over LIFG or a control site before a newly-developed ecological regulation task that required participants to produce storytelling of pictures with negative or neutral valence to either a peer (unregulated condition) or a child (regulated condition). Linguistic, expressive, and physiological responses were analyzed in order to assess the effects of LIFG-cTBS on emotion regulation. Results showed that the emotion regulation context modulated the emotional content of narrative productions, but not the physiologic orienting response or the early expressive behavior to negative stimuli. Furthermore, LIFG-cTBS disrupted the text-level structuring of negative picture storytelling and the early cardiac and muscular response to negative pictures; however, it did not affect the contextual emotional regulation of storytelling. These results may suggest that LIFG is involved in the initial detection of the affective arousal of emotional stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Frontal Midline Theta Oscillations during Mental Arithmetic: Effects of Stress

    Directory of Open Access Journals (Sweden)

    Matti eGärtner

    2015-04-01

    Full Text Available Complex cognitive tasks such as mental arithmetic heavily rely on intact, well-coordinated prefrontal cortex (PFC function. Converging evidence suggests that frontal midline theta (FMT oscillations play an important role during the execution of such PFC-dependent tasks. Additionally, it is well-established that acute stress impairs PFC function, and recent evidence suggests that FMT is decreased under stress. In this EEG study, we investigated FMT oscillations during a mental arithmetic task that was carried out in a stressful and a neutral control condition. Our results show late-onset, sustained FMT increases during mental arithmetic. In the neutral condition FMT started to increase earlier than in the stress condition. Direct comparison of the conditions quantified this difference by showing stronger FMT increases in the neutral condition in an early time window. Between-subject correlation analysis showed that attenuated FMT under stress was related to slowed reaction times. Our results suggest that FMT is associated with stimulus independent mental processes during the natural and complex PFC-dependent task of mental arithmetic, and is a possible marker for intact PFC function that is disrupted under stress.

  4. Frontal midline theta oscillations during mental arithmetic: effects of stress.

    Science.gov (United States)

    Gärtner, Matti; Grimm, Simone; Bajbouj, Malek

    2015-01-01

    Complex cognitive tasks such as mental arithmetic heavily rely on intact, well-coordinated prefrontal cortex (PFC) function. Converging evidence suggests that frontal midline theta (FMT) oscillations play an important role during the execution of such PFC-dependent tasks. Additionally, it is well-established that acute stress impairs PFC function, and recent evidence suggests that FMT is decreased under stress. In this EEG study, we investigated FMT oscillations during a mental arithmetic task that was carried out in a stressful and a neutral control condition. Our results show late-onset, sustained FMT increases during mental arithmetic. In the neutral condition FMT started to increase earlier than in the stress condition. Direct comparison of the conditions quantified this difference by showing stronger FMT increases in the neutral condition in an early time window. Between-subject correlation analysis showed that attenuated FMT under stress was related to slowed reaction times. Our results suggest that FMT is associated with stimulus independent mental processes during the natural and complex PFC-dependent task of mental arithmetic, and is a possible marker for intact PFC function that is disrupted under stress.

  5. Prospective memory and frontal lobe function.

    Science.gov (United States)

    Neulinger, Kerryn; Oram, Joanne; Tinson, Helen; O'Gorman, John; Shum, David H K

    2016-01-01

    The study sought to examine the role of frontal lobe functioning in focal prospective memory (PM) performance and its relation to PM deficit in older adults. PM and working memory (WM) differences were studied in younger aged (n = 21), older aged (n = 20), and frontal injury (n = 14) groups. An event-based focal PM task was employed and three measures of WM were administered. The younger aged group differed from the other two groups in showing significantly higher scores on PM and on one of the WM measures, but there were no differences at a statistically significant level between the older aged group and the frontal injury groups on any of the memory measures. There were, however, some differences in correlations with a WM measure between groups. It is concluded that there are similarities and differences in the deficits in PM between older adults and patients with frontal lobe injury on focal as well as nonfocal PM tasks.

  6. NEURAL CORRELATES FOR APATHY: FRONTAL - PREFRONTAL AND PARIETAL CORTICAL - SUBCORTICAL CIRCUITS

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2016-12-01

    Full Text Available Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional invovlement; it is an important and heavy-burden clinical condition which strongly impacts in every day life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC and basal ganglia; emotional affective apathy may be related to the orbitomedial PFC and ventral striatum; cognitive apathy may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of autoactivation may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to grey matter atrophy in the anterior cingulate (ACC and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies and a reduced speedness in action decsion, major resposnible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control.We will discuss the importance of these circuits in different pathologies

  7. Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

    Science.gov (United States)

    Moretti, Rita; Signori, Riccardo

    2016-01-01

    Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; “emotional affective” apathy may be related to the orbitomedial PFC and ventral striatum; “cognitive apathy” may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of “autoactivation” may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies

  8. Origami by frontal photopolymerization.

    Science.gov (United States)

    Zhao, Zeang; Wu, Jiangtao; Mu, Xiaoming; Chen, Haosen; Qi, H Jerry; Fang, Daining

    2017-04-01

    Origami structures are of great interest in microelectronics, soft actuators, mechanical metamaterials, and biomedical devices. Current methods of fabricating origami structures still have several limitations, such as complex material systems or tedious processing steps. We present a simple approach for creating three-dimensional (3D) origami structures by the frontal photopolymerization method, which can be easily implemented by using a commercial projector. The concept of our method is based on the volume shrinkage during photopolymerization. By adding photoabsorbers into the polymer resin, an attenuated light field is created and leads to a nonuniform curing along the thickness direction. The layer directly exposed to light cures faster than the next layer; this nonuniform curing degree leads to nonuniform curing-induced volume shrinkage. This further introduces a nonuniform stress field, which drives the film to bend toward the newly formed side. The degree of bending can be controlled by adjusting the gray scale and the irradiation time, an easy approach for creating origami structures. The behavior is examined both experimentally and theoretically. Two methods are also proposed to create different types of 3D origami structures.

  9. Frontal-subcortical volumetric deficits in single episode, medication-naïve depressed patients and the effects of 8 weeks fluoxetine treatment: a VBM-DARTEL study.

    Directory of Open Access Journals (Sweden)

    Lingtao Kong

    Full Text Available BACKGROUND: Convergent studies suggest that morphological abnormalities of frontal-subcortical circuits which involved with emotional and cognitive processing may contribute to the pathophysiology of major depressive disorder (MDD. Antidepressant treatment which has been reported to reverse the functional abnormalities of frontal-subcortical circuits in MDD may have treating effects to related brain morphological abnormalities. In this study, we used voxel-based morphometry method to investigate whole brain structural abnormalities in single episode, medication-naïve MDD patients. Furthermore, we investigated the effects of an 8 weeks pharmacotherapy with fluoxetine. METHODS: 28 single episode, medication-naïve MDD participants and 28 healthy controls (HC acquired the baseline high-resolution structural magnetic resonance imaging (sMRI scan. 24 MDD participants acquired a follow-up sMRI scan after 8 weeks antidepressant treatment. Gray matter volumetric (GMV difference between groups was examined. RESULTS: Medication-naïve MDD had significantly decreased GMV in the right dorsolateral prefrontal cortex and left middle frontal gyrus as well as increased GMV in the left thalamus and right insula compared to HC (P<0.05, corrected. Moreover, treated MDD had significantly increased GMV in the left middle frontal gyrus and right orbitofrontal cortex compared to HC (P<0.05, corrected. No difference on GMV was detected between medication-naïve MDD group and treated MDD group. CONCLUSIONS: This study of single episode, medication-naïve MDD subjects demonstrated structural abnormalities of frontal-subcortical circuitsin the early stage of MDD and the effects of 8 weeks successful antidepressant treatment, suggesting these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.

  10. Reduced frontal cortical thickness and increased caudate volume within fronto-striatal circuits in young adult smokers.

    Science.gov (United States)

    Li, Yangding; Yuan, Kai; Cai, Chenxi; Feng, Dan; Yin, Junsen; Bi, Yanzhi; Shi, Sha; Yu, Dahua; Jin, Chenwang; von Deneen, Karen M; Qin, Wei; Tian, Jie

    2015-06-01

    Smoking during early adulthood results in neurophysiological and brain structural changes that may promote nicotine dependence later in life. Previous studies have revealed the important roles of fronto-striatal circuits in the pathology of nicotine dependence; however, few studies have focused on both cortical thickness and subcortical striatal volume differences between young adult smokers and nonsmokers. Twenty-seven young male adult smokers and 22 age-, education- and gender-matched nonsmokers were recruited in the present study. The cortical thickness and striatal volume differences of young adult smokers and age-matched nonsmokers were investigated in the present study and then correlated with pack-years and Fagerström Test for Nicotine Dependence (FTND). The following results were obtained: (1) young adult smokers showed significant cortical thinning in the frontal cortex (left caudal anterior cingulate cortex (ACC), right lateral orbitofrontal cortex (OFC)), left insula, left middle temporal gyrus, right inferior parietal lobule, and right parahippocampus; (2) in regards to subcortical striatal volume, the volume of the right caudate was larger in young adult smokers than nonsmokers; and (3) the cortical thickness of the right dorsolateral prefrontal cortex (DLPFC) and OFC were associated with nicotine dependence severity (FTND) and cumulative amount of nicotine intake (pack-years) in smokers, respectively. This study revealed reduced frontal cortical thickness and increased caudate volume in the fronto-striatal circuits in young adult smokers compared to nonsmokers. These deficits suggest an imbalance between cognitive control (reduced protection factors) and reward drive behaviours (increased risk factors) associated with nicotine addiction and relapse. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Frontal activation and connectivity using near-infrared spectroscopy: verbal fluency language study.

    Science.gov (United States)

    Chaudhary, Ujwal; Hall, Michael; DeCerce, Joe; Rey, Gustavo; Godavarty, Anuradha

    2011-02-28

    Near infrared spectroscopy (NIRS) is an optical technique with high temporal resolution and reasonably good spatial resolution, which allows non invasive measurement of the blood oxygenation of tissue. The current work is focused in assessing and correlating brain activation, connectivity and cortical lateralization of the frontal cortex in response to language-based stimuli, using NIRS. Experimental studies were performed on 15 normal right-handed adults, wherein the participants were presented with a verbal fluency task. The hemodynamic responses in the pre- and anterior frontal cortex were assessed in response to a Word generation task in comparison to the baseline random Jaw movement and Rest conditions. The functional connectivity analysis was performed using zero-order correlations and the cortical lateralization was evaluated as well. An increase in oxy- and a decrease in deoxy-hemoglobin were observed during verbal fluency task in the frontal cortex. Unlike in the pre-frontal cortex, the hemodynamic response in the anterior frontal during verbal fluency task was not significantly different from that during random Jaw movement. Bilateral activation and symmetrical connectivity were observed in the pre-frontal cortex, independent of the stimuli presented. A left cortical dominance and asymmetry connectivity was observed in the anterior frontal during the verbal fluency task. The work is focused to target the pediatric epileptic populations in the future, where understanding the brain functionality (activation, connectivity, and dominance) in response to language is essential as a part of the pre-surgical evaluation in a clinical environment. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. The Role of Nicotinic Acetylcholine Receptors in the Medial Prefrontal Cortex and Hippocampus in Trace Fear Conditioning

    OpenAIRE

    Raybuck, J. D.; Gould, T. J.

