Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

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Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

2014-06-01

The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Human Thalamic-Prefrontal Peduncle Connectivity Revealed by Diffusion Spectrum Imaging Fiber Tracking

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Chuanqi Sun

2018-04-01

Full Text Available The thalamic-prefrontal peduncle (TPP is a large bundle connecting the thalamus and prefrontal cortex. The definitive structure and function of the TPP are still controversial. To investigate the connectivity and segmentation patterns of the TPP, we employed diffusion spectrum imaging with generalized q-sampling reconstruction to perform both subject-specific and template-based analyses. Our results confirmed the trajectory and spatial relationship of the TPP in the human brain and identified the connection areas in the prefrontal cortex. The TPP-connecting areas identified based on Brodmann areas (BAs were BAs 8–11 and 45–47. Based on the automated anatomical atlas, these areas were the medial superior frontal gyrus, superior frontal gyrus, middle frontal gyrus, pars triangularis, pars orbitalis, anterior orbital gyrus, and lateral orbital gyrus. In addition, we identified the TPP connection areas in the thalamus, including the anterior and medial nuclei, and the lateral dorsal/lateral posterior nuclei. TPP fibers connected the thalamus with the ipsilateral prefrontal BAs 11, 47, 10, 46, 45, 9, and 8 seriatim from medial to lateral, layer by layer. Our results provide further details of the thalamic-prefrontal peduncle structure, and may aid future studies and a better understanding of the functional roles of the TPP in the human brain.

Interplay of hippocampus and prefrontal cortex in memory

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Preston, Alison R.; Eichenbaum, Howard

2013-01-01

Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

Increased functional connectivity between prefrontal cortex and reward system in pathological gambling.

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Saskia Koehler

Full Text Available Pathological gambling (PG shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum. PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

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Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

2017-10-01

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

Alpha, beta and gamma electrocorticographic rhythms in somatosensory, motor, premotor and prefrontal cortical areas differ in movement execution and observation in humans.

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Babiloni, Claudio; Del Percio, Claudio; Vecchio, Fabrizio; Sebastiano, Fabio; Di Gennaro, Giancarlo; Quarato, Pier P; Morace, Roberta; Pavone, Luigi; Soricelli, Andrea; Noce, Giuseppe; Esposito, Vincenzo; Rossini, Paolo Maria; Gallese, Vittorio; Mirabella, Giovanni

2016-01-01

In the present study, we tested the hypothesis that both movement execution and observation induce parallel modulations of alpha, beta, and gamma electrocorticographic (ECoG) rhythms in primary somatosensory (Brodmann area 1-2, BA1-2), primary motor (BA4), ventral premotor (BA6), and prefrontal (BA44 and BA45, part of putative human mirror neuron system underlying the understanding of actions of other people) areas. ECoG activity was recorded in drug-resistant epileptic patients during the execution of actions to reach and grasp common objects according to their affordances, as well as during the observation of the same actions performed by an experimenter. Both action execution and observation induced a desynchronization of alpha and beta rhythms in BA1-2, BA4, BA6, BA44 and BA45, which was generally higher in amplitude during the former than the latter condition. Action execution also induced a major synchronization of gamma rhythms in BA4 and BA6, again more during the execution of an action than during its observation. Human primary sensorimotor, premotor, and prefrontal areas do generate alpha, beta, and gamma rhythms and differently modulate them during action execution and observation. Gamma rhythms of motor areas are especially involved in action execution. Oscillatory activity of neural populations in sensorimotor, premotor and prefrontal (part of human mirror neuron system) areas represents and distinguishes own actions from those of other people. This methodological approach might be used for a neurophysiological diagnostic imaging of social cognition in epileptic patients. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder.

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Buchsbaum, Monte S; Nenadic, Igor; Hazlett, Erin A; Spiegel-Cohen, Jacqueline; Fleischman, Michael B; Akhavan, Arash; Silverman, Jeremy M; Siever, Larry J

2002-03-01

In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients.

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex.

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Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-07-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. © The Author (2017). Published by Oxford University Press.

From sensorimotor learning to memory cells in prefrontal and temporal association cortex: a neurocomputational study of disembodiment.

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Pulvermüller, Friedemann; Garagnani, Max

2014-08-01

Memory cells, the ultimate neurobiological substrates of working memory, remain active for several seconds and are most commonly found in prefrontal cortex and higher multisensory areas. However, if correlated activity in "embodied" sensorimotor systems underlies the formation of memory traces, why should memory cells emerge in areas distant from their antecedent activations in sensorimotor areas, thus leading to "disembodiment" (movement away from sensorimotor systems) of memory mechanisms? We modelled the formation of memory circuits in six-area neurocomputational architectures, implementing motor and sensory primary, secondary and higher association areas in frontotemporal cortices along with known between-area neuroanatomical connections. Sensorimotor learning driven by Hebbian neuroplasticity led to formation of cell assemblies distributed across the different areas of the network. These action-perception circuits (APCs) ignited fully when stimulated, thus providing a neural basis for long-term memory (LTM) of sensorimotor information linked by learning. Subsequent to ignition, activity vanished rapidly from APC neurons in sensorimotor areas but persisted in those in multimodal prefrontal and temporal areas. Such persistent activity provides a mechanism for working memory for actions, perceptions and symbols, including short-term phonological and semantic storage. Cell assembly ignition and "disembodied" working memory retreat of activity to multimodal areas are documented in the neurocomputational models' activity dynamics, at the level of single cells, circuits, and cortical areas. Memory disembodiment is explained neuromechanistically by APC formation and structural neuroanatomical features of the model networks, especially the central role of multimodal prefrontal and temporal cortices in bridging between sensory and motor areas. These simulations answer the "where" question of cortical working memory in terms of distributed APCs and their inner structure

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

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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.

Changes in self-regulation-related prefrontal activities in eating disorders: a near infrared spectroscopy study.

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Chihiro Sutoh

Full Text Available OBJECTIVE: The aim of this study is to clarify the symptomatology of the eating disorders examining the prefrontal function and activity associated with self-regulation among participants with or without eating disorders. METHODS: Ten patients with anorexia nervosa, fourteen with bulimia nervosa, and fourteen healthy control participants performed two cognitive tasks assessing self-regulatory functions, an auditorily distracted word fluency task and a rock-paper-scissors task under the measurements on prefrontal oxyhemoglobin concentration with near infrared spectroscopy. The psychiatric symptoms of patient groups were assessed with several questionnaires. RESULTS: Patients with bulimia nervosa showed decreased performances and prefrontal hyper activation patterns. Prefrontal activities showed a moderate negative correlation with task performances not in the patient groups but only in the healthy participants. The prefrontal activities of the patient groups showed positive correlations with some symptom scale aspects. CONCLUSIONS: The decreased cognitive abilities and characteristic prefrontal activation patterns associated with self-regulatory functions were shown in patients with bulimia nervosa, which correlated with their symptoms. These findings suggest inefficient prefrontal self-regulatory function of bulimia nervosa that associate with its symptoms.

Enhanced Operant Extinction and Prefrontal Excitability in a Mouse Model of Angelman Syndrome.

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Sidorov, Michael S; Judson, Matthew C; Kim, Hyojin; Rougie, Marie; Ferrer, Alejandra I; Nikolova, Viktoriya D; Riddick, Natallia V; Moy, Sheryl S; Philpot, Benjamin D

2018-03-14

Angelman syndrome (AS), a neurodevelopmental disorder associated with intellectual disability, is caused by loss of maternal allele expression of UBE3A in neurons. Mouse models of AS faithfully recapitulate disease phenotypes across multiple domains, including behavior. Yet in AS, there has been only limited study of behaviors encoded by the prefrontal cortex, a region broadly involved in executive function and cognition. Because cognitive impairment is a core feature of AS, it is critical to develop behavioral readouts of prefrontal circuit function in AS mouse models. One such readout is behavioral extinction, which has been well described mechanistically and relies upon prefrontal circuits in rodents. Here we report exaggerated operant extinction in male AS model mice, concomitant with enhanced excitability in medial prefrontal neurons from male and female AS model mice. Abnormal behavior was specific to operant extinction, as two other prefrontally dependent tasks (cued fear extinction and visuospatial discrimination) were largely normal in AS model mice. Inducible deletion of Ube3a during adulthood was not sufficient to drive abnormal extinction, supporting the hypothesis that there is an early critical period for development of cognitive phenotypes in AS. This work represents the first formal experimental analysis of prefrontal circuit function in AS, and identifies operant extinction as a useful experimental paradigm for modeling cognitive aspects of AS in mice. SIGNIFICANCE STATEMENT Prefrontal cortex encodes "high-level" cognitive processes. Thus, understanding prefrontal function is critical in neurodevelopmental disorders where cognitive impairment is highly penetrant. Angelman syndrome is a neurodevelopmental disorder associated with speech and motor impairments, an outwardly happy demeanor, and intellectual disability. We describe a behavioral phenotype in a mouse model of Angelman syndrome and related abnormalities in prefrontal cortex function. We

Arrested development: early prefrontal lesions impair the maturation of moral judgement.

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Taber-Thomas, Bradley C; Asp, Erik W; Koenigs, Michael; Sutterer, Matthew; Anderson, Steven W; Tranel, Daniel

2014-04-01

Learning to make moral judgements based on considerations beyond self-interest is a fundamental aspect of moral development. A deficit in such learning is associated with poor socialization and criminal behaviour. The neural systems required for the acquisition and maturation of moral competency are not well understood. Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement. In response to simple hypothetical moral scenarios, the patients were more likely than comparison participants to endorse self-interested actions that involved breaking moral rules or physically harming others in order to benefit themselves. This pattern (which we also found in subjects with psychopathy) differs from that of patients with adult-onset ventromedial prefrontal cortex lesions--the latter group showed normal rejection of egocentric rule violations. This novel contrast of patients with ventromedial prefrontal cortex lesions acquired during development versus during adulthood yields new evidence suggesting that the ventromedial prefrontal cortex is a critical neural substrate for the acquisition and maturation of moral competency that goes beyond self-interest to consider the welfare of others. Disruption to this affective neural system early in life interrupts moral development.

[Neurobiological aspects of personality disorders and emotional instability].