    2010-01-01

    Acute nicotine enhances multiple types of learning including trace fear conditioning but the underlying neural substrates of these effects are not well understood. Trace fear conditioning critically involves the medial prefrontal cortex and hippocampus, which both express nicotinic acetylcholine receptors (nAChRs). Therefore, nicotine could act in either or both areas to enhance trace fear conditioning. To identify the underlying neural areas and nAChR subtypes, we examined the effects of inf...

  13. Top-down modulation from inferior frontal junction to FEFs and intraparietal sulcus during short-term memory for visual features.

    Science.gov (United States)

    Sneve, Markus H; Magnussen, Svein; Alnæs, Dag; Endestad, Tor; D'Esposito, Mark

    2013-11-01

    Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166-178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top-down biasing of sensory cortex.

  14. Temporary Frontal Paralysis Secondary to Blunt Trauma Frontal Sinus Fracture

    Science.gov (United States)

    Hamilton, Stefan; Hearn, Matthew; Kherani, Safeena; Macdonald, Kristian I.

    2017-01-01

    Frontal sinus fractures (FSF) are relatively uncommon and can be challenging for trauma surgeons to manage. Patients with FSF typically present with facial swelling, pain, and nasofrontal ecchymosis. Here we present a rare case of a patient with FSF and anterior table fracture where the main presenting symptom was bilateral frontal paralysis. We outline our management strategy and review the current literature in regard to management of FSF. PMID:28573060

  15. CEREBRAL CORTEX DAMAGE INDUCED BY ACUTE ORAL ...

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... Keywords: Brain, cerebral cortex, alcohol, Wistar rats, oxidative stress. INTRODUCTION. The prefrontal cortex is ... damage, memory loss, sleep disorders and psychosis, with or without ..... and emotional consequences of binge drinking: Role of amygdala and prefrontal cortex. Philos Trans R Soc Lond Biol ...

  16. Frontoparietal cortex mediates perceptual transitions in bistable perception.

    Science.gov (United States)

    Weilnhammer, Veith A; Ludwig, Karin; Hesselmann, Guido; Sterzer, Philipp

    2013-10-02

    During bistable vision, perception oscillates between two mutually exclusive percepts despite constant sensory input. Greater BOLD responses in frontoparietal cortex have been shown to be associated with endogenous perceptual transitions compared with "replay" transitions designed to closely match bistability in both perceptual quality and timing. It has remained controversial, however, whether this enhanced activity reflects causal influences of these regions on processing at the sensory level or, alternatively, an effect of stimulus differences that result in, for example, longer durations of perceptual transitions in bistable perception compared with replay conditions. Using a rotating Lissajous figure in an fMRI experiment on 15 human participants, we controlled for potential confounds of differences in transition duration and confirmed previous findings of greater activity in frontoparietal areas for transitions during bistable perception. In addition, we applied dynamic causal modeling to identify the neural model that best explains the observed BOLD signals in terms of effective connectivity. We found that enhanced activity for perceptual transitions is associated with a modulation of top-down connectivity from frontal to visual cortex, thus arguing for a crucial role of frontoparietal cortex in perceptual transitions during bistable perception.

  17. Maintenance and manipulation of somatosensory information in ventrolateral prefrontal cortex.

    Science.gov (United States)

    Spitzer, Bernhard; Goltz, Dominique; Wacker, Evelin; Auksztulewicz, Ryszard; Blankenburg, Felix

    2014-05-01

    Neuroimaging studies of working memory (WM) suggest that prefrontal cortex may assist sustained maintenance, but also internal manipulation, of stimulus representations in lower-level areas. A different line of research in the somatosensory domain indicates that neuronal activity in ventrolateral prefrontal cortex (VLPFC) may also represent specific memory contents in itself, however leaving open to what extent top-down control on lower-level areas is exerted, or how internal manipulation processes are implemented. We used functional imaging and connectivity analysis to study static maintenance and internal manipulation of tactile working memory contents after physically identical stimulation conditions, in human subjects. While both tasks recruited similar subareas in the inferior frontal gyrus (IFG) in VLPFC, static maintenance of the tactile information was additionally characterized by increased functional coupling between IFG and primary somatosensory cortex. Independently, during internal manipulation, a quantitative representation of the task-relevant information was evident in IFG itself, even in the absence of physical stimulation. Together, these findings demonstrate the functional diversity of activity within VLPFC according to different working memory demands, and underline the role of IFG as a core region in sensory WM processing. Copyright © 2013 Wiley Periodicals, Inc.

  18. Distinct frontal lobe morphology in girls and boys with ADHD.

    Science.gov (United States)

    Dirlikov, Benjamin; Shiels Rosch, Keri; Crocetti, Deana; Denckla, Martha B; Mahone, E Mark; Mostofsky, Stewart H

    2015-01-01

    This study investigated whether frontal lobe cortical morphology differs for boys and girls with ADHD (ages 8-12 years) in comparison to typically developing (TD) peers. Participants included 226 children between the ages of 8-12 including 93 children with ADHD (29 girls) and 133 TD children (42 girls) for which 3T MPRAGE MRI scans were obtained. A fully automated frontal lobe atlas was used to generate functionally distinct frontal subdivisions, with surface area (SA) and cortical thickness (CT) assessed in each region. Analyses focused on overall diagnostic differences as well as examinations of the effect of diagnosis within boys and girls. Girls, but not boys, with ADHD showed overall reductions in total prefrontal cortex (PFC) SA. Localization revealed that girls showed widely distributed reductions in the bilateral dorsolateral PFC, left inferior lateral PFC, right medial PFC, right orbitofrontal cortex, and left anterior cingulate; and boys showed reduced SA only in the right anterior cingulate and left medial PFC. In contrast, boys, but not girls, with ADHD showed overall reductions in total premotor cortex (PMC) SA. Further localization revealed that in boys, premotor reductions were observed in bilateral lateral PMC regions; and in girls reductions were observed in bilateral supplementary motor complex. In line with diagnostic group differences, PMC and PFC SAs were inversely correlated with symptom severity in both girls and boys with ADHD. These results elucidate sex-based differences in cortical morphology of functional subdivisions of the frontal lobe and provide additional evidence of associations among SA and symptom severity in children with ADHD.

  19. Frontal lobe function in temporal lobe epilepsy

    Science.gov (United States)

    Stretton, J.; Thompson, P.J.

    2012-01-01

    Summary Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further. PMID:22100147

  20. Finding prefrontal cortex in the rat.

    Science.gov (United States)

    Leonard, Christiana M

    2016-08-15

    The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B

  1. Differences in the neural correlates of frontal lobe tests.

    Science.gov (United States)

    Matsuoka, Teruyuki; Kato, Yuka; Imai, Ayu; Fujimoto, Hiroshi; Shibata, Keisuke; Nakamura, Kaeko; Yamada, Kei; Narumoto, Jin

    2018-01-01

    The Executive Interview (EXIT25), the executive clock-drawing task (CLOX1), and the Frontal Assessment Battery (FAB) are used to assess executive function at the bedside. These tests assess distinct psychometric properties. The aim of this study was to examine differences in the neural correlates of the EXIT25, CLOX1, and FAB based on magnetic resonance imaging. Fifty-eight subjects (30 with Alzheimer's disease, 10 with mild cognitive impairment, and 18 healthy controls) participated in this study. Multiple regression analyses were performed to examine the brain regions correlated with the EXIT25, CLOX1, and FAB scores. Age, gender, and years of education were included as covariates. Statistical thresholds were set to uncorrected P-values of 0.001 at the voxel level and 0.05 at the cluster level. The EXIT25 score correlated inversely with the regional grey matter volume in the left lateral frontal lobe (Brodmann areas 6, 9, 44, and 45). The CLOX1 score correlated positively with the regional grey matter volume in the right orbitofrontal cortex (Brodmann area 11) and the left supramarginal gyrus (Brodmann area 40). The FAB score correlated positively with the regional grey matter volume in the right precentral gyrus (Brodmann area 6). The left lateral frontal lobe (Brodmann area 9) and the right lateral frontal lobe (Brodmann area 46) were identified as common brain regions that showed association with EXIT25, CLOX1, and FAB based only a voxel-level threshold. The results of this study suggest that the EXIT25, CLOX1, and FAB may be associated with the distinct neural correlates of the frontal cortex. © 2018 Japanese Psychogeriatric Society.

  2. Neural Tuning to Low-Level Features of Speech throughout the Perisylvian Cortex.

    Science.gov (United States)

    Berezutskaya, Julia; Freudenburg, Zachary V; Güçlü, Umut; van Gerven, Marcel A J; Ramsey, Nick F

    2017-08-16

    perisylvian cortex and potentially contribute to the emergence of "coarse" speech representations in inferior frontal gyrus typically associated with high-level language processing. These findings add to the previous work on auditory processing and underline a distinctive role of inferior frontal gyrus in natural speech comprehension. Copyright © 2017 the authors 0270-6474/17/377906-15$15.00/0.

  3. Opioid-receptor (OR) signaling cascades in rat cerebral cortex and model cell lines: the role of plasma membrane structure

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Brejchová, Jana; Vošahlíková, Miroslava; Kagan, Dmytro; Dlouhá, Kateřina; Sýkora, Jan; Merta, Ladislav; Drastichová, Z.; Novotný, J.; Ostašov, Pavel; Roubalová, Lenka; Parenti, M.; Hof, Martin; Svoboda, Petr

    2014-01-01

    Roč. 63, Suppl.1 (2014), S165-S176 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : GPCR * morphine * mu-OR, delta-OR and kappa-OR * rat brain cortex * adenylyl cyclase I and II * proteomic analysis Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 1.293, year: 2014

  4. Altered basal ganglia-cortical functional connections in frontal lobe epilepsy: A resting-state fMRI study.

    Science.gov (United States)

    Dong, Li; Wang, Pu; Peng, Rui; Jiang, Sisi; Klugah-Brown, Benjamin; Luo, Cheng; Yao, Dezhong

    2016-12-01

    The purpose of this study was to investigate alterations of basal ganglia-cortical functional connections in patients with frontal lobe epilepsy (FLE). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from 19 FLE patients and 19 age- and gender-matched healthy controls. Functional connectivity (FC) analysis was used to assess the functional connections between basal ganglia and cerebral cortex. Regions of interest, including the left/right caudate, putamen, pallidum and thalamus, were selected as the seeds. Two sample t-test was used to determine the difference between patients and controls, while controlling the age, gender and head motions. Compared with controls, FLE patients demonstrated increased FCs between basal ganglia and regions including the right fusiform gyrus, the bilateral cingulate gyrus, the precuneus and anterior cingulate gyrus. Reduced FCs were mainly located in a range of brain regions including the bilateral middle occipital gyrus, the ventral frontal lobe, the right putamen, the left fusiform gyrus and right rolandic operculum. In addition, the relationships between basal ganglia-cingulate connections and durations of epilepsy were also found. The alterations of functional integrity within the basal ganglia, as well as its connections to limbic and ventral frontal areas, indicate the important roles of the basal ganglia-cortical functional connections in FLE, and provide new insights in the pathophysiological mechanism of FLE. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Effects of prefrontal cortex damage on emotion understanding: EEG and behavioural evidence.