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Petrovic, Predrag

2016-12-06

Neurobiological aspects of personality disorders and emotional instability ADHD and mental disorders encompassing emotional instability such as emotionally unstable personality disorder and antisocial personality disorder can potentially be explained by a suboptimal regulation of information processing in the brain. ADHD involves suboptimal function of non-emotional attentional regulatory processes and emotional instability involves suboptimal emotional regulation. A network including prefrontal areas, anterior cingulate cortex, basal ganglia and specific neuromodulatory systems such as the dopamine system are dysfunctional in both ADHD and emotional instability. One might suggest that a dimensional view better describes these mental states than categorical diagnoses.

The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive.

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Goldman-Rakic, P S

1996-10-29

The functional architecture of prefrontal cortex is central to our understanding of human mentation and cognitive prowess. This region of the brain is often treated as an undifferentiated structure, on the one hand, or as a mosaic of psychological faculties, on the other. This paper focuses on the working memory processor as a specialization of prefrontal cortex and argues that the different areas within prefrontal cortex represent iterations of this function for different information domains, including spatial cognition, object cognition and additionally, in humans, semantic processing. According to this parallel processing architecture, the 'central executive' could be considered an emergent property of multiple domain-specific processors operating interactively. These processors are specializations of different prefrontal cortical areas, each interconnected both with the domain-relevant long-term storage sites in posterior regions of the cortex and with appropriate output pathways.

Area-specific information processing in prefrontal cortex during a probabilistic inference task: a multivariate fMRI BOLD time series analysis.

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Charmaine Demanuele

Full Text Available Discriminating spatiotemporal stages of information processing involved in complex cognitive processes remains a challenge for neuroscience. This is especially so in prefrontal cortex whose subregions, such as the dorsolateral prefrontal (DLPFC, anterior cingulate (ACC and orbitofrontal (OFC cortices are known to have differentiable roles in cognition. Yet it is much less clear how these subregions contribute to different cognitive processes required by a given task. To investigate this, we use functional MRI data recorded from a group of healthy adults during a "Jumping to Conclusions" probabilistic reasoning task.We used a novel approach combining multivariate test statistics with bootstrap-based procedures to discriminate between different task stages reflected in the fMRI blood oxygenation level dependent signal pattern and to unravel differences in task-related information encoded by these regions. Furthermore, we implemented a new feature extraction algorithm that selects voxels from any set of brain regions that are jointly maximally predictive about specific task stages.Using both the multivariate statistics approach and the algorithm that searches for maximally informative voxels we show that during the Jumping to Conclusions task, the DLPFC and ACC contribute more to the decision making phase comprising the accumulation of evidence and probabilistic reasoning, while the OFC is more involved in choice evaluation and uncertainty feedback. Moreover, we show that in presumably non-task-related regions (temporal cortices all information there was about task processing could be extracted from just one voxel (indicating the unspecific nature of that information, while for prefrontal areas a wider multivariate pattern of activity was maximally informative.We present a new approach to reveal the different roles of brain regions during the processing of one task from multivariate activity patterns measured by fMRI. This method can be a valuable

Influence of restoration adjustments on prefrontal blood flow: A simplified NIRS preliminary study.

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Sasaguri, Kenichi; Otsuka, Takero; Tsunashima, Hiroyuki; Shimazaki, Tateshi; Kubo, Kin-Ya; Onozuka, Minoru

The aim of this study was to examine, after setting several restorations, the influence of adjusted occlusal interference during gum chewing on blood flow in the prefrontal area as determined using near-infrared spectroscopy. The physiological rate was assessed using a visual analog scale (VAS) questionnaire. We selected 16 patients who desired prosthetic restorative treatment on the lateral dentition, and eight healthy volunteers. Subjects were divided into three eight-person groups. One group received restorations on the premolar area (PA), another group received restorations on the molar area (MA), and the control group (CT) received no prosthetic restorations. The spectroscope was fastened to the frontal region of the head after placement of the final restoration, but before adjustment. Pre-adjustment (first gum chewing for CT) blood flow in the prefrontal cortex was measured during gum chewing. Blood flow was again measured during gum chewing after the restoration (second gum chewing for CT) had been adjusted in accordance with the subjective assessment of the patient while wearing the device. The VAS provided quantification of comfort during gum chewing before and after restoration adjustment. For the PA and MA groups, adjusting restorations decreased discomfort significantly during gum chewing. Moreover, in the MA group, prefrontal blood flow was significantly reduced, and blood flow correlated with discomfort. Activation of the prefrontal area may provide an objective criterion for judging the functionality of occlusion after prosthetic occlusal reconstruction and/or orthodontics.

Effects of prefrontal cortical inactivation on neural activity in the ventral tegmental area

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Jo, Yong Sang; Lee, Jane; Mizumori, Sheri J.Y.

2013-01-01

Dopamine (DA) cells have been suggested to signal discrepancies between expected and actual rewards in reinforcement learning. DA cells in the ventral tegmental area (VTA) receive direct projections from the medial prefrontal cortex (mPFC), a structure that is known as one of the brain areas that represent expected future rewards. To investigate whether the mPFC contributes to generating reward prediction error signals of DA cells, we recorded VTA cells from rats foraging for different amounts of reward in a spatial working memory task. Our results showed that DA cells initially responded after the acquisition of rewards, but over training, they exhibited phasic responses when rats detected sensory cues originating from the rewards before obtaining them. We also observed two separate groups of non-DA cells that were activated in expectation of upcoming rewards or during reward consumption. Bilateral injections of muscimol, a GABAA agonist, into the mPFC significantly decreased the non-DA activity that encoded reward expectation. By contrast, the same manipulation of the mPFC elevated DA responses to reward-predicting cues. However, neither DA nor non-DA responses that were elicited after reward acquisition were affected by mPFC inactivation. These results suggest that the mPFC provides the information about expected rewards to the VTA, and its functional loss elevates DA responses to reward-predicting cues by altering expectations about forthcoming rewards. PMID:23658156

Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.

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Tse, Maric T; Piantadosi, Patrick T; Floresco, Stan B

2015-06-01

Cognitive dysfunction in schizophrenia is one of the most pervasive and debilitating aspects of the disorder. Among the numerous neural abnormalities that may contribute to schizophrenia symptoms, perturbations in markers for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), particularly within the frontal lobes, are some of the most reliable alterations observed at postmortem examination. However, how prefrontal GABA dysfunction contributes to cognitive impairment in schizophrenia remains unclear. We provide an overview of postmortem GABAergic perturbations in the brain affected by schizophrenia and describe circumstantial evidence linking these alterations to cognitive dysfunction. In addition, we conduct a survey of studies using neurodevelopmental, genetic, and pharmacologic rodent models that induce schizophrenia-like cognitive impairments, highlighting the convergence of these mechanistically distinct approaches to prefrontal GABAergic disruption. We review preclinical studies that have directly targeted prefrontal cortical GABAergic transmission using local application of GABAA receptor antagonists. These studies have provided an important link between GABA transmission and cognitive dysfunction in schizophrenia because they show that reducing prefrontal inhibitory transmission induces various cognitive, emotional, and dopaminergic abnormalities that resemble aspects of the disorder. These converging clinical and preclinical findings provide strong support for the idea that perturbations in GABA signaling drive certain forms of cognitive dysfunction in schizophrenia. Future studies using this approach will yield information to refine further a putative "GABA hypothesis" of schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The prefrontal cortex: insights from functional neuroimaging using cognitive activation tasks

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Goethals, Ingeborg; Van de Wiele, Christophe; Dierckx, Rudi [Division of Nuclear Medicine, Polikliniek 7, Ghent University Hospital, De Pintelaan 185, 9000, Ghent (Belgium); Audenaert, Kurt [Department of Psychiatry and Medical Psychology, Ghent University Hospital, Ghent (Belgium)

2004-03-01

This review presents neuroimaging studies which have explored the functional anatomy of a variety of cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies have demonstrated that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain of which the PFC consistently forms a part. As such, these results are in keeping with the notion that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain regions in a large number of different executive tasks suggests that higher-level cognitive functions may best be understood in terms of an interactive network of specialised anterior as well as posterior brain regions. (orig.)

The prefrontal cortex: insights from functional neuroimaging using cognitive activation tasks

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Goethals, Ingeborg; Van de Wiele, Christophe; Dierckx, Rudi; Audenaert, Kurt

2004-01-01

This review presents neuroimaging studies which have explored the functional anatomy of a variety of cognitive processes represented by the prefrontal cortex (PFC). Overall, these studies have demonstrated that standard prefrontal neuroactivation tasks recruit a widely distributed network within the brain of which the PFC consistently forms a part. As such, these results are in keeping with the notion that executive functions within the PFC rely not only on anterior (mainly prefrontal) brain areas, but also on posterior (mainly parietal) brain regions. Moreover, intervention of similar brain regions in a large number of different executive tasks suggests that higher-level cognitive functions may best be understood in terms of an interactive network of specialised anterior as well as posterior brain regions. (orig.)

Prefrontal Cortex, Emotion, and Approach/Withdrawal Motivation.

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Spielberg, Jeffrey M; Stewart, Jennifer L; Levin, Rebecca L; Miller, Gregory A; Heller, Wendy

2008-01-01

This article provides a selective review of the literature and current theories regarding the role of prefrontal cortex, along with some other critical brain regions, in emotion and motivation. Seemingly contradictory findings have often appeared in this literature. Research attempting to resolve these contradictions has been the basis of new areas of growth and has led to more sophisticated understandings of emotional and motivational processes as well as neural networks associated with these processes. Progress has, in part, depended on methodological advances that allow for increased resolution in brain imaging. A number of issues are currently in play, among them the role of prefrontal cortex in emotional or motivational processes. This debate fosters research that will likely lead to further refinement of conceptualizations of emotion, motivation, and the neural processes associated with them.

Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex.

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Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun

2016-06-15

Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of (stereotactic) parcellations in mouse prefrontal cortex

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van de Werd, H.J.J.M.; Uylings, H.B.M.

2014-01-01

This study compares the cytoarchitectonic parcellation of the prefrontal cortex (PFC) in the mouse as presented in publications that are commonly used for identifying brain areas. Agreement was found to be greater for boundaries in the medial PFC than in the lateral PFC and lowest for those in the

Anatomical segmentation of the human medial prefrontal cortex

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Corcoles-Parada, M.; Müller, N.C.J.; Ubero, M.; Serrano-Del-Pueblo, V.M.; Mansilla, F.; Marcos-Rabal, P.; Artacho-Perula, E.; Dresler, M.; Insausti, R.; Fernandez, G.; Munoz-Lopez, M.

2017-01-01

The medial prefrontal areas 32, 24, 14, and 25 (mPFC) form part of the limbic memory system, but little is known about their functional specialization in humans. To add anatomical precision to structural and functional magnetic resonance imaging (MRI) data, we aimed to identify these mPFC subareas

Disrupted thalamic prefrontal pathways in patients with idiopathic dystonia

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Bonilha, Leonardo; de Vries, Paulien M.; Hurd, Mark W.; Rorden, Chris; Morgan, Paul S.; Besenski, Nada; Bergmann, Kenneth J.; Hinson, Vanessa K.

There are quantifiable abnormalities in water diffusion properties of the white matter in thalamic and prefrontal areas in patients with idiopathic dystonia (ID). However, it is unclear which pathways are disrupted in these patients. Using probabilistic tractography of high resolution DTI, we

Capacity-speed relationships in prefrontal cortex.

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Vivek Prabhakaran

Full Text Available Working memory (WM capacity and WM processing speed are simple cognitive measures that underlie human performance in complex processes such as reasoning and language comprehension. These cognitive measures have shown to be interrelated in behavioral studies, yet the neural mechanism behind this interdependence has not been elucidated. We have carried out two functional MRI studies to separately identify brain regions involved in capacity and speed. Experiment 1, using a block-design WM verbal task, identified increased WM capacity with increased activity in right prefrontal regions, and Experiment 2, using a single-trial WM verbal task, identified increased WM processing speed with increased activity in similar regions. Our results suggest that right prefrontal areas may be a common region interlinking these two cognitive measures. Moreover, an overlap analysis with regions associated with binding or chunking suggest that this strategic memory consolidation process may be the mechanism interlinking WM capacity and WM speed.

ASPECTS REGARDING AIR QUALITY IN DEVA AREA

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CARMEN DRAGOTA

2012-03-01

Full Text Available Aspects regarding air quality in Deva area. The attenuation of air quality in the urban environment is determined by artificial warming, a result of the radiation emitted by constructions, economic activities, as well as the climatic elements characteristics. In the survey regarding air quality in Deva we will analyse the concentrations of NO2, O3, SO2 and their implications on air quality.

Agricultural in protect areas: agronomic aspects

Directory of Open Access Journals (Sweden)

Emanuele Tarantino

Full Text Available Among the various aims of the protect lands, as expressed by the art. 1 of the L. 394/91, there is “the promotion of educational, formative, experimental and interdisciplinary activities, as well as recreational activities”. Considering the multiplicity of the protect areas functions as well as the interests and the problems involved in their management, the most suitable research in this field is that according to a “systemic” approach. It concerns the study of the most high hierarchical levels: agricultural, farming and agro-territorial levels. The researches regard not only the environmental sustainability of crops production, including the control of the erosion risks and the management of the pasturing areas, but also other aspects that result less conventional than the classical questions of the Agronomy. They include the land planning, the productions of local and typical markets, the production dependent on the organic farming on the environmental preservation, the management of areas which result of particular interest for wild fauna, the renaturalization of degraded areas, the eco-sustainable management of water resources, the multifunctional agriculture, the landscape improvement and the biodiversity enhancement.

Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

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Schubert, D; Martens, G J M; Kolk, S M

2015-07-01

The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies.

Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

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Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

2016-07-01

Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms.

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Müller-Vahl, Kirsten R; Grosskreutz, Julian; Prell, Tino; Kaufmann, Jörn; Bodammer, Nils; Peschel, Thomas

2014-01-07

Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS "only" (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.

[Brodmann Areas 11, 46, and 47: Emotion, Memory, and Empathy].

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Ueda, Keita; Fujimoto, Gaku; Ubukata, Shiho; Murai, Toshiya

2017-04-01

Brodmann area 11 is one of the main constituent of the orbitofrontal cortex, and area 46 is that of the dorsolateral prefrontal cortex. The main function of Brodmann area 11 is the processing of emotion and value, whereas the main function of Brodmann area 46 is the processing of cognitive information, including working memory. In comparison, the function of area 47 is more complex. This area is related to the feeling of empathy towards the story contents of others, which is thought to be the emotional aspect of this area, while this area is also activated during automated action. This is in contrast with the function of area 46, which is involved in willed action. In addition, area 47 in the left hemisphere plays an important role in syntax processing.

Prefrontal cortex modulates desire and dread generated by nucleus accumbens glutamate disruption.

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Richard, Jocelyn M; Berridge, Kent C

2013-02-15

Corticolimbic circuits, including direct projections from prefrontal cortex to nucleus accumbens (NAc), permit top-down control of intense motivations generated by subcortical circuits. In rats, localized disruptions of glutamate signaling within medial shell of NAc generate desire or dread, anatomically organized along a rostrocaudal gradient analogous to a limbic keyboard. At rostral locations in shell, these disruptions generate appetitive eating, but at caudal locations the disruptions generate progressively fearful behaviors (distress vocalizations, escape attempts, and antipredator reactions). Here, we asked whether medial prefrontal cortex can modulate intense motivations generated by subcortical NAc disruptions. We used simultaneous microinjections in medial prefrontal cortex regions and in NAc shell to examine whether the desire or dread generated by NAc shell disruptions is modulated by activation/inhibition of three specific regions of prefrontal cortex: medial orbitofrontal cortex, infralimbic cortex (homologous to area 25 or subgenual anterior cingulate in the human), or prelimbic cortex (midventral anterior cingulate). We found that activation of medial orbitofrontal cortex biased intense bivalent motivation in an appetitive direction by amplifying generation of eating behavior by middle to caudal NAc disruptions, without altering fear. In contrast, activation of infralimbic prefrontal cortex powerfully and generally suppressed both appetitive eating and fearful behaviors generated by NAc shell disruptions. These results suggest that corticolimbic projections from discrete prefrontal regions can either bias motivational valence or generally suppress subcortically generated intense motivations of desire or fear. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Comparison of visual receptive fields in the dorsolateral prefrontal cortex and ventral intraparietal area in macaques.

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Viswanathan, Pooja; Nieder, Andreas

2017-12-01

The concept of receptive field (RF) describes the responsiveness of neurons to sensory space. Neurons in the primate association cortices have long been known to be spatially selective but a detailed characterisation and direct comparison of RFs between frontal and parietal association cortices are missing. We sampled the RFs of a large number of neurons from two interconnected areas of the frontal and parietal lobes, the dorsolateral prefrontal cortex (dlPFC) and ventral intraparietal area (VIP), of rhesus monkeys by systematically presenting a moving bar during passive fixation. We found that more than half of neurons in both areas showed spatial selectivity. Single neurons in both areas could be assigned to five classes according to the spatial response patterns: few non-uniform RFs with multiple discrete response maxima could be dissociated from the vast majority of uniform RFs showing a single maximum; the latter were further classified into full-field and confined foveal, contralateral and ipsilateral RFs. Neurons in dlPFC showed a preference for the contralateral visual space and collectively encoded the contralateral visual hemi-field. In contrast, VIP neurons preferred central locations, predominantly covering the foveal visual space. Putative pyramidal cells with broad-spiking waveforms in PFC had smaller RFs than putative interneurons showing narrow-spiking waveforms, but distributed similarly across the visual field. In VIP, however, both putative pyramidal cells and interneurons had similar RFs at similar eccentricities. We provide a first, thorough characterisation of visual RFs in two reciprocally connected areas of a fronto-parietal cortical network. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Social cognition in patients following surgery to the prefrontal cortex

NARCIS (Netherlands)

Jenkins, L.M.; Andrewes, D.G.; Nicholas, C.L.; Drummond, K.J.; Moffat, B.A.; Phal, P.; Desmond, P.; Kessels, R.P.C.

2014-01-01

Impaired social cognition, including emotion recognition, may explain dysfunctional emotional and social behaviour in patients with lesions to the ventromedial prefrontal cortex (VMPFC). However, the VMPFC is a large, poorly defined area that can be sub-divided into orbital and medial sectors. We

Interactive effects of music and prefrontal cortex stimulation in modulating response inhibition

OpenAIRE

Mansouri, Farshad Alizadeh; Acevedo, Nicola; Illipparampil, Rosin; Fehring, Daniel J.; Fitzgerald, Paul B.; Jaberzadeh, Shapour

2017-01-01

Influential hypotheses propose that alterations in emotional state influence decision processes and executive control of behavior. Both music and transcranial direct current stimulation (tDCS) of prefrontal cortex affect emotional state, however interactive effects of music and tDCS on executive functions remain unknown. Learning to inhibit inappropriate responses is an important aspect of executive control which is guided by assessing the decision outcomes such as errors. We found that high-...

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms

Science.gov (United States)

2014-01-01

Background Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS “only” (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Results Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Conclusions Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded. PMID:24397347

Increased neuronal firing in resting and sleep in areas of the macaque medial prefrontal cortex.

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Gabbott, Paul L; Rolls, Edmund T

2013-06-01

The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of the default mode network and is a brain region that shows increased activation in the resting state. A previous paper from our laboratory reported significantly increased firing rates of neurons in the macaque subgenual cingulate cortex, Brodmann area (BA) 25, during disengagement from a task and also during slow wave sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report the finding that there are neurons in other areas of mPFC that also increase their firing rates during disengagement from a task, drowsiness and eye-closure. During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9, 10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were identified whose firing rates altered significantly with eye-closure compared with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of the total population) significantly increased (mean + 329%; P ≪ 0.01) their average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2 spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P areas of mPFC, implicated in the anterior default mode network, there is a substantial population of neurons that significantly increase their firing rates during periods of eye-closure. Such neurons may be part of an interconnected network of distributed brain regions that are more active during periods of relaxed wakefulness than during attention-demanding tasks. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

fNIRS evidence of prefrontal regulation of frustration in early childhood.