    Science.gov (United States)

    Perry, Anat; Saunders, Samantha N; Stiso, Jennifer; Dewar, Callum; Lubell, Jamie; Meling, Torstein R; Solbakk, Anne-Kristin; Endestad, Tor; Knight, Robert T

    2017-04-01

    Humans are highly social beings that interact with each other on a daily basis. In these complex interactions, we get along by being able to identify others' actions and infer their intentions, thoughts and feelings. One of the major theories accounting for this critical ability assumes that the understanding of social signals is based on a primordial tendency to simulate observed actions by activating a mirror neuron system. If mirror neuron regions are important for action and emotion recognition, damage to regions in this network should lead to deficits in these domains. In the current behavioural and EEG study, we focused on the lateral prefrontal cortex including dorsal and ventral prefrontal cortex and utilized a series of task paradigms, each measuring a different aspect of recognizing others' actions or emotions from body cues. We examined 17 patients with lesions including (n = 8) or not including (n = 9) the inferior frontal gyrus, a core mirror neuron system region, and compared their performance to matched healthy control subjects (n = 18), in behavioural tasks and in an EEG observation-execution task measuring mu suppression. Our results provide support for the role of the lateral prefrontal cortex in understanding others' emotions, by showing that even unilateral lesions result in deficits in both accuracy and reaction time in tasks involving the recognition of others' emotions. In tasks involving the recognition of actions, patients showed a general increase in reaction time, but not a reduction in accuracy. Deficits in emotion recognition can be seen by either direct damage to the inferior frontal gyrus, or via damage to dorsal lateral prefrontal cortex regions, resulting in deteriorated performance and less EEG mu suppression over sensorimotor 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.

  6. Evaluative vs. trait representation in intergroup social judgments: distinct roles of anterior temporal lobe and prefrontal cortex.

    Science.gov (United States)

    Gilbert, Sam J; Swencionis, Jillian K; Amodio, David M

    2012-12-01

    When interacting with someone from another social group, one's responses may be influenced by both stereotypes and evaluations. Given behavioral results suggesting that stereotypes and evaluative associations operate independently, we used fMRI to test whether these biases are mediated by distinct brain systems. White participants viewed pairs of Black or White faces and judged them based on an evaluation (who would you befriend?) or a stereotype-relevant trait (who is more likely to enjoy athletic activities?). Multi-voxel pattern analysis revealed that a predominantly occipital network represented race in a context-invariant manner. However, lateral orbitofrontal cortex preferentially represented race during friendship judgments, whereas anterior medial prefrontal cortex preferentially represented race during trait judgments. Furthermore, representation of race in left temporal pole correlated with a behavioral measure of evaluative bias during friendship judgments and, independently, a measure of stereotyping during trait judgments. Whereas early sensory regions represent race in an apparently invariant manner, representations in higher-level regions are multi-componential and context-dependent. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Non-primary motor areas in the human frontal lobe are connected directly to hand muscles.

    Science.gov (United States)

    Teitti, S; Määttä, S; Säisänen, L; Könönen, M; Vanninen, R; Hannula, H; Mervaala, E; Karhu, J

    2008-04-15

    Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

  8. [Effects of blokade of the dopaminergic D1/D2 receptors on the single and network neuronal activity in the frontal and visual cortices and behavior of cats].

    Science.gov (United States)

    Kuleshova, E P; Zaleshin, A V; Sidorina, V V; Merzhanova, G Kh

    2010-01-01

    The results obtained at the levels of single and network neuronal activity in the frontal and visual cortices of cats with different types of behavior revealed features of activity of these structures in normal conditions and after local introductions of antagonists of DI/D2 receptors (SCH23390 and raclopride) into the n. accumbens and frontal cortex. Under the influence of the antagonists, long-latency reactions were characterized by a significant increase in the average frequency of neuronal activity in the frontal cortex, whereas in the visual cortex the average frequency decreased as compared to norm. At the same time, the network activity of the same neurons in the frontal cortex did not change but weakened in the visual cortex, which was expressed in a reduction of the number of neuronal interactions within the visual cortex and between the neurons of the frontal and visual cortices. Normally, during the long-latency conditioned reactions, the average frequency of single neuronal activity and the rate of neuronal interactions in the structures under study were significantly higher as compared to the loss of conditioned reactions. Administration of the dopamine antagonists did not change these features. The results suggest different dopamine modulations of the network activity of the cortical zones under study during the conditioned performance, which is expressed in responsiveness of the cortical projection of a trigger signal (the visual cortex) and visual-frontal networks generated in the course of training.

  9. The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: behavioral, biochemical and immunocytochemical studies.

    Science.gov (United States)

    Lehner, Małgorzata; Taracha, Ewa; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Kołomańska, Paulina; Skórzewska, Anna; Maciejak, Piotr; Szyndler, Janusz; Bidziński, Andrzej; Płaźnik, Adam

    2008-10-10

    In this study we have explored differences in animal reactivity to conditioned aversive stimuli using the conditioned fear test (a contextual fear-freezing response), in rats subjected to the selective lesion of the prefrontal cortex serotonergic innervation, and differing in their response to the acute painful stimulation, a footshock (HS--high sensitivity rats, and LS--low sensitivity rats, selected arbitrarily according to their behavior in the 'flinch-jump' pre-test). Local administration of serotonergic neurotoxin (5,7-dihydroxytryptamine) to the dorsomedial part of the prefrontal cortex caused a very strong, structure and neurotransmitter selective depletion of serotonin concentration. In HS rats, the serotonergic lesion significantly disinhibited rat behavior controlled by fear, enhanced c-Fos expression in the dorsomedial prefrontal area, and increased the concentration of GABA in the basolateral amygdala, measured in vivo after the testing session of the conditioned fear test. The LS animals revealed an opposite pattern of behavioral and biochemical changes after serotonergic lesion: an increase in the duration of a freezing response, and expression of c-Fos in the basolateral and central nuclei of amygdala, and a lower GABA concentration in the basolateral amygdala. In control conditions, c-Fos expression did not differ in LS and HS, naïve, not conditioned and not exposed to the test cage animals. The present study adds more arguments for the controlling role of serotonergic innervation of the dorsomedial part of the prefrontal cortex in processing emotional input by other brain centers. Moreover, it provides experimental data, which may help to better explain the anatomical and biochemical basis of differences in individual reactivity to stressful stimulation, and, possibly, to anxiolytic drugs with serotonergic or GABAergic profiles of action.

  10. The role of ventromedial prefrontal cortex volume in the association of expressive suppression and externally oriented thinking.

    Science.gov (United States)

    Li, Xu; Lu, Jiamei; Li, Bingbing; Li, Haijiang; Jin, Li; Qiu, Jiang

    2017-11-01

    Studies have suggested that expressive suppression (ES) is linked to externally oriented thinking (EOT) through the ventromedial prefrontal cortex (vmPFC), and there are gender differences in their association. The present structural magnetic resonance imaging study was to investigate the neural bases of ES and EOT and their association in females versus males in a Chinese college sample. A total of 142 participants (83 females) were enrolled, and they completed the ES subscale of the Emotion Regulation Questionnaire, 20-item Toronto Alexithymia Scale, and anatomical scanning. Voxel-based morphometry, region of interest, and whole brain analyses with peak-level significance (family-wise error corrected at p design limited causal conclusions. The vmPFC may be the only neural base of ES and EOT and their association. In addition, these results were sex-specific. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The role of temporal predictability in the anticipatory biasing of sensory cortex during visuospatial shifts of attention.

    Science.gov (United States)

    Green, Jessica J; McDonald, John J

    2010-11-01

    The presentation of an attention-directing cue elicits a lateralized ERP deflection called the late directing attention positivity (LDAP) and lateralized changes in alpha-band elelctroencephalogram oscillations. Both of these electrophysiological responses have been independently linked to biasing of visual cortex in anticipation of an impending target. However, the LDAP is not always observed, and the link between the ERP and alpha-band modulations remains unclear. Here, we examined the effect of advance knowledge of the time of target onset on the ERP and alpha-band responses to cues. The LDAP was present only when the attention-directing cues accurately indicated the time of target appearance, whereas two sequential attention-related alpha-band modulations were observed regardless of the temporal information provided by the cues. Thus, alpha-band activity may be a more reliable index of pretarget biasing of visual cortical activity than lateralized ERP effects. Copyright © 2010 Society for Psychophysiological Research.

  12. Functional disconnection of frontal cortex and visual cortex in attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Mazaheri, A.; Coffey-Corina, S.; Mangun, G.R.; Bekker, E.M.; Berry, A.S.; Corbett, B.A.

    2010-01-01

    BACKGROUND: Current pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) suggest that impaired functional connectivity within brain attention networks may contribute to the disorder. In this electroencephalographic (EEG) study, we analyzed cross-frequency amplitude correlations

  13. The role of the dorsal Anterior Cingulate Cortex (dACC) in a cognitive and emotional counting Stroop task: Two cases.

    Science.gov (United States)

    To, Wing Ting; De Ridder, Dirk; Menovsky, Tomas; Hart, John; Vanneste, Sven

    2017-01-01

    The anterior cingulate cortex (ACC) has been implicated in both cognitive and emotional processing, with cognitive information proposed to be processed through the dorsal/caudal ACC and emotional information through the rostral/ventral ACC. The objective of this study is to investigate the role of the dorsal anterior cingulate cortex (dACC) in cognitive and emotional processing using a cognitive and emotional counting Stroop task in two patients in whom abnormalities in the dACC were identified and treated. Two patients performed the cognitive and emotional counting Stroop task before and after treatment to examine whether the dACC has a specific or more general processing function. We observed an overall improvement in the emotional, cognitive, and neutral trials of the counting Stroop task after the intervention, indicating that the dACC is not a subregion of the ACC that only contributes to a specific domain. This study reveals that the dACC is not just a subregion of the ACC that contributes to a specific cognitive function, but is rather part of a salience network that influences general brain functioning, influencing cognitive as well as emotional processing.

  14. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    Science.gov (United States)

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia. Copyright © 2015 the American Physiological Society.