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Perlman, Susan B; Luna, Beatriz; Hein, Tyler C; Huppert, Theodore J

2014-01-15

The experience of frustration is common in early childhood, yet some children seem to possess a lower tolerance for frustration than others. Characterizing the biological mechanisms underlying a wide range of frustration tolerance observed in early childhood may inform maladaptive behavior and psychopathology that is associated with this construct. The goal of this study was to measure prefrontal correlates of frustration in 3-5-year-old children, who are not readily adaptable for typical neuroimaging approaches, using functional near infrared spectroscopy (fNIRS). fNIRS of frontal regions were measured as frustration was induced in children through a computer game where a desired and expected prize was "stolen" by an animated dog. A fNIRS general linear model (GLM) was used to quantify the correlation of brain regions with the task and identify areas that were statistically different between the winning and frustrating test conditions. A second-level voxel-based ANOVA analysis was then used to correlate the amplitude of each individual's brain activation with measure of parent-reported frustration. Experimental results indicated increased activity in the middle prefrontal cortex during winning of a desired prize, while lateral prefrontal cortex activity increased during frustration. Further, activity increase in lateral prefrontal cortex during frustration correlated positively with parent-reported frustration tolerance. These findings point to the role of the lateral prefrontal cortex as a potential region supporting the regulation of emotion during frustration. Copyright © 2013 Elsevier Inc. All rights reserved.

MRI volumetry of prefrontal cortex

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Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

1995-05-01

Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

Working Memory in the Prefrontal Cortex

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Funahashi, Shintaro

2017-01-01

The prefrontal cortex participates in a variety of higher cognitive functions. The concept of working memory is now widely used to understand prefrontal functions. Neurophysiological studies have revealed that stimulus-selective delay-period activity is a neural correlate of the mechanism for temporarily maintaining information in working memory processes. The central executive, which is the master component of Baddeley’s working memory model and is thought to be a function of the prefrontal cortex, controls the performance of other components by allocating a limited capacity of memory resource to each component based on its demand. Recent neurophysiological studies have attempted to reveal how prefrontal neurons achieve the functions of the central executive. For example, the neural mechanisms of memory control have been examined using the interference effect in a dual-task paradigm. It has been shown that this interference effect is caused by the competitive and overloaded recruitment of overlapping neural populations in the prefrontal cortex by two concurrent tasks and that the information-processing capacity of a single neuron is limited to a fixed level, can be flexibly allocated or reallocated between two concurrent tasks based on their needs, and enhances behavioral performance when its allocation to one task is increased. Further, a metamemory task requiring spatial information has been used to understand the neural mechanism for monitoring its own operations, and it has been shown that monitoring the quality of spatial information represented by prefrontal activity is an important factor in the subject's choice and that the strength of spatially selective delay-period activity reflects confidence in decision-making. Although further studies are needed to elucidate how the prefrontal cortex controls memory resource and supervises other systems, some important mechanisms related to the central executive have been identified. PMID:28448453

Oscillations in the prefrontal cortex: a gateway to memory and attention.

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Benchenane, K.; Tiesinga, P.H.; Battaglia, F.P.

2011-01-01

We consider the potential role of oscillations in the prefrontal cortex (PFC) in mediating attention, working memory and memory consolidation. Activity in the theta, beta, and gamma bands is related to communication between PFC and different brain areas. While gamma/beta oscillations mediate

Connecting to create: expertise in musical improvisation is associated with increased functional connectivity between premotor and prefrontal areas.

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Pinho, Ana Luísa; de Manzano, Örjan; Fransson, Peter; Eriksson, Helene; Ullén, Fredrik

2014-04-30

Musicians have been used extensively to study neural correlates of long-term practice, but no studies have investigated the specific effects of training musical creativity. Here, we used human functional MRI to measure brain activity during improvisation in a sample of 39 professional pianists with varying backgrounds in classical and jazz piano playing. We found total hours of improvisation experience to be negatively associated with activity in frontoparietal executive cortical areas. In contrast, improvisation training was positively associated with functional connectivity of the bilateral dorsolateral prefrontal cortices, dorsal premotor cortices, and presupplementary areas. The effects were significant when controlling for hours of classical piano practice and age. These results indicate that even neural mechanisms involved in creative behaviors, which require a flexible online generation of novel and meaningful output, can be automated by training. Second, improvisational musical training can influence functional brain properties at a network level. We show that the greater functional connectivity seen in experienced improvisers may reflect a more efficient exchange of information within associative networks of importance for musical creativity.

Amodal processing in human prefrontal cortex.

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Tamber-Rosenau, Benjamin J; Dux, Paul E; Tombu, Michael N; Asplund, Christopher L; Marois, René

2013-07-10

Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex.

Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

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Nagy, Bernadett; Szabó, István; Papp, Szilárd; Takács, Gábor; Szalay, Csaba; Karádi, Zoltán

2012-03-20

The mediodorsal prefrontal cortex (mdPFC), a key structure of the limbic neural circuitry, plays important roles in the central regulation of feeding. As an integrant part of the forebrain dopamine (DA) system, it performs complex roles via interconnections with various brain areas where glucose-monitoring (GM) neurons have been identified. The main goal of the present experiments was to examine whether similar GM neurons exist in the mediodorsal prefrontal cortex. To search for such chemosensory cells here, and to estimate their involvement in the DA circuitry, extracellular single neuron activity of the mediodorsal prefrontal cortex of anesthetized Wistar and Sprague-Dawley rats was recorded by means of tungsten wire multibarreled glass microelectrodes during microelectrophoretic administration of d-glucose and DA. One fourth of the neurons tested changed in firing rate in response to glucose, thus, proved to be elements of the forebrain GM neural network. DA responsive neurons in the mdPFC were found to represent similar proportion of all cells; the glucose-excited units were shown to display excitatory whereas the glucose-inhibited neurons were demonstrated to exert mainly inhibitory responses to dopamine. The glucose-monitoring neurons of the mdPFC and their distinct DA sensitivity are suggested to be of particular significance in adaptive processes of the central feeding control. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of Rostral Prefrontal Cortex and Cognitive and Behavioural Disorders

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Dumontheil, Iroise; Burgess, Paul W.; Blakemore, Sarah-Jayne

2008-01-01

Information on the development and functions of rostral prefrontal cortex (PFC), or Brodmann area 10, has been gathered from different fields, from anatomical development to functional neuroimaging in adults, and put forward in relation to three particular cognitive and behavioural disorders. Rostral PFC is larger and has a lower cell density in…

Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

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Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

2011-03-01

Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Emotional and Utilitarian Appraisals of Moral Dilemmas Are Encoded in Separate Areas and Integrated in Ventromedial Prefrontal Cortex

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Montaser-Kouhsari, Leila; Woodward, James; Rangel, Antonio

2015-01-01

Moral judgment often requires making difficult tradeoffs (e.g., is it appropriate to torture to save the lives of innocents at risk?). Previous research suggests that both emotional appraisals and more deliberative utilitarian appraisals influence such judgments and that these appraisals often conflict. However, it is unclear how these different types of appraisals are represented in the brain, or how they are integrated into an overall moral judgment. We addressed these questions using an fMRI paradigm in which human subjects provide separate emotional and utilitarian appraisals for different potential actions, and then make difficult moral judgments constructed from combinations of these actions. We found that anterior cingulate, insula, and superior temporal gyrus correlated with emotional appraisals, whereas temporoparietal junction and dorsomedial prefrontal cortex correlated with utilitarian appraisals. Overall moral value judgments were represented in an anterior portion of the ventromedial prefrontal cortex. Critically, the pattern of responses and functional interactions between these three sets of regions are consistent with a model in which emotional and utilitarian appraisals are computed independently and in parallel, and passed to the ventromedial prefrontal cortex where they are integrated into an overall moral value judgment. SIGNIFICANCE STATEMENT Popular accounts of moral judgment often describe it as a battle for control between two systems, one intuitive and emotional, the other rational and utilitarian, engaged in winner-take-all inhibitory competition. Using a novel fMRI paradigm, we identified distinct neural signatures of emotional and utilitarian appraisals and used them to test different models of how they compete for the control of moral behavior. Importantly, we find little support for competitive inhibition accounts. Instead, moral judgments resembled the architecture of simple economic choices: distinct regions represented emotional

Preserved speech abilities and compensation following prefrontal damage.

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Buckner, R L; Corbetta, M; Schatz, J; Raichle, M E; Petersen, S E

1996-02-06

Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study.

Incremental rate of prefrontal oxygenation determines performance speed during cognitive Stroop test: the effect of ageing.

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Endo, Kana; Liang, Nan; Idesako, Mitsuhiro; Ishii, Kei; Matsukawa, Kanji

2018-02-19

Cognitive function declines with age. The underlying mechanisms responsible for the deterioration of cognitive performance, however, remain poorly understood. We hypothesized that an incremental rate of prefrontal oxygenation during a cognitive Stroop test decreases in progress of ageing, resulting in a slowdown of cognitive performance. To test this hypothesis, we identified, using multichannel near-infrared spectroscopy, the characteristics of the oxygenated-hemoglobin concentration (Oxy-Hb) responses of the prefrontal cortex to both incongruent Stroop and congruent word-reading test. Spatial distributions of the significant changes in the three components (initial slope, peak amplitude, and area under the curve) of the Oxy-Hb response were compared between young and elderly subjects. The Stroop interference time (as a difference in total periods for executing Stroop and word-reading test, respectively) approximately doubled in elderly as compared to young subjects. The Oxy-Hb in the rostrolateral, but not caudal, prefrontal cortex increased during the Stroop test in both age groups. The initial slope of the Oxy-Hb response, rather than the peak and area under the curve, had a strong correlation with cognitive performance speed. Taken together, it is likely that the incremental rate of prefrontal oxygenation may decrease in progress of ageing, resulting in a decline in cognitive performance.

Monkey prefrontal neurons during Sternberg task performance: full contents of working memory or most recent item?

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Konecky, R O; Smith, M A; Olson, C R

2017-06-01

To explore the brain mechanisms underlying multi-item working memory, we monitored the activity of neurons in the dorsolateral prefrontal cortex while macaque monkeys performed spatial and chromatic versions of a Sternberg working-memory task. Each trial required holding three sequentially presented samples in working memory so as to identify a subsequent probe matching one of them. The monkeys were able to recall all three samples at levels well above chance, exhibiting modest load and recency effects. Prefrontal neurons signaled the identity of each sample during the delay period immediately following its presentation. However, as each new sample was presented, the representation of antecedent samples became weak and shifted to an anomalous code. A linear classifier operating on the basis of population activity during the final delay period was able to perform at approximately the level of the monkeys on trials requiring recall of the third sample but showed a falloff in performance on trials requiring recall of the first or second sample much steeper than observed in the monkeys. We conclude that delay-period activity in the prefrontal cortex robustly represented only the most recent item. The monkeys apparently based performance of this classic working-memory task on some storage mechanism in addition to the prefrontal delay-period firing rate. Possibilities include delay-period activity in areas outside the prefrontal cortex and changes within the prefrontal cortex not manifest at the level of the firing rate. NEW & NOTEWORTHY It has long been thought that items held in working memory are encoded by delay-period activity in the dorsolateral prefrontal cortex. Here we describe evidence contrary to that view. In monkeys performing a serial multi-item working memory task, dorsolateral prefrontal neurons encode almost exclusively the identity of the sample presented most recently. Information about earlier samples must be encoded outside the prefrontal cortex or

Real-time monitoring prefrontal activities during online video game playing by functional near-infrared spectroscopy.

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Li, Yue; Zhang, Lei; Long, Kehong; Gong, Hui; Lei, Hao

2018-02-16

A growing body of literature has suggested that video game playing can induce functional and structural plasticity of the brain. The underlying mechanisms, however, remain poorly understood. In this study, functional near-infrared spectroscopy (fNIRS) was used to record prefrontal activities in 24 experienced game players when they played a massively multiplayer online battle arena video game, League of Legends (LOL), under naturalistic conditions. It was observed that game onset was associated with significant activations in the ventrolateral prefrontal cortex (VLPFC) and concomitant deactivations in the dorsolateral prefrontal cortex (DLPFC) and frontal pole area (FPA). Game events, such as slaying an enemy and being slain by an enemy evoked region-specific time-locked hemodynamic/oxygenation responses in the prefrontal cortex (PFC). It was proposed that the VLPFC activities during LOL playing are likely responses to visuo-motor task load of the game, while the DLPFC/FPA activities may be involved in the constant shifts of attentional states and allocation of cognitive resources required by game playing. The present study demonstrated that it is feasible to use fNIRS to monitor real-time prefrontal activity during online video game playing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of the Priority Aspect in Process of Determining Urban Residential Area

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Bhekti Pribadi, Cherie; Hariyanto, Teguh

2017-12-01

Recently, the population growth is increasingly crowded in urban area and as a source of land supply for housing development into the needs of each individual becomes increasingly limited. the home is one of the basic rights of the people and therefore every citizen has the right to reside and got a good environment and healthy. Besides the house is also a basic human need to enhance the dignity, the dignity, quality of life and livelihood, as well as personal self-reflection in order to improve the standard of living, as well as the formation of character, character and personality of the nation. The construction of such housing should always take into consideration many aspects in order to create a balanced environment not only based on the suitability of land but also based on the aspects that exist in surrounding. Therefore, this study will be to analyze the priority aspect in process of determining urban residential area using Analytical Hierarchy Process Method. This method aims to determine priority aspect were used based on primary data collection form of questionnaires and interviews to respondents who expert in the field.

Social and Nonsocial Functions of Rostral Prefrontal Cortex: Implications for Education

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Gilbert, Sam J.; Burgess, Paul W.

2008-01-01

In this article, we discuss the role of rostral prefrontal cortex (approximating Brodmann Area 10) in two domains relevant to education: executive function (particularly prospective memory, our ability to realize delayed intentions) and social cognition (particularly our ability to reflect on our own mental states and the mental states of others).…

Plasticity in the Prefrontal Cortex of Adult Rats

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Bryan eKolb

2015-02-01

Full Text Available We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions.

Emotional and Utilitarian Appraisals of Moral Dilemmas Are Encoded in Separate Areas and Integrated in Ventromedial Prefrontal Cortex.

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Hutcherson, Cendri A; Montaser-Kouhsari, Leila; Woodward, James; Rangel, Antonio

2015-09-09

Moral judgment often requires making difficult tradeoffs (e.g., is it appropriate to torture to save the lives of innocents at risk?). Previous research suggests that both emotional appraisals and more deliberative utilitarian appraisals influence such judgments and that these appraisals often conflict. However, it is unclear how these different types of appraisals are represented in the brain, or how they are integrated into an overall moral judgment. We addressed these questions using an fMRI paradigm in which human subjects provide separate emotional and utilitarian appraisals for different potential actions, and then make difficult moral judgments constructed from combinations of these actions. We found that anterior cingulate, insula, and superior temporal gyrus correlated with emotional appraisals, whereas temporoparietal junction and dorsomedial prefrontal cortex correlated with utilitarian appraisals. Overall moral value judgments were represented in an anterior portion of the ventromedial prefrontal cortex. Critically, the pattern of responses and functional interactions between these three sets of regions are consistent with a model in which emotional and utilitarian appraisals are computed independently and in parallel, and passed to the ventromedial prefrontal cortex where they are integrated into an overall moral value judgment. Significance statement: Popular accounts of moral judgment often describe it as a battle for control between two systems, one intuitive and emotional, the other rational and utilitarian, engaged in winner-take-all inhibitory competition. Using a novel fMRI paradigm, we identified distinct neural signatures of emotional and utilitarian appraisals and used them to test different models of how they compete for the control of moral behavior. Importantly, we find little support for competitive inhibition accounts. Instead, moral judgments resembled the architecture of simple economic choices: distinct regions represented emotional

Theta coupling between V4 and prefrontal cortex predicts visual short-term memory performance.

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Liebe, Stefanie; Hoerzer, Gregor M; Logothetis, Nikos K; Rainer, Gregor

2012-01-29

Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3-9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.

Projection from the prefrontal cortex to histaminergic cell groups in the posterior hypothalamic region of the rat. Anterograde tracing with Phaseolus vulgaris leucoagglutinin combined with immunocytochemistry of histidine decarboxylase

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Wouterlood, F.G.; Steinbusch, H.W.M.; Luiten, P.G.M.; Bol, J.G.J.M.

1987-01-01

We investigated the projection from the infralimbic division of the prefrontal cortex (area 25) to histaminergic neurons in the posterior hypothalamic area. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in the prefrontal cortex of rats. Frozen brain sections were subjected to combined

Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia.

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Blasi, Giuseppe; Napolitano, Francesco; Ursini, Gianluca; Di Giorgio, Annabella; Caforio, Grazia; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Attrotto, Maria Teresa; Colagiorgio, Lucia; Todarello, Giovanna; Piva, Francesco; Papazacharias, Apostolos; Masellis, Rita; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Rampino, Antonio; Quarto, Tiziana; Giulietti, Matteo; Lipska, Barbara K; Kleinman, Joel E; Popolizio, Teresa; Weinberger, Daniel R; Usiello, Alessandro; Bertolino, Alessandro

2013-08-01

OBJECTIVE Glycogen synthase kinase 3β (GSK-3β) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3β gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk. METHOD Based on computer predictions, the authors investigated in humans the association of GSK-3β functional variation with 1) GSK-3β mRNA expression from postmortem prefrontal cortex, 2) GSK-3β and β-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia. RESULTS Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3β (rs12630592) was associated with reduced GSK-3β mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3β protein expression and kinase activity, as well as with downstream effects on β-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia. CONCLUSIONS These results suggest that GSK-3β variation is implicated in multiple phenotypes relevant to schizophrenia.

Prefrontal cortex and sensory cortices during working memory: quantity and quality.

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

2015-04-01

The activity in sensory cortices and the prefrontal cortex (PFC) throughout the delay interval of working memory (WM) tasks reflect two aspects of WM-quality and quantity, respectively. The delay activity in sensory cortices is fine-tuned to sensory information and forms the neural basis of the precision of WM storage, while the delay activity in the PFC appears to represent behavioral goals and filters out irrelevant distractions, forming the neural basis of the quantity of task-relevant information in WM. The PFC and sensory cortices interact through different frequency bands of neuronal oscillation (theta, alpha, and gamma) to fulfill goal-directed behaviors.

Unique and shared roles of the posterior parietal and dorsolateral prefrontal cortex in cognitive functions

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Fumi eKatsuki

2012-05-01

Full Text Available The dorsolateral prefrontal and posterior parietal cortex are two parts of a broader brain network involved in the control of cognitive functions such as working memory, spatial attention, and decision making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the dorsolateral prefrontal cortex to influence memory performance, attention allocation and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the dorsolateral prefrontal and posterior parietal cortex, and their underlying mechanisms.

Stimulation in the dorsolateral prefrontal cortex changes subjective evaluation of percepts.

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Tzu-Ching Chiang

Full Text Available Nelson and Narens have proposed a metacognition model that dissociates the objective processing of information (object-level and the subjective evaluation of the performance (i.e., the metalevel. Neurophysiological evidence also indicates that the prefrontal cortices (PFC are the brain areas which perform the metalevel function [1]-[3]. A corresponding neural mechanism of Nelson and Narens's model, called dynamic filtering theory [4], [5], indicates that object-level processing is distributed in the posterior cortices and regulated by the prefrontal cortices with a filtering or gating mechanism to select appropriate signals and suppress inappropriate signals and noise. Based on this model, a hypothesis can be developed that, in the case of uncertainty or overloading of object-level processing, the prefrontal cortices will become more active in order to modulate signals and noise. This hypothesis is supported by a recent fMRI study [6] showing that the PFC (Brodmann area 9, BA9 was activated when subjects were overloaded in a bimodal attentional task, compared to a unimodal task. Here, we report a study showing that applying repetitive transmagnetic stimulation (rTMS over the BA9 in order to interfere with its functional activity resulted in significant increas in guessed responses, compared to three other control conditions (i.e., no-TMS, sham TMS on BA9, and rTMS on Cz. The results are compatible with the dynamic filtering theory and suggest that a malfunction of the PFC would weaken the quality of meta-cognitive percepts and increase the number of guessed responses.

Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity.