  15. High density scalp EEG in frontal lobe epilepsy.

    Science.gov (United States)

    Feyissa, Anteneh M; Britton, Jeffrey W; Van Gompel, Jamie; Lagerlund, Terrance L; So, Elson; Wong-Kisiel, Lilly C; Cascino, Gregory C; Brinkman, Benjamin H; Nelson, Cindy L; Watson, Robert; Worrell, Gregory A

    2017-01-01

    Localization of seizures in frontal lobe epilepsy using the 10-20 system scalp EEG is often challenging because neocortical seizure can spread rapidly, significant muscle artifact, and the suboptimal spatial resolution for seizure generators involving mesial frontal lobe cortex. Our aim in this study was to determine the value of visual interpretation of 76 channel high density EEG (hdEEG) monitoring (10-10 system) in patients with suspected frontal lobe epilepsy, and to evaluate concordance with MRI, subtraction ictal SPECT co-registered to MRI (SISCOM), conventional EEG, and intracranial EEG (iEEG). We performed a retrospective cohort study of 14 consecutive patients who underwent hdEEG monitoring for suspected frontal lobe seizures. The gold standard for localization was considered to be iEEG. Concordance of hdEEG findings with MRI, subtraction ictal SPECT co-registered to MRI (SISCOM), conventional 10-20 EEG, and iEEG as well as correlation of hdEEG localization with surgical outcome were examined. hdEEG localization was concordant with iEEG in 12/14 and was superior to conventional EEG 3/14 (pfrontal epilepsy requiring localization of epileptogenic brain. hdEEG may assist in developing a hypothesis for iEEG monitoring and could potentially augment EEG source localization. Published by Elsevier B.V.

  16. Development of a neurofeedback protocol targeting the frontal pole using near-infrared spectroscopy.

    Science.gov (United States)

    Kinoshita, Akihide; Takizawa, Ryu; Yahata, Noriaki; Homae, Fumitaka; Hashimoto, Ryuichiro; Sakakibara, Eisuke; Kawasaki, Shingo; Nishimura, Yukika; Koike, Shinsuke; Kasai, Kiyoto

    2016-11-01

    Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex. We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant (n = 24) received either correct or incorrect (Sham) feedback from near-infrared spectroscopy signals, based on a crossover design. Under correct feedback conditions, significant activation was observed in the frontal pole cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals (P = 0.006). The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

  17. Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

    OpenAIRE

    Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

    2008-01-01

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic d...

  18. Short-term memory for space and time flexibly recruit complementary sensory-biased frontal lobe attention networks

    Science.gov (United States)

    Michalka, Samantha W.; Kong, Lingqiang; Rosen, Maya L.; Shinn-Cunningham, Barbara G.; Somers, David C.

    2015-01-01

    Summary The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex. PMID:26291168

  19. Short-Term Memory for Space and Time Flexibly Recruit Complementary Sensory-Biased Frontal Lobe Attention Networks.

    Science.gov (United States)

    Michalka, Samantha W; Kong, Lingqiang; Rosen, Maya L; Shinn-Cunningham, Barbara G; Somers, David C

    2015-08-19

    The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Global increase in task-related fronto-parietal activity after focal frontal lobe lesion.

    Science.gov (United States)

    Woolgar, Alexandra; Bor, Daniel; Duncan, John

    2013-09-01

    A critical question for neuropsychology is how complex brain networks react to damage. Here, we address this question for the well-known executive control or multiple-demand (MD) system, a fronto-parietal network showing increased activity with many different kinds of cognitive demand, including standard tests of fluid intelligence. Using fMRI, we ask how focal frontal lobe damage affects MD activity during a standard fluid intelligence task. Despite poor behavioral performance, frontal patients showed increased fronto-parietal activity relative to controls. The activation difference was not accounted for by difference in IQ. Moreover, rather than specific focus on perilesional or contralesional cortex, additional recruitment was distributed throughout the MD regions and surrounding cortex and included parietal MD regions distant from the injury. The data suggest that, following local frontal lobe damage, there is a global compensatory recruitment of an adaptive and integrated fronto-parietal network.

  1. The selective role of premotor cortex in speech perception: a contribution to phoneme judgements but not speech comprehension.

    Science.gov (United States)

    Krieger-Redwood, Katya; Gaskell, M Gareth; Lindsay, Shane; Jefferies, Elizabeth

    2013-12-01

    Several accounts of speech perception propose that the areas involved in producing language are also involved in perceiving it. In line with this view, neuroimaging studies show activation of premotor cortex (PMC) during phoneme judgment tasks; however, there is debate about whether speech perception necessarily involves motor processes, across all task contexts, or whether the contribution of PMC is restricted to tasks requiring explicit phoneme awareness. Some aspects of speech processing, such as mapping sounds onto meaning, may proceed without the involvement of motor speech areas if PMC specifically contributes to the manipulation and categorical perception of phonemes. We applied TMS to three sites-PMC, posterior superior temporal gyrus, and occipital pole-and for the first time within the TMS literature, directly contrasted two speech perception tasks that required explicit phoneme decisions and mapping of speech sounds onto semantic categories, respectively. TMS to PMC disrupted explicit phonological judgments but not access to meaning for the same speech stimuli. TMS to two further sites confirmed that this pattern was site specific and did not reflect a generic difference in the susceptibility of our experimental tasks to TMS: stimulation of pSTG, a site involved in auditory processing, disrupted performance in both language tasks, whereas stimulation of occipital pole had no effect on performance in either task. These findings demonstrate that, although PMC is important for explicit phonological judgments, crucially, PMC is not necessary for mapping speech onto meanings.

  2. Dopamine D1 receptor stimulation modulates the formation and retrieval of novel object recognition memory: Role of the prelimbic cortex.

    Science.gov (United States)

    Pezze, Marie A; Marshall, Hayley J; Fone, Kevin C F; Cassaday, Helen J

    2015-11-01

    Previous studies have shown that dopamine D1 receptor antagonists impair novel object recognition memory but the effects of dopamine D1 receptor stimulation remain to be determined. This study investigated the effects of the selective dopamine D1 receptor agonist SKF81297 on acquisition and retrieval in the novel object recognition task in male Wistar rats. SKF81297 (0.4 and 0.8 mg/kg s.c.) given 15 min before the sampling phase impaired novel object recognition evaluated 10 min or 24 h later. The same treatments also reduced novel object recognition memory tested 24 h after the sampling phase and when given 15 min before the choice session. These data indicate that D1 receptor stimulation modulates both the encoding and retrieval of object recognition memory. Microinfusion of SKF81297 (0.025 or 0.05 μg/side) into the prelimbic sub-region of the medial prefrontal cortex (mPFC) in this case 10 min before the sampling phase also impaired novel object recognition memory, suggesting that the mPFC is one important site mediating the effects of D1 receptor stimulation on visual recognition memory. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Transcranial Stimulation of the Orbitofrontal Cortex Affects Decisions about Magnocellular Optimized Stimuli

    Directory of Open Access Journals (Sweden)

    Gyula Sáry

    2017-04-01

    Full Text Available Visual categorization plays an important role in fast and efficient information processing; still the neuronal basis of fast categorization has not been established yet. There are two main hypotheses known; both agree that primary, global impressions are based on the information acquired through the magnocellular pathway (MC. It is unclear whether this information is available through the MC that provides information (also for the ventral pathway or through top-down mechanisms by connections between the dorsal pathway and the ventral pathway via the frontal cortex. To clarify this, a categorization task was performed by 48 subjects; they had to make decisions about objects' sizes. We created stimuli specific to the magno- and parvocellular pathway (PC on the basis of their spatial frequency content. Transcranial direct-current stimulation was used to assess the role of frontal areas, a target of the MC. Stimulation did not bias the accuracy of decisions when stimuli optimized for the PC were used. In the case of stimuli optimized for the MC, anodal stimulation improved the subjects' accuracy in the behavioral test, while cathodal stimulation impaired accuracy. Our results support the hypothesis that fast visual categorization processes rely on top-down mechanisms that promote fast predictions through coarse information carried by MC via the orbitofrontal cortex.

  4. Synchronous retinotopic frontal-temporal activity during long-term memory for spatial location.

    Science.gov (United States)

    Slotnick, Scott D

    2010-05-12

    Early visual areas in occipital cortex are known to be retinotopic. Recently, retinotopic maps have been reported in frontal and parietal cortex during spatial attention and working memory. The present event-related potential (ERP) and functional magnetic resonance imaging (fMRI) study determined whether spatial long-term memory was associated with retinotopic activity in frontal and parietal regions, and assessed whether retinotopic activity in these higher level control regions was synchronous with retinotopic activity in lower level visual sensory regions. During encoding, abstract shapes were presented to the left or right of fixation. During retrieval, old and new shapes were presented at fixation and participants classified each shape as old and previously on the "left", old and previously on the "right", or "new". Retinotopic effects were manifested by accurate memory for items previously presented on the left producing activity in the right hemisphere and accurate memory for items previously presented on the right producing activity in the left hemisphere. Retinotopic ERP activity was observed in frontal regions and visual sensory (occipital and temporal) regions. In frontal cortex, retinotopic fMRI activity was localized to the frontal eye fields. There were no significant ERP or fMRI retinotopic memory effects in parietal regions. The present long-term memory retinotopic effects complement previous spatial attention and working memory findings (and suggest retinotopic activity in parietal cortex may require an external peripheral stimulus). Furthermore, ERP cross-correlogram analysis revealed that retinotopic activations in frontal and temporal regions were synchronous, indicating that these regions interact during retrieval of spatial information. (c) 2010 Elsevier B.V. All rights reserved.

  5. Frontal and Parietal Cortical Interactions with Distributed Visual Representations during Selective Attention and Action Selection

    Science.gov (United States)

    Stokes, Mark; Nobre, Anna C.; Rushworth, Matthew F. S.

    2013-01-01

    Using multivoxel pattern analysis (MVPA), we studied how distributed visual representations in human occipitotemporal cortex are modulated by attention and link their modulation to concurrent activity in frontal and parietal cortex. We detected similar occipitotemporal patterns during a simple visuoperceptual task and an attention-to-working-memory task in which one or two stimuli were cued before being presented among other pictures. Pattern strength varied from highest to lowest when the stimulus was the exclusive focus of attention, a conjoint focus, and when it was potentially distracting. Although qualitatively similar effects were seen inside regions relatively specialized for the stimulus category and outside, the former were quantitatively stronger. By regressing occipitotemporal pattern strength against activity elsewhere in the brain, we identified frontal and parietal areas exerting top-down control over, or reading information out from, distributed patterns in occipitotemporal cortex. Their interactions with patterns inside regions relatively specialized for that stimulus category were higher than those with patterns outside those regions and varied in strength as a function of the attentional condition. One area, the frontal operculum, was distinguished by selectively interacting with occipitotemporal patterns only when they were the focus of attention. There was no evidence that any frontal or parietal area actively inhibited occipitotemporal representations even when they should be ignored and were suppressed. Using MVPA to decode information within these frontal and parietal areas showed that they contained information about attentional context and/or readout information from occipitotemporal cortex to guide behavior but that frontal regions lacked information about category identity. PMID:24133250

  6. Meningocortical lesion increases expression of the cholecystokinin gene in rat cerebral cortex: evidence for the involvement of platelet-activating factor (PAF).

    Science.gov (United States)

    Götz, E; Olenik, C; Uhl, A; Seregi, A; Meyer, D K

    1993-06-01

    In rat neocortex, interneurons express the gene encoding cholecystokinin. After an injury to the meninges and the underlying cortex the levels of cholecystokinin mRNA are transiently enhanced in the ipsilateral hemisphere. In the present study, we have investigated, whether platelet-activating factor plays a role in this phenomenon. Two antagonists of platelet-activating receptors, i.e. WEB 2086 (1.5 mg/kg) and brotizolam (10 mg/kg), were used. When injected 30 min prior to the injury of the parietal cortex, both agents reduced the rise in the concentration of cholecystokinin mRNA in frontal cortex by approximately 60%. They had no significant effect when given 30 min after the injury. Our finding that antagonists of platelet-activating factor receptors diminish the injury-induced change in the activity of cholecystokinin-interneurons opens the possibility that these agents may also affect other pathophysiological aspects of brain trauma.

  7. Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

    Science.gov (United States)

    Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

    2017-01-01

    The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

  8. Frontal Brain Asymmetry and Willingness to Pay.

    Science.gov (United States)

    Ramsøy, Thomas Z; Skov, Martin; Christensen, Maiken K; Stahlhut, Carsten

    2018-01-01

    Consumers frequently make decisions about how much they are willing to pay (WTP) for specific products and services, but little is known about the neural mechanisms underlying such calculations. In this study, we were interested in testing whether specific brain activation-the asymmetry in engagement of the prefrontal cortex-would be related to consumer choice. Subjects saw products and subsequently decided how much they were willing to pay for each product, while undergoing neuroimaging using electroencephalography. Our results demonstrate that prefrontal asymmetry in the gamma frequency band, and a trend in the beta frequency band that was recorded during product viewing was significantly related to subsequent WTP responses. Frontal asymmetry in the alpha band was not related to WTP decisions. Besides suggesting separate neuropsychological mechanisms of consumer choice, we find that one specific measure-the prefrontal gamma asymmetry-was most strongly related to WTP responses, and was most coupled to the actual decision phase. These findings are discussed in light of the psychology of WTP calculations, and in relation to the recent emergence of consumer neuroscience and neuromarketing.

  9. Assessing the Effect of Early Visual Cortex Transcranial Magnetic Stimulation on Working Memory Consolidation.

    Science.gov (United States)

    van Lamsweerde, Amanda E; Johnson, Jeffrey S

    2017-07-01

    Maintaining visual working memory (VWM) representations recruits a network of brain regions, including the frontal, posterior parietal, and occipital cortices; however, it is unclear to what extent the occipital cortex is engaged in VWM after sensory encoding is completed. Noninvasive brain stimulation data show that stimulation of this region can affect working memory (WM) during the early consolidation time period, but it remains unclear whether it does so by influencing the number of items that are stored or their precision. In this study, we investigated whether single-pulse transcranial magnetic stimulation (spTMS) to the occipital cortex during VWM consolidation affects the quantity or quality of VWM representations. In three experiments, we disrupted VWM consolidation with either a visual mask or spTMS to retinotopic early visual cortex. We found robust masking effects on the quantity of VWM representations up to 200 msec poststimulus offset and smaller, more variable effects on WM quality. Similarly, spTMS decreased the quantity of VWM representations, but only when it was applied immediately following stimulus offset. Like visual masks, spTMS also produced small and variable effects on WM precision. The disruptive effects of both masks and TMS were greatly reduced or entirely absent within 200 msec of stimulus offset. However, there was a reduction in swap rate across all time intervals, which may indicate a sustained role of the early visual cortex in maintaining spatial information.

  10. Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning.

    Science.gov (United States)

    Sliwinska, Magdalena W; Violante, Inês R; Wise, Richard J S; Leech, Robert; Devlin, Joseph T; Geranmayeh, Fatemeh; Hampshire, Adam

    2017-08-09

    It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword-object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary. SIGNIFICANCE STATEMENT Learning a task involves the brain system within which that specific task becomes established. Therefore, successfully learning a new vocabulary establishes the novel words in the language system. However, there is evidence that in the early stages of learning, networks within multiple-demand cortex (MDC), which control higher cognitive functions, such as working memory, attention, and monitoring of performance, become active. This activity

  11. Frontal assessment battery and frontal atrophy in amyotrophic lateral sclerosis

    OpenAIRE

    Terada, Tatsuhiro; Miyata, Jun; Obi, Tomokazu; Kubota, Manabu; Yoshizumi, Miho; Yamazaki, Kinya; Mizoguchi, Kouichi; Murai, Toshiya

    2017-01-01

    Abstract Objectives To determine the potential utility of the frontal assessment battery (FAB) in assessing cognitive impairments in amyotrophic lateral sclerosis (ALS), we investigated the association between the FAB score and regional gray matter volume, and ascertained whether the regional brain alterations related to cognitive impairments occur in relatively mild stage of ALS. Materials and Methods Twenty?four ALS patients with a Mini?Mental State Examination score of >23, a normal score ...

  12. Role of beta1-adrenoreceptors at visual associative cortex in rats of different age in the impact on autonomous regulation of the heart rate ander low atmospheric pressure

    Directory of Open Access Journals (Sweden)

    Наталія Михайлівна Волкова

    2015-11-01

    Full Text Available The role of beta1-adrenoreceptors at visual associative cortex in rats of different age in the impact on autonomous regulation of the heart rate ander low atmospheric pressure was investigated. The aim of the study was to check expediency of application nebivolol to prevent the adverse effects of hypoxic environment, the pressure conditions similar to the third type of weather.Methods. In the experimental group cardiointervalography recorded in the intact condition before hypoxia, after hypoxic exposure, after trepanation of the skull and applying the solution beta1-blocker nebivolol (0.5 mg / kg through the trepanation hole on the surface of the cerebral cortex (there were separate groups with right-sided and left-sided trepanation in projection of cortical areas Oc2L, with subsequent automatic analysis of data on a personal computer. In the control group a similar procedure of the experiment was carried out excepting hypoxic exposure. Effect of hypoxic atmosphere was created by reducing pressure by 50.76 hPa (0.05 atm in the Komovsky’s device and hold the anesthetized rat under a glass bell for 1 hour.Results. In juvenile, adult and old intact rats beta1-receptor structures in left and right associative cortical fields Oc2L are included to the neural circuits that provide growth of functional strenuousness in regulation of heart rhythm. After hypoxic exposure beta1-adrenoreceptors in the left field Oc2L are included in other neural circuits, and take part in limiting the functional strenuousness in regulation of heart rhythm.Conclusions. Experimental results about effectiveness of therapeutic doses of beta-1 adrenoblockers especially nebivolol in adult and old age for prevention of unfavorable effects of hypoxic medium that corresponds to the baric conditions of 111type weather are to be verified by the clinical observations

  13. Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception

    Science.gov (United States)

    Ferrier, Jérémy; Bayet-Robert, Mathilde; Dalmann, Romain; El Guerrab, Abderrahim; Aissouni, Youssef; Graveron-Demilly, Danielle; Chalus, Maryse; Pinguet, Jérémy; Eschalier, Alain; Richard, Damien; Daulhac, Laurence; Balayssac, David

    2015-01-01

    Neuropathic pain is one of the most debilitating pain conditions, yet no therapeutic strategy has been really effective for its treatment. Hence, a better understanding of its pathophysiological mechanisms is necessary to identify new pharmacological targets. Here, we report important metabolic variations in brain areas involved in pain processing in a rat model of oxaliplatin-induced neuropathy using HRMAS 1H-NMR spectroscopy. An increased concentration of choline has been evidenced in the posterior insular cortex (pIC) of neuropathic animal, which was significantly correlated with animals' pain thresholds. The screening of 34 genes mRNA involved in the pIC cholinergic system showed an increased expression of the high-affinity choline transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analysis in oxaliplatin-treated rats and the spared nerve injury model (SNI). Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely reversed oxaliplatin-induced mechanical allodynia. Consistently, systemic treatment with donepezil, a centrally active acetylcholinesterase inhibitor, prevented and reversed oxaliplatin-induced cold and mechanical allodynia as well as social interaction impairment. Intracerebral microdialysis revealed a lower level of acetylcholine in the pIC of oxaliplatin-treated rats, which was significantly increased by donepezil. Finally, the analgesic effect of donepezil was markedly reduced by a microinjection of the M2 antagonist, methoctramine, within the pIC, in both oxaliplatin-treated rats and spared nerve injury rats. These findings highlight the crucial role of cortical cholinergic neurotransmission as a critical mechanism of neuropathic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used for neuropathic pain treatment. SIGNIFICANCE STATEMENT Our study describes a decrease in cholinergic neurotransmission in the posterior insular

  14. Dissociation of the role of the prelimbic cortex in interval timing and resource allocation: beneficial effect of norepinephrine and dopamine reuptake inhibitor nomifensine on anxiety-inducing distraction

    Directory of Open Access Journals (Sweden)

    Alexander R Matthews

    2012-12-01

    Full Text Available Emotional distracters impair cognitive function. Emotional processing is dysregulated in affective disorders such as depression, phobias, schizophrenia, and PTSD. Among the processes impaired by emotional distracters, and whose dysregulation is documented in affective disorders, is the ability to time in the seconds-to-minutes range, i.e. interval timing. Presentation of task-irrelevant distracters during a timing task results in a delay in responding suggesting a failure to maintain subjective time in working memory, possibly due to attentional and working memory resources being diverted away from timing, as proposed by the Relative Time-Sharing model. We investigated the role of the prelimbic cortex in the detrimental effect of anxiety-inducing task-irrelevant distracters on the cognitive ability to keep track of time, using local infusions of norepinephrine and dopamine reuptake inhibitor nomifensine in a modified peak-interval procedure with neutral and anxiety-inducing distracters. Given that some antidepressants have beneficial effects on attention and working memory, e.g., decreasing emotional response to negative events, we hypothesized that nomifensine would improve maintenance of information in working memory in trials with distracters, resulting in a decrease of the disruptive effect of emotional events on the timekeeping abilities. Our results revealed a dissociation of the effects of nomifensine infusion in prelimbic cortex between interval timing and resource allocation, and between neutral and anxiety-inducing distraction. Nomifensine was effective only during trials with distracters, but not during trials without distracters. Nomifensine reduced the detrimental effect of the distracters only when the distracters were anxiety-inducing, but not when they were neutral. Results are discussed in relation to the brain circuits involved in Relative Time-Sharing of resources, and the pharmacological management of affective disorders.

  15. Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample.

    Science.gov (United States)

    Carlson, Joshua M; Depetro, Emily; Maxwell, Joshua; Harmon-Jones, Eddie; Hajcak, Greg

    2015-08-30

    Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Contribution of different regions of the prefrontal cortex and lesion laterality to deficit of decision-making on the Iowa Gambling Task.