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Kenichi Azuma

Full Text Available Multiple chemical sensitivity (MCS is a disorder characterized by nonspecific and recurrent symptoms from various organ systems associated with exposure to low levels of chemicals. Patients with MCS process odors differently than controls do. Previously, we suggested that this odor processing was associated with increased regional cerebral blood flow (rCBF in the prefrontal area during olfactory stimulation using near-infrared spectroscopic (NIRS imaging. The aim of this study was to investigate the association of odor thresholds and changes in rCBF during olfactory stimulation at odor threshold levels in patients with MCS. We investigated changes in the prefrontal area using NIRS imaging and a T&T olfactometer during olfactory stimulation with two different odorants (sweet and fecal at three concentrations (zero, odor recognition threshold, and normal perceived odor level in 10 patients with MCS and six controls. The T&T olfactometer threshold test and subjective assessment of irritating and hedonic odors were also performed. The results indicated that the scores for both unpleasant and pungent odors were significantly higher for those for sweet odors at the normal perceived level in patients with MCS than in controls. The brain responses at the recognition threshold (fecal odor and normal perceived levels (sweet and fecal odors were stronger in patients with MCS than in controls. However, significant differences in the odor detection and recognition thresholds and odor intensity score between the two groups were not observed. These brain responses may involve cognitive and memory processing systems during past exposure to chemicals. Further research regarding the cognitive features of sensory perception and memory due to past exposure to chemicals and their associations with MCS symptoms is needed.

Interaction between the medial prefrontal cortex and hippocampal CA1 area is essential for episodic-like memory in rats.

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Chao, Owen Y; Nikolaus, Susanne; Lira Brandão, Marcus; Huston, Joseph P; de Souza Silva, Maria A

2017-05-01

The interplay between medial prefrontal cortex (mPFC) and hippocampus, particularly the hippocampal CA3 area, is critical for episodic memory. To what extent the mPFC also interacts with the hippocampus CA1 subregion still requires elucidation. To investigate this issue, male rats received unilateral N-methyl- D -aspartate lesions of the mPFC together with unilateral lesions of the hippocampal CA1 area, either in the same (control) or in the opposite hemispheres (disconnection). They underwent an episodic-like memory test, combining what-where-when information, and separate tests for novel object preference (what), object place preference (where) and temporal order memory (when). Compared to controls, the disconnected mPFC-CA1 rats exhibited disrupted episodic-like memory with an impaired integration of the what-where-when elements. Both groups showed intact memories for what and when, while only the control group showed intact memory for where. These findings suggest that the functional interaction of the mPFC-CA1 circuit is crucial for the processing of episodic memory and, in particular, for the integration of the spatial memory component. Copyright © 2017 Elsevier Inc. All rights reserved.

Mirror trends of plasticity and stability indicators in primate prefrontal cortex.

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García-Cabezas, Miguel Á; Joyce, Mary Kate P; John, Yohan J; Zikopoulos, Basilis; Barbas, Helen

2017-10-01

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here, we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity-related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Impaired prefrontal hemodynamic maturation in autism and unaffected siblings.

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Yuki Kawakubo

Full Text Available BACKGROUND: Dysfunctions of the prefrontal cortex have been previously reported in individuals with autism spectrum disorders (ASD. Previous studies reported that first-degree relatives of individuals with ASD show atypical brain activity during tasks associated with social function. However, developmental changes in prefrontal dysfunction in ASD and genetic influences on the phenomena remain unclear. In the present study, we investigated the change in hemoglobin concentration in the prefrontal cortex as measured with near-infrared spectroscopy, in children and adults with ASD during the letter fluency test. Moreover, to clarify the genetic influences on developmental changes in the prefrontal dysfunction in ASD, unaffected siblings of the ASD participants were also assessed. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 27 individuals with high-functioning ASD, age- and IQ-matched 24 healthy non-affected siblings, and 27 unrelated healthy controls aged 5 to 39 years. The relative concentration of hemoglobin ([Hb] in the prefrontal cortex was measured during the letter fluency task. For children, neither the [oxy-Hb] change during the task nor task performances differed significantly among three groups. For adults, the [oxy-Hb] increases during the task were significantly smaller in the bilateral prefrontal cortex in ASD than those in control subjects, although task performances were similar. In the adult siblings the [oxy-Hb] change was intermediate between those in controls and ASDs. CONCLUSION/SIGNIFICANCE: Although indirectly due to a cross-sectional design, the results of this study indicate altered age-related change of prefrontal activity during executive processing in ASD. This is a first near-infrared spectroscopy study that implies alteration in the age-related changes of prefrontal activity in ASD and genetic influences on the phenomena.

Compulsive Sexual Behavior: Prefrontal and Limbic Volume and Interactions

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Schmidt, Casper; Morris, Laurel S.; Kvamme, Timo L.

2017-01-01

prefrontal cortex (whole brain, cluster corrected FWE P motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions...

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

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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.

Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults

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Ayaka Ishii-Takahashi

2014-01-01

Full Text Available The differential diagnosis of autism spectrum disorders (ASDs and attention deficit hyperactivity disorder (ADHD based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.

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

Schizophrenia; from structure to function with special focus on the mediodorsal thalamic prefrontal loop

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Pakkenberg, B.; Scheel-Kruger, J.; Kristiansen, L.V.

2009-01-01

studies in postmortem brain from patients with schizophrenia have reported divergent and often opposing findings in the total number of neurons and volume of the mediodorsal (MD) thalamic nucleus, and to a lesser degree in its reciprocally associated areas of the prefrontal cortex. Similarly, quantitative...

Contribution of different regions of the prefrontal cortex and lesion laterality to deficit of decision-making on the Iowa Gambling Task.

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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.

Prefrontal glucose deficits in murderers lacking psychosocial deprivation.

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Raine, A; Phil, D; Stoddard, J; Bihrle, S; Buchsbaum, M

1998-01-01

Previous research has suggested that links between autonomic nervous system functioning and violence are strongest in those who come from benign home backgrounds, but there appears to be no similar research using brain-imaging measures of central nervous system functioning. It was hypothesized that murderers who had no early psychosocial deprivation (e.g., no childhood abuse, family neglect) would demonstrate lower prefrontal glucose metabolism than murderers with early psychosocial deprivation and a group of normal controls. Murderers from a previous study, which showed prefrontal deficits in murderers, were assessed for psychosocial deprivation and divided into those with and without deprivation. Murderers without any clear psychosocial deficits were significantly lower on prefrontal glucose metabolism than murderers with psychosocial deficits and controls. These results suggest that murderers lacking psychosocial deficits are characterized by prefrontal deficits. It is argued that among violent offenders without deprived home backgrounds, the "social push" to violence is minimized, and consequently, brain abnormalities provide a relatively stronger predisposition to violence in this group.

Selective reductions in prefrontal glucose metabolism in murderers.

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Raine, A; Buchsbaum, M S; Stanley, J; Lottenberg, S; Abel, L; Stoddard, J

1994-09-15

This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

Stress amplifies sex differences in primate prefrontal profiles of gene expression.

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Lee, Alex G; Hagenauer, Megan; Absher, Devin; Morrison, Kathleen E; Bale, Tracy L; Myers, Richard M; Watson, Stanley J; Akil, Huda; Schatzberg, Alan F; Lyons, David M

2017-11-02

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults. Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys. Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex. Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.

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Annabella Di Giorgio

Full Text Available BACKGROUND: Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560 and in the nicotinic receptor α5 gene (CHRNA5, rs16969968 on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. METHODS: A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T and CHNRA5 rs16969968 (G>A on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. RESULTS: We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. CONCLUSIONS: The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.

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Di Giorgio, Annabella; Smith, Ryan M; Fazio, Leonardo; D'Ambrosio, Enrico; Gelao, Barbara; Tomasicchio, Aldo; Selvaggi, Pierluigi; Taurisano, Paolo; Quarto, Tiziana; Masellis, Rita; Rampino, Antonio; Caforio, Grazia; Popolizio, Teresa; Blasi, Giuseppe; Sadee, Wolfgang; Bertolino, Alessandro

2014-01-01

Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.

Where vision meets memory: prefrontal-posterior networks for visual object constancy during categorization and recognition.

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Schendan, Haline E; Stern, Chantal E

2008-07-01

Objects seen from unusual relative to more canonical views require more time to categorize and recognize, and, according to object model verification theories, additionally recruit prefrontal processes for cognitive control that interact with parietal processes for mental rotation. To test this using functional magnetic resonance imaging, people categorized and recognized known objects from unusual and canonical views. Canonical views activated some components of a default network more on categorization than recognition. Activation to unusual views showed that both ventral and dorsal visual pathways, and prefrontal cortex, have key roles in visual object constancy. Unusual views activated object-sensitive and mental rotation (and not saccade) regions in ventrocaudal intraparietal, transverse occipital, and inferotemporal sulci, and ventral premotor cortex for verification processes of model testing on any task. A collateral-lingual sulci "place" area activated for mental rotation, working memory, and unusual views on correct recognition and categorization trials to accomplish detailed spatial matching. Ventrolateral prefrontal cortex and object-sensitive lateral occipital sulcus activated for mental rotation and unusual views on categorization more than recognition, supporting verification processes of model prediction. This visual knowledge framework integrates vision and memory theories to explain how distinct prefrontal-posterior networks enable meaningful interactions with objects in diverse situations.

Prefrontal cerebral blood volume patterns while playing video games--a near-infrared spectroscopy study.

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Nagamitsu, Shinichiro; Nagano, Miki; Yamashita, Yushiro; Takashima, Sachio; Matsuishi, Toyojiro

2006-06-01

Video game playing is an attractive form of entertainment among school-age children. Although this activity reportedly has many adverse effects on child development, these effects remain controversial. To investigate the effect of video game playing on regional cerebral blood volume, we measured cerebral hemoglobin concentrations using near-infrared spectroscopy in 12 normal volunteers consisting of six children and six adults. A Hitachi Optical Topography system was used to measure hemoglobin changes. For all subjects, the video game Donkey Kong was played on a Game Boy device. After spectroscopic probes were positioned on the scalp near the target brain regions, the participants were asked to play the game for nine periods of 15s each, with 15-s rest intervals between these task periods. Significant increases in bilateral prefrontal total-hemoglobin concentrations were observed in four of the adults during video game playing. On the other hand, significant decreases in bilateral prefrontal total-hemoglobin concentrations were seen in two of the children. A significant positive correlation between mean oxy-hemoglobin changes in the prefrontal region and those in the bilateral motor cortex area was seen in adults. Playing video games gave rise to dynamic changes in cerebral blood volume in both age groups, while the difference in the prefrontal oxygenation patterns suggested an age-dependent utilization of different neural circuits during video game tasks.

The Development of the Ventral Prefrontal Cortex and Social Flexibility

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Nelson, Eric E.; Guyer, Amanda E.