    Science.gov (United States)

    Ouerchefani, Riadh; Ouerchefani, Naoufel; Allain, Philippe; Ben Rejeb, Mohamed Riadh; Le Gall, Didier

    2017-02-01

    Few studies have examined the contribution of different sub-regions of the prefrontal cortex and lesion laterality to decision-making abilities. In addition, there are inconsistent findings about the role of ventromedial and dorsolateral lesions in decision-making deficit. In this study, decision-making processes are investigated following different damaged areas of the prefrontal cortex. We paid particular attention to the contribution of laterality, lesion location and lesion volume in decision-making deficit. Twenty-seven patients with discrete ventromedial lesions, dorsolateral lesions or extended-frontal lesions were compared with normal subjects on the Iowa Gambling Task (IGT). Our results showed that all frontal subgroups were impaired on the IGT in comparison with normal subjects. We noted also that IGT performance did not vary systematically based on lesion laterality or location. More precisely, our lesion analysis revealed that decision-making processes depend on a large cerebral network, including both ventromedial and dorsolateral areas of the prefrontal cortex. Consistent with past findings, our results support the claim that IGT deficit is not solitarily associated with ventromedial prefrontal cortex lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Cognitive performance change of pediatric patients after conducting frontal transcortical approach to treat lateral ventricular tumor.

    Science.gov (United States)

    Zhu, Wanchun; He, Jintao; Li, Xiang; Wang, Lei; Lu, Zheng; Li, Chunde; Gong, Jian

    2017-12-01

    Applying frontal transcortical approach to treat lateral ventricular tumor is one of the most common neurosurgical manipulations. The frontal transcortical approach generally passes through the middle frontal gyrus in which there is no major function involved in the traditional sense. However, current researches have suggested that the prefrontal cortex (PFC) plays a central role in the whole network of the brain cognitive frame. In addition, cognitive function is crucial in growing and developmental stages and essential for the educational achievement, especially for children. Based on this, the authors in this study analyzed cognitive performance change of pediatric patients who had accepted frontal transcortical operation in 1-year follow-up and discussed the possibility of higher cognitive functions of the damaged region. In this single-center study, 15 pediatric patients (median age at surgery, 9.21 years old; range, 6.42-14.17 years old) who had been treated with frontal transcortical approach for lateral ventricular tumors were selected as research objects. The cognitive function assessment was conducting by adopting the revised Wechsler Intelligence Scale for Children-fourth edition (WISC-IV). In addition, the resting-state functional magnetic resonance imaging (resting-state fMRI) and diffusion tensor imaging (DTI) were carried out to measure the level of co-activation and to explore the functional connectivity between the brain regions at the preoperative period and 1-year follow-up after surgery. GTR was achieved in all patients, and all patients were in good condition after surgery. Compared to the preoperative indices of WISC-IV, patients generally had a lower level of indices of the WISC-IV after surgery, for example, the total IQ was declined to M = 83.60, SD = 9.500 from M = 95.33, SD = 13.844 within 1 year convalescence. The data of perceptual reasoning (t = - 2.392, p = 0.016), processing speed (t = - 2.121, p = 0.033), and

  18. Amygdala-prefrontal cortex resting-state functional connectivity varies with first depressive or manic episode in bipolar disorder.

    Science.gov (United States)

    Wei, Shengnan; Geng, Haiyang; Jiang, Xiaowei; Zhou, Qian; Chang, Miao; Zhou, Yifang; Xu, Ke; Tang, Yanqing; Wang, Fei

    2017-02-22

    Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (pamygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (pamygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

    DEFF Research Database (Denmark)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo

    2017-01-01

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field...... of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5 mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time...... spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin...

  20. 3-D Cytoarchitectonic parcellation of human orbitofrontal cortex Correlation with postmortem MRI

    NARCIS (Netherlands)

    Uylings, H.B.M.; Sanz-Arigita, E.J.; Vos, K.; Pool, C.W.; Evers, P.; Rajkowska, G.

    2010-01-01

    The orbitofrontal cortex (OFC) is located on the basal surface of the frontal lobe and is distinguished by its unique anatomical and functional features. Clinical and postmortem studies suggest the involvement of the orbitofrontal cortex in psychiatric disorders. However, the exact parcellation of

  1. The IMM Frontal Face Database

    DEFF Research Database (Denmark)

    Fagertun, Jens; Stegmann, Mikkel Bille

    2005-01-01

    This note describes a data set consisting of 120 annotated monocular images of 12 different frontal human faces. Points of correspondence are placed on each image so the data set can be readily used for building statistical models of shape. Format specifications and terms of use are also given in...... in this note. The data set is available in two versions: i) low resolution, given in the zip-file electronic version, ii) high, given in the publication link....

  2. Task constraints modulate activation in right ventral lateral prefrontal cortex.

    Science.gov (United States)

    Vartanian, Oshin; Goel, Vinod

    2005-10-01

    Lesion data suggest that right prefrontal cortex (PFC) plays a critical role in open-ended problem solving. To test this hypothesis, we scanned fifteen normal subjects with fMRI as they completed three types of anagram problems varying in the level of constraints placed on the search space. On unconstrained trials, they rearranged letters to generate solutions (e.g., Can you make a "Word with ZJAZ?"). On semantically constrained trials, they rearranged letters to generate solutions within particular semantic categories (e.g., Can you make a type of "Music with ZJAZ?"). On baseline trials, they rearranged letters to make specific words (e.g., Can you make the word "JAZZ with ZJAZ?"). As predicted, the critical comparison of unconstrained vs. semantically constrained trials revealed significant activation in right ventral lateral PFC, as well as left superior frontal gyrus, frontopolar cortex, right superior parietal lobe, right post central gyrus, and the occipital-parietal sulcus. Furthermore, activation in right ventral lateral PFC (BA 47) increased as the constraints placed on the anagram search space were reduced. We argue that the activation in right ventral lateral PFC is related to hypothesis generation in unconstrained settings, whereas activation in other structures is related to additional processes linked to anagram problems such as semantic retrieval, semantic categorization, and cognitive monitoring. These results extend the lesion data and imaging studies by demonstrating that a relative absence of constraints on the solution space is sufficient to engage right ventral lateral PFC in hypothesis generation tasks.

  3. Pure apraxia of speech due to infarct in premotor cortex.

    Science.gov (United States)

    Patira, Riddhi; Ciniglia, Lauren; Calvert, Timothy; Altschuler, Eric L

    Apraxia of speech (AOS) is now recognized as an articulation disorder distinct from dysarthria and aphasia. Various lesions have been associated with AOS in studies that are limited in precise localization due to variability in size and type of pathology. We present a case of pure AOS in setting of an acute stroke to localize more precisely than ever before the brain area responsible for AOS, dorsal premotor cortex (dPMC). The dPMC is in unique position to plan and coordinate speech production by virtue of its connection with nearby motor cortex harboring corticobulbar tract, supplementary motor area, inferior frontal operculum, and temporo-parietal area via the dorsal stream of dual-stream model of speech processing. The role of dPMC is further supported as part of dorsal stream in the dual-stream model of speech processing as well as controller in the hierarchical state feedback control model. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. Frontal brain asymmetry as a marker of depression and effectiveness of TMS therapy

    International Nuclear Information System (INIS)

    Mani, D.; Lithgow, B.

    2010-01-01

    Full text: Resting frontal brain electroencephalography (EEG) asymmetry has been hypothesi sed as a diagnostic marker for depression. A number of studies have shown that depressed individuals are characterised by diminished left sided activation of the prefrontal cortex, which is indicated by greater left than right alpha-band power. Relative left frontal region activity is believed to be associated with positive approach related behaviour and relative right frontal activity is seen to be linked to negative withdrawal related behaviour. In this study, frontal brain EEG was recorded from 17 depressed and 19 control subjects, from which frontal brain asymmetry ratios were calculated. The results confirmed the trend of relative left anterior hypoaclivation for individuals with depression compared to the healthy controls. This study also looked at beta and theta band ratios and found theta for depressed is predominantly negative, while the control group dis played mainly positive values. Beta comparison showed little significant difference between control and depressed groups. In addition, there have been few studies that examined frontal brain asymmetry in depression soon after treatment to gauge its effectiv ness. In a very preliminary study, the effect of Transcranial Magnetic Stimulation (TMS) therapy on the alpha band frontal brain asymmetry ratio for 5 depl'essed subjects before and after treatment found a slight increase in FBA ratio for 4 subjects. Further research and a larger subject group is required to validate these results.

  5. The relation of hedonic hunger and restrained eating to lateralized frontal activation.

    Science.gov (United States)

    Winter, S R; Feig, E H; Kounios, J; Erickson, B; Berkowitz, S; Lowe, M R

    2016-09-01

    Asymmetrical alpha activation in the prefrontal cortex (frontal asymmetry) in electroencephalography (EEG) has been related to eating behavior. Prior studies linked dietary restraint with right frontal asymmetry [1] and disinhibition with left frontal asymmetry [2]. The current study simultaneously assessed restrained eating and hedonic hunger (drive for food reward in the absence of hunger) in relation to frontal asymmetry. Resting-state EEG and measures of restrained eating (Revised Restraint Scale; RRS) and hedonic hunger (Power of Food Scale; PFS) were assessed in 61 non-obese adults. Individually, hedonic hunger predicted left asymmetry. However, PFS and RRS were correlated (r=0.48, phunger exhibited left asymmetry irrespective of RRS scores; among those low in PFS, only those high in RRS showed right asymmetry. Results were consistent with literature linking avoidant behaviors (restraint) with right-frontal asymmetry and approach behaviors (binge eating) with left-frontal asymmetry. It appears that a strong drive toward palatable foods predominates at a neural level even when restraint is high. Findings suggest that lateralized frontal activity is an indicator of motivation both to consume and to avoid consuming highly palatable foods. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Historical Evolution of the Frontal Lobe Syndrome

    NARCIS (Netherlands)

    Krudop, W.A.; Pijnenburg, Y.A.L.

    2015-01-01

    The function of the frontal lobes and the related frontal lobe syndrome have not been described in detail until relatively late in history. Slowly, the combination of knowledge from animal models, the detailed examination of symptoms after traumatic frontal lobe injuries, and the rise and fall of

  7. Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction.

    Science.gov (United States)

    Arnsten, Amy F T

    2009-01-01

    Recent advances in neurobiology have aided our understanding of attention-deficit hyperactivity disorder (ADHD). The higher-order association cortices in the temporal and parietal lobes and prefrontal cortex (PFC) interconnect to mediate aspects of attention. The parietal association cortices are important for orienting attentional resources in time/space, while the temporal association cortices analyse visual features critical for identifying objects/places. These posterior cortices are engaged by the salience of a stimulus (its physical characteristics such as movement and colour). Conversely, the PFC is critical for regulating attention based on relevance (i.e. its meaning). The PFC is important for screening distractions, sustaining attention and shifting/dividing attention in a task-appropriate manner. The PFC is critical for regulating behaviour/emotion, especially for inhibiting inappropriate emotions, impulses and habits. The PFC is needed for allocating/planning to achieve goals and organizing behaviour/thought. These regulatory abilities are often referred to as executive functions. In humans, the right hemisphere of the PFC is important for regulating distractions, inappropriate behaviour and emotional responses. Imaging studies of patients with ADHD indicate that these regions are underactive with weakened connections to other parts of the brain. The PFC regulates attention and behaviour through networks of interconnected pyramidal cells. These networks excite each other to store goals/rules to guide actions and are highly dependent on their neurochemical environment, as small changes in the catecholamines noradrenaline (NA) or dopamine (DA) can have marked effects on PFC function. NA and DA are released in the PFC according to our arousal state; too little (during fatigue or boredom) or too much (during stress) impairs PFC function. Optimal amounts are released when we are alert/interested. The beneficial effects of NA occur at postsynaptic alpha(2A

  8. The role of the lateral occipital cortex in aesthetic appreciation of representational and abstract paintings: a TMS study.

    Science.gov (United States)

    Cattaneo, Zaira; Lega, Carlotta; Ferrari, Chiara; Vecchi, Tomaso; Cela-Conde, Camilo José; Silvanto, Juha; Nadal, Marcos

    2015-04-01

    Neuroimaging studies of aesthetic appreciation have shown that activity in the lateral occipital area (LO)-a key node in the object recognition pathway-is modulated by the extent to which visual artworks are liked or found beautiful. However, the available evidence is only correlational. Here we used transcranial magnetic stimulation (TMS) to investigate the putative causal role of LO in the aesthetic appreciation of paintings. In our first experiment, we found that interfering with LO activity during aesthetic appreciation selectively reduced evaluation of representational paintings, leaving appreciation of abstract paintings unaffected. A second experiment demonstrated that, although the perceived clearness of the images overall positively correlated with liking, the detrimental effect of LO TMS on aesthetic appreciation does not owe to TMS reducing perceived clearness. Taken together, our findings suggest that object-recognition mechanisms mediated by LO play a causal role in aesthetic appreciation of representational art. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Pavlović D.M.

    2009-01-01

    Full Text Available The anterior cingulate cortex (ACC has a role in attention, analysis of sensory information, error recognition, problem solving, detection of novelty, behavior, emotions, social relations, cognitive control, and regulation of visceral functions. This area is active whenever the individual feels some emotions, solves a problem, or analyzes the pros and cons of an action (if it is a right decision. Analogous areas are also found in higher mammals, especially whales, and they contain spindle neurons that enable complex social interactions. Disturbance of ACC activity is found in dementias, schizophrenia, depression, the obsessive-compulsive syndrome, and other neuropsychiatric diseases.

  10. Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings.

    Directory of Open Access Journals (Sweden)

    Yixuan Ku

    2007-08-01

    Full Text Available Our previous studies on scalp-recorded event-related potentials (ERPs showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA to the ERP data, we found independent components (ICs located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC and the primary somatosensory cortex (SI. The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex that are involved in sensation and perception of various stimuli.

  11. Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings.

    Science.gov (United States)

    Ku, Yixuan; Ohara, Shinji; Wang, Liping; Lenz, Fred A; Hsiao, Steven S; Bodner, Mark; Hong, Bo; Zhou, Yong-Di

    2007-08-22

    Our previous studies on scalp-recorded event-related potentials (ERPs) showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA) to the ERP data, we found independent components (ICs) located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC) and the primary somatosensory cortex (SI). The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex) that are involved in sensation and perception of various stimuli.

  12. Manipulation of the extrastriate frontal loop can resolve visual disability in blindsight patients.

    Science.gov (United States)

    Badgaiyan, Rajendra D

    2012-12-01

    Patients with blindsight are not consciously aware of visual stimuli in the affected field of vision but retain nonconscious perception. This disability can be resolved if nonconsciously perceived information can be brought to their conscious awareness. It can be accomplished by manipulating neural network of visual awareness. To understand this network, we studied the pattern of cortical activity elicited during processing of visual stimuli with or without conscious awareness. The analysis indicated that a re-entrant signaling loop between the area V3A (located in the extrastriate cortex) and the frontal cortex is critical for processing conscious awareness. The loop is activated by visual signals relayed in the primary visual cortex, which is damaged in blindsight patients. Because of the damage, V3A-frontal loop is not activated and the signals are not processed for conscious awareness. These patients however continue to receive visual signals through the lateral geniculate nucleus. Since these signals do not activate the V3A-frontal loop, the stimuli are not consciously perceived. If visual input from the lateral geniculate nucleus is appropriately manipulated and made to activate the V3A-frontal loop, blindsight patients can regain conscious vision. Published by Elsevier Ltd.

  13. Mindfulness based cognitive therapy improves frontal control in bipolar disorder: a pilot EEG study

    Directory of Open Access Journals (Sweden)

    Howells Fleur M

    2012-02-01

    Full Text Available Abstract Background Cognitive processing in Bipolar Disorder is characterized by a number of attentional abnormalities. Mindfulness Based Cognitive Therapy combines mindfulness meditation, a form of attentional training, along with aspects of cognitive therapy, and may improve attentional dysfunction in bipolar disorder patients. Methods 12 euthymic BD patients and 9 control participants underwent record of electroencephalography (EEG, band frequency analysis during resting states (eyes open, eyes closed and during the completion of a continuous performance task (A-X version, EEG event-related potential (ERP wave component analysis. The individuals with BD completed an 8-week MBCT intervention and record of EEG was repeated. Results (1 Brain activity, individuals with BD showed significantly decreased theta band power, increased beta band power, and decreased theta/beta ratios during the resting state, eyes closed, for frontal and cingulate cortices. Post MBCT intervention improvement over the right frontal cortex was seen in the individuals with BD, as beta band power decreased. (2 Brain activation, individuals with BD showed a significant P300-like wave form over the frontal cortex during the cue. Post MBCT intervention the P300-like waveform was significantly attenuated over the frontal cortex. Conclusions Individuals with BD show decreased attentional readiness and activation of non-relevant information processing during attentional processes. These data are the first that show, MBCT in BD improved attentional readiness, and attenuated activation of non-relevant information processing during attentional processes.

  14. Human Frontal-Subcortical Circuit and Asymmetric Belief Updating.

    Science.gov (United States)

    Moutsiana, Christina; Charpentier, Caroline J; Garrett, Neil; Cohen, Michael X; Sharot, Tali

    2015-10-21

    How humans integrate information to form beliefs about reality is a question that has engaged scientists for centuries, yet the biological system supporting this process is not well understood. One of the most salient attributes of information is valence. Whether a piece of news is good or bad is critical in determining whether it will alter our beliefs. Here, we reveal a frontal-subcortical circuit in the left hemisphere that is simultaneously associated with enhanced integration of favorable information into beliefs and impaired integration of unfavorable information. Specifically, for favorable information, stronger white matter connectivity within this system, particularly between the left inferior frontal gyrus (IFG) and left subcortical regions (including the amygdala, hippocampus, thalamus, putamen, and pallidum), as well as insular cortex, is associated with greater change in belief. However, for unfavorable information, stronger connectivity within this system, particularly between the left IFG and left pallidum, putamen, and insular cortex, is associated with reduced change in beliefs. These novel results are consistent with models suggesting that partially separable processes govern learning from favorable and unfavorable information. Beliefs of what may happen in the future are important, because they guide decisions and actions. Here, we illuminate how structural brain connectivity is related to the generation of subjective beliefs. We focus on how the valence of information is related to people's tendency to alter their beliefs. By quantifying the extent to which participants update their beliefs in response to desirable and undesirable information and relating those measures to the strength of white matter connectivity using diffusion tensor imaging, we characterize a left frontal-subcortical system that is associated simultaneously with greater belief updating in response to favorable information and reduced belief updating in response to

  15. Neurovascular coupling and decoupling in the cortex during voluntary locomotion.

    Science.gov (United States)

    Huo, Bing-Xing; Smith, Jared B; Drew, Patrick J

    2014-08-13

    Hemodynamic signals are widely used to infer neural activity in the brain. We tested the hypothesis that hemodynamic signals faithfully report neural activity during voluntary behaviors by measuring cerebral blood volume (CBV) and neural activity in the somatosensory cortex and frontal cortex of head-fixed mice during locomotion. Locomotion induced a large and robust increase in firing rate and gamma-band (40-100 Hz) power in the local field potential in the limb representations in somatosensory cortex, and was accompanied by increases in CBV, demonstrating that hemodynamic signals are coupled with neural activity in this region. However, in the frontal cortex, CBV did not change during locomotion, but firing rate and gamma-band power both increased, indicating a decoupling of neural activity from the hemodynamic signal. These results show that hemodynamic signals are not faithful indicators of the mean neural activity in the frontal cortex during locomotion; thus, the results from fMRI and other hemodynamic imaging methodologies for studying neural processes must be interpreted with caution. Copyright © 2014 the authors 0270-6474/14/3410975-07$15.00/0.

  16. Functional magnetic resonance imaging of the frontal eye fields during saccadic eye movements

    International Nuclear Information System (INIS)

    Miki, Atsushi; Takagi, Mineo; Abe, Haruki; Nakajima, Takashi; Miyauchi, Satoru.

    1996-01-01

    We evaluated activity-induced signal intensity changes in the human cerebral cortex during horizontal saccadic eye movements using functional magnetic resonance imaging (fMRI) based on the blood-oxygenation-level-dependent (BOLD) contrast method. Compared with central fixation, significant signal increases were observed bilaterally in the middle frontal gyrus (Brodmann area 8) during saccadic conditions. The location of the activated area was consistent with that of previously reported frontal eye fields (FEF). These results suggest that fMRI has potential merit for the study of cortical control of eye movements in humans. (author)

  17. The Significance of Memory in Sensory Cortex.

    Science.gov (United States)

    Muckli, Lars; Petro, Lucy S

    2017-05-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. The significance of memory in sensory cortex

    OpenAIRE

    Muckli, Lars; Petro, Lucy S.

    2017-01-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

  19. Frontal lobe seizures: from clinical semiology to localization.

    Science.gov (United States)

    Bonini, Francesca; McGonigal, Aileen; Trébuchon, Agnès; Gavaret, Martine; Bartolomei, Fabrice; Giusiano, Bernard; Chauvel, Patrick

    2014-02-01

    Frontal lobe seizures are difficult to characterize according to semiologic and electrical features. We wished to establish whether different semiologic subgroups can be identified and whether these relate to anatomic organization. We assessed all seizures from 54 patients with frontal lobe epilepsy that were explored with stereoelectroencephalography (SEEG) during presurgical evaluation. Semiologic features and concomitant intracerebral EEG changes were documented and quantified. These variables were examined using Principal Component Analysis and Cluster Analysis, and semiologic features correlated with anatomic localization. Four main groups of patients were identified according to semiologic features, and correlated with specific patterns of anatomic seizure localization. Group 1 was characterized clinically by elementary motor signs and involved precentral and premotor regions. Group 2 was characterized by a combination of elementary motor signs and nonintegrated gestural motor behavior, and involved both premotor and prefrontal regions. Group 3 was characterized by integrated gestural motor behavior with distal stereotypies and involved anterior lateral and medial prefrontal regions. Group 4 was characterized by seizures with fearful behavior and involved the paralimbic system (ventromedial prefrontal cortex ± anterior temporal structures). The groups were organized along a rostrocaudal axis, representing bands within a spectrum rather than rigid categories. The more anterior the seizure organization, the more likely was the occurrence of integrated behavior during seizures. Distal stereotypies were associated with the most anterior prefrontal localizations, whereas proximal stereotypies occurred in more posterior prefrontal regions. Meaningful categorization of frontal seizures in terms of semiology is possible and correlates with anatomic organization along a rostrocaudal axis, in keeping with current hypotheses of frontal lobe hierarchical organization

  20. Auditory and visual connectivity gradients in frontoparietal cortex.

    Science.gov (United States)

    Braga, Rodrigo M; Hellyer, Peter J; Wise, Richard J S; Leech, Robert

    2017-01-01

    A frontoparietal network of brain regions is often implicated in both auditory and visual information processing. Although it is possible that the same set of multimodal regions subserves both modalities, there is increasing evidence that there is a differentiation of sensory function within frontoparietal cortex. Magnetic resonance imaging (MRI) in humans was used to investigate whether different frontoparietal regions showed intrinsic biases in connectivity with visual or auditory modalities. Structural connectivity was assessed with diffusion tractography and functional connectivity was tested using functional MRI. A dorsal-ventral gradient of function was observed, where connectivity with visual cortex dominates dorsal frontal and parietal connections, while connectivity with auditory cortex dominates ventral frontal and parietal regions. A gradient was also observed along the posterior-anterior axis, although in opposite directions in prefrontal and parietal cortices. The results suggest that the location of neural activity within frontoparietal cortex may be influenced by these intrinsic biases toward visual and auditory processing. Thus, the location of activity in frontoparietal cortex may be influenced as much by stimulus modality as the cognitive demands of a task. It was concluded that stimulus modality was spatially encoded throughout frontal and parietal cortices, and was speculated that such an arrangement allows for top-down modulation of modality-specific information to occur within higher-order cortex. This could provide a potentially faster and more efficient pathway by which top-down selection between sensory modalities could occur, by constraining modulations to within frontal and parietal regions, rather than long-range connections to sensory cortices. Hum Brain Mapp 38:255-270, 2017. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  1. Prefrontal cortex connectivity dysfunction in performing the Fist–Edge–Palm task in patients with first-episode schizophrenia and non-psychotic first-degree relatives

    Directory of Open Access Journals (Sweden)

    Raymond C.K. Chan

    2015-01-01

    Full Text Available Neurological soft signs have been considered one of the promising neurological endophenotypes for schizophrenia. However, most previous studies have employed clinical rating data only. The present study aimed to examine the neurobiological basis of one of the typical motor coordination signs, the Fist–Edge–Palm (FEP task, in patients with first-episode schizophrenia and their non-psychotic first degree relatives. Thirteen patients with first-episode schizophrenia, 14 non-psychotic first-degree relatives and 14 healthy controls were recruited. All of them were instructed to perform the FEP task in a 3 T GE Machine. Psychophysiological interaction (PPI analysis was used to evaluate the functional connectivity between the sensorimotor cortex and frontal regions when participants performed the FEP task compared to simple motor tasks. In the contrast of palm-tapping (PT vs. rest, activation of the left frontal–parietal region was lowest in the schizophrenia group, intermediate in the relative group and highest in the healthy control group. In the contrast of FEP vs. PT, patients with schizophrenia did not show areas of significant activation, while relatives and healthy controls showed significant activation of the left middle frontal gyrus. Moreover, with the increase in task complexity, significant functional connectivity was observed between the sensorimotor cortex and the right frontal gyrus in healthy controls but not in patients with first episode schizophrenia. These findings suggest that activity of the left frontal–parietal and frontal regions may be neurofunctional correlates of neurological soft signs, which in turn may be a potential endophenotype of schizophrenia. Moreover, the right frontal gyrus may play a specific role in the execution of the FEP task in schizophrenia spectrum disorders.

  2. Motor cortex neuroplasticity following brachial plexus transfer

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    Stefan eDimou

    2013-08-01

    Full Text Available In the past decade, research has demonstrated that cortical plasticity, once thought only to exist in the early stages of life, does indeed continue on into adulthood. Brain plasticity is now acknowledged as a core principle of brain function and describes the ability of the central nervous system to adapt and modify its structural organization and function as an adaptive response to functional demand. In this clinical case study we describe how we used neuroimaging techniques to observe the functional topographical expansion of a patch of cortex along the sensorimotor cortex of a 27 year-old woman following brachial plexus transfer surgery to re-innervate her left arm. We found bilateral activations present in the thalamus, caudate, insula as well as across the sensorimotor cortex during an elbow flex motor task. In contrast we found less activity in the sensorimotor cortex for a finger tap motor task in addition to activations lateralised to the left inferior frontal gyrus and thalamus and bilaterally for the insula. From a pain perspective the patient who had experienced extensive phantom limb pain before surgery found these sensations were markedly reduced following transfer of the right brachial plexus to the intact left arm. Within the context of this clinical case the results suggest that functional improvements in limb mobility are associated with increased activation in the sensorimotor cortex as well as reduced phantom limb pain.

  3. Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor.

    Science.gov (United States)

    Freitas, Renato Leonardo de; Salgado-Rohner, Carlos José; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre de Souza; Coimbra, Norberto Cysne

    2013-09-01

    It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline.

  4. Reasoning by analogy requires the left frontal pole: lesion-deficit mapping and clinical implications.

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    Urbanski, Marika; Bréchemier, Marie-Laure; Garcin, Béatrice; Bendetowicz, David; Thiebaut de Schotten, Michel; Foulon, Chris; Rosso, Charlotte; Clarençon, Frédéric; Dupont, Sophie; Pradat-Diehl, Pascale; Labeyrie, Marc-Antoine; Levy, Richard; Volle, Emmanuelle

    2016-06-01

    SEE BURGESS DOI101093/BRAIN/AWW092 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : Analogical reasoning is at the core of the generalization and abstraction processes that enable concept formation and creativity. The impact of neurological diseases on analogical reasoning is poorly known, despite its importance in everyday life and in society. Neuroimaging studies of healthy subjects and the few studies that have been performed on patients have highlighted the importance of the prefrontal cortex in analogical reasoning. However, the critical cerebral bases for analogical reasoning deficits remain elusive. In the current study, we examined analogical reasoning abilities in 27 patients with focal damage in the frontal lobes and performed voxel-based lesion-behaviour mapping and tractography analyses to investigate the structures critical for analogical reasoning. The findings revealed that damage to the left rostrolateral prefrontal region (or some of its long-range connections) specifically impaired the ability to reason by analogies. A short version of the analogy task predicted the existence of a left rostrolateral prefrontal lesion with good accuracy. Experimental manipulations of the analogy tasks suggested that this region plays a role in relational matching or integration. The current lesion approach demonstrated that the left rostrolateral prefrontal region is a critical node in the analogy network. Our results also suggested that analogy tasks should be translated to clinical practice to refine the neuropsychological assessment of patients with frontal lobe lesions. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Frontopolar cortex mediates abstract integration in analogy.

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    Green, Adam E; Fugelsang, Jonathan A; Kraemer, David J M; Shamosh, Noah A; Dunbar, Kevin N

    2006-06-22

    Integration of abstractly similar relations during analogical reasoning was investigated using functional magnetic resonance imaging. Activation elicited by an analogical reasoning task that required both complex working memory and integration of abstractly similar relations was compared to activation elicited by a non-analogical task that required complex working memory in the absence of abstract relational integration. A left-sided region of the frontal pole of the brain (BA 9/10) was selectively active for the abstract relational integration component of analogical reasoning. Analogical reasoning also engaged a left-sided network of parieto-frontal regions. Activity in this network during analogical reasoning is hypothesized to reflect categorical alignment of individual component terms that make up analogies. This parieto-frontal network was also engaged by the complex control task, which involved explicit categorization, but not by a simpler control task, which did not involve categorization. We hypothesize that frontopolar cortex mediates abstract relational integration in complex reasoning while parieto-frontal regions mediate working memory processes, including manipulation of terms for the purpose of categorical alignment, that facilitate this integration.

  6. Altered SPECT 123I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa

    Science.gov (United States)

    Nagamitsu, Shinichiro; Sakurai, Rieko; Matsuoka, Michiko; Chiba, Hiromi; Ozono, Shuichi; Tanigawa, Hitoshi; Yamashita, Yushiro; Kaida, Hayato; Ishibashi, Masatoshi; Kakuma, Tatsuki; Croarkin, Paul E.; Matsuishi, Toyojiro

    2016-01-01

    Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using 123I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). “Depression–Dejection” and “Confusion” POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered

  7. Body frontal area in passerine birds

    OpenAIRE

    Hedenström, Anders; Rosén, Mikael

    2003-01-01

    Projected body frontal area is used when estimating the parasite drag of bird flight. We investigated the relationship between projected frontal area and body mass among passerine birds, and compared it with an equation based on waterfowl and raptors, which is used as default procedure in a widespread software package for flight performance calculations. The allometric equation based on waterfowl/raptors underestimates the frontal area compared to the passerine equation presented here. Conseq...

  8. It's not what you say, but how you say it: a reciprocal temporo-frontal network for affective prosody

    Directory of Open Access Journals (Sweden)

    David I Leitman

    2010-02-01

    Full Text Available Humans communicate emotion vocally by modulating acoustic cues such as pitch, intensity and voice quality. Research has documented how the relative presence or absence of such cues alters the likelihood of perceiving an emotion, but the neural underpinnings of acoustic cue-dependent emotion perception remain obscure. Using functional magnetic resonance imaging in 20 subjects we examined a reciprocal circuit consisting of superior temporal cortex, amygdala and inferior frontal gyrus that may underlie affective prosodic comprehension. Results showed that increased saliency of emotion-specific acoustic cues was associated with increased activation in superior temporal cortex (planum temporale (PT, posterior superior temporal gyrus (pSTG, and posterior superior middle gyrus (pMTG and amygdala, whereas decreased saliency of acoustic cues was associated with increased inferior frontal activity and temporo-frontal connectivity. These results suggest that sensory-integrative processing is facilitated when the acoustic signal is rich in affective information, yielding increased activation in temporal cortex and amygdala. Conversely, when the acoustic signal is ambiguous, greater evaluative processes are recruited, increasing activation in inferior frontal gyrus (IFG and IFG STG connectivity. Auditory regions may thus integrate acoustic information with amygdala input to form emotion-specific representations, which are evaluated within inferior frontal regions.

  9. Orbitofrontal cortex biases attention to emotional events.

    Science.gov (United States)

    Hartikainen, Kaisa M; Ogawa, Keith H; Knight, Robert T

    2012-01-01

    We examined the role of orbitofrontal (OF) cortex in regulating emotion-attention interaction and the balance between involuntary and voluntary attention allocation. We studied patients with OF lesion applying reaction time (RT) and event-related potential (ERP) measures in a lateralized visual discrimination task with novel task-irrelevant affective pictures (unpleasant, pleasant, or neutral) preceding a neutral target. This