2011-01-01

Over the last several years a number of studies in both humans and animals have suggested that the orbitofrontal and ventrolateral prefrontal cortices play an important role in generating flexible behavior. We suggest that input from these brain regions contribute to three functions involved in generating flexible behavior within social contexts: valuation, inhibition, and rule use. Recent studies have also demonstrated that the prefrontal cortex undergoes a prolonged course of maturation that extends well after puberty. Here, we review evidence that the prolonged development of these prefrontal regions parallels a slowly emerging ability for flexible social behavior. We also speculate on the possibility that sensitive periods for organizing social behavior may be embedded within this developmental time-fame. Finally, we discuss the role of prefrontal cortex in adolescent mood and anxiety disorders, particularly as orbitofrontal and ventrolateral prefrontal cortices are engaged in a social context. PMID:21804907

Study the left prefrontal cortex activity of Chinese children with dyslexia in phonological processing by NIRS

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Zhang, Zhili; Li, Ting; Zheng, Yi; Luo, Qingming; Song, Ranran; Gong, Hui

2006-02-01

Developmental dyslexia, a kind of prevalent psychological disease, represents that dyslexic children have unexpected difficulties in phonological processing and recognition test of Chinese characters. Some functional imaging technologies, such as fMRI and PET, have been used to study the brain activities of the children with dyslexia whose first language is English. In this paper, a portable, 16-channel, continuous-wave (CW) NIRS instrument was used to monitor the concentration changes of each hemoglobin species when Chinese children did the task of phonological processing and recognition test. The NIRS recorded the hemodynamic changes in the left prefrontal cortex of the children. 20 dyslexia-reading children (10~12 years old) and 20 normal-reading children took part in the phonological processing of Chinese characters including the phonological awareness section and the phonological decoding section. During the phonological awareness section, the changed concentration of deoxy-hemoglobin in dyslexia-reading children were significantly higher (p<0.05) than normal-reading children in the left ventrolateral prefrontal cortex (VLPFC). While in the phonological decoding section, both normal and dyslexic reading children had more activity in the left VLPFC, but only normal-reading children had activity in the left middorsal prefrontal cortex. In conclusion, both dyslexic and normal-reading children have activity in the left prefrontal cortex, but the degree and the areas of the prefrontal cortex activity are different between them when they did phonological processing.

Neuron density is decreased in the prefrontal cortex in Williams syndrome.

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Lew, Caroline Horton; Brown, Chelsea; Bellugi, Ursula; Semendeferi, Katerina

2017-01-01

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. Autism Res 2017, 10: 99-112. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Developmental trajectories of abuse--an hypothesis for the effects of early childhood maltreatment on dorsolateral prefrontal cortical development.

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Burrus, Caley

2013-11-01

The United States has a high rate of child maltreatment, with nearly 12 in 1000 children being victims of abuse or neglect. Child abuse strongly predicts negative life outcomes, especially in areas of emotional and mental health. Abused children are also more likely than their peers to engage in violence and enter the juvenile justice system, as well as to become abusive parents themselves. Research has shown that child abuse and trauma can lead to decreased hippocampal volume, which could be indicative of abnormal hippocampal development. Hippocampal development appears to directly affect the development of the dorsolateral prefrontal cortex, a brain area responsible for emotion regulation, cognitive reappraisal, and general executive function. Therefore, I hypothesize that if child abuse results in abnormal hippocampal development, which leads to abnormal dorsolateral prefrontal cortex development, many of the correlated risk factors of child abuse, such as emotionally-laden parenting and unfavorable cognitive distortions regarding children's behaviors, may be in part caused by underdevelopment or abnormal functioning of the dorsolateral prefrontal cortex, as a function of the individual's own experiences with abuse during childhood. If this hypothesis is supported with future research, more targeted, successful, and cost-effective prevention and treatment protocols could ensue. For instance, programs that have been empirically shown to increase the activity of the dorsolateral prefrontal cortex, such as cognitive behavioral therapy, could be effective in decreasing the incidence of intergenerational transfer of abuse. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Model of Amygdala-Hippocampal-Prefrontal Interaction in Fear Conditioning and Extinction in Animals

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Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard J.; Myers, Catherine E.

2013-01-01

Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus…

Functional connection between posterior superior temporal gyrus and ventrolateral prefrontal cortex in human.

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Garell, P C; Bakken, H; Greenlee, J D W; Volkov, I; Reale, R A; Oya, H; Kawasaki, H; Howard, M A; Brugge, J F

2013-10-01

The connection between auditory fields of the temporal lobe and prefrontal cortex has been well characterized in nonhuman primates. Little is known of temporofrontal connectivity in humans, however, due largely to the fact that invasive experimental approaches used so successfully to trace anatomical pathways in laboratory animals cannot be used in humans. Instead, we used a functional tract-tracing method in 12 neurosurgical patients with multicontact electrode arrays chronically implanted over the left (n = 7) or right (n = 5) perisylvian temporal auditory cortex (area PLST) and the ventrolateral prefrontal cortex (VLPFC) of the inferior frontal gyrus (IFG) for diagnosis and treatment of medically intractable epilepsy. Area PLST was identified by the distribution of average auditory-evoked potentials obtained in response to simple and complex sounds. The same sounds evoked little if there is any activity in VLPFC. A single bipolar electrical pulse (0.2 ms, charge-balanced) applied between contacts within physiologically identified PLST resulted in polyphasic evoked potentials clustered in VLPFC, with greatest activation being in pars triangularis of the IFG. The average peak latency of the earliest negative deflection of the evoked potential on VLPFC was 13.48 ms (range: 9.0-18.5 ms), providing evidence for a rapidly conducting pathway between area PLST and VLPFC.

Functional organization and visual representations in human ventral lateral prefrontal cortex

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Annie Wai Yiu Chan

2013-07-01

Full Text Available Recent neuroimaging studies in both human and non-human primates have identified face selective activation in the ventral lateral prefrontal cortex even in the absence of working memory demands. Further, research has suggested that this face-selective response is largely driven by the presence of the eyes. However, the nature and origin of visual category responses in the ventral lateral prefrontal cortex remain unclear. Further, in a broader sense, how do these findings relate to our current understandings of lateral prefrontal cortex? What do these findings tell us about the underlying function and organization principles of the ventral lateral prefrontal cortex? What is the future direction for investigating visual representations in this cortex? This review focuses on the function, topography, and circuitry of the ventral lateral prefrontal cortex to enhance our understanding of the evolution and development of this cortex.

Prefrontal cortex activation during obstacle negotiation: What's the effect size and timing?

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Maidan, Inbal; Shustak, Shiran; Sharon, Topaz; Bernad-Elazari, Hagar; Geffen, Nimrod; Giladi, Nir; Hausdorff, Jeffrey M; Mirelman, Anat

2018-04-01

Obstacle negotiation is a daily activity that requires the integration of sensorimotor and cognitive information. Recent studies provide evidence for the important role of prefrontal cortex during obstacle negotiation. We aimed to explore the effects of obstacle height and available response time on prefrontal activation. Twenty healthy young adults (age: 30.1 ± 1.0 years; 50% women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles at heights of 50 mm and 100 mm. Prefrontal activation was measured using a functional near-infrared spectroscopy system. Kinect cameras measured the obstacle negotiation strategy. Prefrontal activation was defined based on mean level of HbO 2 before, during and after obstacle negotiation and the HbO 2 slope from gait initiation and throughout the task. Changes between types of obstacles were assessed using linear-mix models and partial correlation analyses evaluated the relationship between prefrontal activation and the distance between the feet as the subjects traversed the obstacles. Different obstacle heights showed similar changes in prefrontal activation measures (p > 0.210). However, during unanticipated obstacles, the slope of the HbO 2 response was steeper (p = 0.048), as compared to anticipated obstacles. These changes in prefrontal activation during negotiation of unanticipated obstacles were correlated with greater distance of the leading foot after the obstacles (r = 0.831, p = 0.041). These findings are the first to show that the pattern of prefrontal activation depends on the nature of the obstacle. More specifically, during unanticipated obstacles the recruitment of the prefrontal cortex is faster and greater than during negotiating anticipated obstacles. These results provide evidence of the important role of the prefrontal cortex and the ability of healthy young adults to tailor the activation pattern to different types of obstacles. Copyright © 2018

Dorsolateral Prefrontal Cortex Drives Mesolimbic Dopaminergic Regions to Initiate Motivated Behavior

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Ballard, Ian C.; Murty, Vishnu P.; Carter, R. McKell; MacInnes, Jeffrey J.; Huettel, Scott A.; Adcock, R. Alison

2011-01-01

How does the brain translate information signaling potential rewards into motivation to get them? Motivation to obtain reward is thought to depend on the midbrain, (particularly the ventral tegmental area, VTA), the nucleus accumbens (NAcc), and the dorsolateral prefrontal cortex (dlPFC), but it is not clear how the interactions amongst these regions relate to reward-motivated behavior. To study the influence of motivation on these reward-responsive regions and on their interactions, we used ...

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

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Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (pright inferior occipital gyrus (pbrain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (pbrain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cathodal Transcranial Direct Current Stimulation Over Left Dorsolateral Prefrontal Cortex Area Promotes Implicit Motor Learning in a Golf Putting Task.

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Zhu, Frank F; Yeung, Andrew Y; Poolton, Jamie M; Lee, Tatia M C; Leung, Gilberto K K; Masters, Rich S W

2015-01-01

Implicit motor learning is characterized by low dependence on working memory and stable performance despite stress, fatigue, or multi-tasking. However, current paradigms for implicit motor learning are based on behavioral interventions that are often task-specific and limited when applied in practice. To investigate whether cathodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) area during motor learning suppressed working memory activity and reduced explicit verbal-analytical involvement in movement control, thereby promoting implicit motor learning. Twenty-seven healthy individuals practiced a golf putting task during a Training Phase while receiving either real cathodal tDCS stimulation over the left DLPFC area or sham stimulation. Their performance was assessed during a Test phase on another day. Verbal working memory capacity was assessed before and after the Training Phase, and before the Test Phase. Compared to sham stimulation, real stimulation suppressed verbal working memory activity after the Training Phase, but enhanced golf putting performance during the Training Phase and the Test Phase, especially when participants were required to multi-task. Cathodal tDCS over the left DLPFC may foster implicit motor learning and performance in complex real-life motor tasks that occur during sports, surgery or motor rehabilitation. Copyright © 2015 Elsevier Inc. All rights reserved.

Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice.

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Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Sreedhar, Remya; Afrin, Rejina; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nomoto, Mayumi; Sone, Hirohito; Suzuki, Kenji; Watanabe, Kenichi

2014-09-05

BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Nonlinear responses within the medial prefrontal cortex reveal when specific implicit information influences economic decision making.

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Deppe, Michael; Schwindt, Wolfram; Kugel, Harald; Plassmann, Hilke; Kenning, Peter

2005-04-01

The authors used functional magnetic resonance imaging (fMRI) to investigate how individual economic decisions are influenced by implicit memory contributions. Twenty-two participants were asked to make binary decisions between different brands of sensorily nearly undistinguishable consumer goods. Changes of brain activity comparing decisions in the presence or absence of a specific target brand were detected by fMRI. Only when the tar get brand was the participant's favorite one did the authors find reduced activation in the dorsolateral prefrontal, posterior parietal, and occipital cortices and the left premotor area (Brodmann areas [BA] 9, 46, 7/19, and 6). Simultaneously, activity was increased in the inferior precuneus and posterior cingulate (BA 7), right superior frontal gyrus (BA 10), right supramarginal gyrus (BA 40), and, most pronounced, in the ventromedial prefrontal cortex (BA 10). For products mainly distinguishable by brand information, the authors revealed a nonlinear winner-take-all effect for a participant's favorite brand characterized, on one hand, by reduced activation in brain areas associated with working memory and reasoning and, on the other hand, increased activation in areas involved in processing of emotions and self-reflections during decision making.

White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

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Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

2012-01-16

Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Interactive effects of music and prefrontal cortex stimulation in modulating response inhibition.

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Mansouri, Farshad Alizadeh; Acevedo, Nicola; Illipparampil, Rosin; Fehring, Daniel J; Fitzgerald, Paul B; Jaberzadeh, Shapour

2017-12-22

Influential hypotheses propose that alterations in emotional state influence decision processes and executive control of behavior. Both music and transcranial direct current stimulation (tDCS) of prefrontal cortex affect emotional state, however interactive effects of music and tDCS on executive functions remain unknown. Learning to inhibit inappropriate responses is an important aspect of executive control which is guided by assessing the decision outcomes such as errors. We found that high-tempo music, but not low-tempo music or low-level noise, significantly influenced learning and implementation of inhibitory control. In addition, a brief period of tDCS over prefrontal cortex specifically interacted with high-tempo music and altered its effects on executive functions. Measuring event-related autonomic and arousal response of participants indicated that exposure to task demands and practice led to a decline in arousal response to the decision outcome and high-tempo music enhanced such practice-related processes. However, tDCS specifically moderated the high-tempo music effect on the arousal response to errors and concomitantly restored learning and improvement in executive functions. Here, we show that tDCS and music interactively influence the learning and implementation of inhibitory control. Our findings indicate that alterations in the arousal-emotional response to the decision outcome might underlie these interactive effects.

Predicting risk-taking behavior from prefrontal resting-state activity and personality.

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Bettina Studer

Full Text Available Risk-taking is subject to considerable individual differences. In the current study, we tested whether resting-state activity in the prefrontal cortex and trait sensitivity to reward and punishment can help predict risk-taking behavior. Prefrontal activity at rest was assessed in seventy healthy volunteers using electroencephalography, and compared to their choice behavior on an economic risk-taking task. The Behavioral Inhibition System/Behavioral Activation System scale was used to measure participants' trait sensitivity to reward and punishment. Our results confirmed both prefrontal resting-state activity and personality traits as sources of individual differences in risk-taking behavior. Right-left asymmetry in prefrontal activity and scores on the Behavioral Inhibition System scale, reflecting trait sensitivity to punishment, were correlated with the level of risk-taking on the task. We further discovered that scores on the Behavioral Inhibition System scale modulated the relationship between asymmetry in prefrontal resting-state activity and risk-taking. The results of this study demonstrate that heterogeneity in risk-taking behavior can be traced back to differences in the basic physiology of decision-makers' brains, and suggest that baseline prefrontal activity and personality traits might interplay in guiding risk-taking behavior.

Predicting Risk-Taking Behavior from Prefrontal Resting-State Activity and Personality

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Studer, Bettina; Pedroni, Andreas; Rieskamp, Jörg

2013-01-01

Risk-taking is subject to considerable individual differences. In the current study, we tested whether resting-state activity in the prefrontal cortex and trait sensitivity to reward and punishment can help predict risk-taking behavior. Prefrontal activity at rest was assessed in seventy healthy volunteers using electroencephalography, and compared to their choice behavior on an economic risk-taking task. The Behavioral Inhibition System/Behavioral Activation System scale was used to measure participants’ trait sensitivity to reward and punishment. Our results confirmed both prefrontal resting-state activity and personality traits as sources of individual differences in risk-taking behavior. Right-left asymmetry in prefrontal activity and scores on the Behavioral Inhibition System scale, reflecting trait sensitivity to punishment, were correlated with the level of risk-taking on the task. We further discovered that scores on the Behavioral Inhibition System scale modulated the relationship between asymmetry in prefrontal resting-state activity and risk-taking. The results of this study demonstrate that heterogeneity in risk-taking behavior can be traced back to differences in the basic physiology of decision-makers’ brains, and suggest that baseline prefrontal activity and personality traits might interplay in guiding risk-taking behavior. PMID:24116176

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

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Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Macià, Dídac; Pera, Vanessa; Hernández-Ribas, Rosa; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2015-11-01

Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with

Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model.

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Hara, Yuta; Takuma, Kazuhiro; Takano, Erika; Katashiba, Keisuke; Taruta, Atsuki; Higashino, Kosuke; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

2015-08-01

Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way. Copyright © 2015 Elsevier B.V. All rights reserved.

Decreased prefrontal cortical dopamine transmission in alcoholism.

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Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

2014-08-01

Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

I find you more attractive … after (prefrontal cortex) stimulation

NARCIS (Netherlands)

Ferrari, C.; Lega, C.; Tamietto, M.; Nadal, M.; Cattaneo, Z.

2015-01-01

Facial attractiveness seems to be perceived immediately. Neuroimaging evidence suggests that the appraisal of facial attractiveness is mediated by a network of cortical and subcortical regions, mainly encompassing the reward circuit, but also including prefrontal cortices. The prefrontal cortex is

MINING LAKES OF THE AGHIREŞ AREA: GENESIS, EVOLUTION AND MORPHOMETRIC ASPECTS

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V. MĂCICĂŞAN

2012-03-01

Full Text Available Mining lakes of the Aghireş area: Genesis, evolution and morphometric aspects. Mining activities are heavily influencing and destroying the landscape worldwide. In Aghireş mining perimeter, exploitation workings have led to extreme and irreversible environmental damages, especially regarding the geomorphologic and hydrological situation. After cessation of underground mining and initiation of quarry exploitation, certain mining galleries collapsed and were afterwards flooded by precipitation and re-ascending groundwater, leading to the formation of lacustrine units. Later, the abandoned quarries have undergone the same flooding process. In this paper, we report on the genesis, evolution and the current characteristics of these bodies of water, referred to as mining lakes. In addition, using the GIS technology, the morphometry of the mining lakes is presented in this paper. Due to their predominant current use, as for recreational purposes, the sustainable management of the mining lakes is an important ecological and socio-economical factor for the Aghireş area. For the majority of mining lakes, restoration measures may be necessary due to the demands of the European legislation as well as to the demands of a specific socio-economic use in the future (e.g. bathing lakes or fishing lakes. These aspects of investigation will constitute a prerequisite for effective environmental management and rehabilitation strategies.

Activation of the Prefrontal Cortex While Performing a Task at Preferred Slow Pace and Metronome Slow Pace: A Functional Near-Infrared Spectroscopy Study

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Kaori Shimoda

2014-01-01

Full Text Available Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10 was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions.

Activation of the prefrontal cortex while performing a task at preferred slow pace and metronome slow pace: a functional near-infrared spectroscopy study.

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Shimoda, Kaori; Moriguchi, Yoshiya; Tsuchiya, Kenji; Katsuyama, Shiori; Tozato, Fusae

2014-01-01

Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions.

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

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Cwik, Jan C; Sartory, Gudrun; Nuyken, Malte; Schürholt, Benjamin; Seitz, Rüdiger J

2017-09-01

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

Reduced prefrontal connectivity in psychopathy.

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Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

2011-11-30

Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task.

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Kopf, Juliane; Schecklmann, Martin; Hahn, Tim; Dresler, Thomas; Dieler, Alica C; Herrmann, Martin J; Fallgatter, Andreas J; Reif, Andreas

2011-08-15

Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Prefrontal contributions to visual selective attention.

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Squire, Ryan F; Noudoost, Behrad; Schafer, Robert J; Moore, Tirin

2013-07-08

The faculty of attention endows us with the capacity to process important sensory information selectively while disregarding information that is potentially distracting. Much of our understanding of the neural circuitry underlying this fundamental cognitive function comes from neurophysiological studies within the visual modality. Past evidence suggests that a principal function of the prefrontal cortex (PFC) is selective attention and that this function involves the modulation of sensory signals within posterior cortices. In this review, we discuss recent progress in identifying the specific prefrontal circuits controlling visual attention and its neural correlates within the primate visual system. In addition, we examine the persisting challenge of precisely defining how behavior should be affected when attentional function is lost.

Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

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Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

2013-03-01

Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

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Bick, Sarah K B; Folley, Bradley S; Mayer, Jutta S; Park, Sohee; Charles, P David; Camalier, Corrie R; Pallavaram, Srivatsan; Konrad, Peter E; Neimat, Joseph S

2017-04-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction. © 2016 International Neuromodulation Society.

Cyto-, myelo- and chemoarchitecture of the prefrontal cortex of the Cebus monkey

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2011-01-01

Background According to several lines of evidence, the great expansion observed in the primate prefrontal cortex (PfC) was accompanied by the emergence of new cortical areas during phylogenetic development. As a consequence, the structural heterogeneity noted in this region of the primate frontal lobe has been associated with diverse behavioral and cognitive functions described in human and non-human primates. A substantial part of this evidence was obtained using Old World monkeys as experimental model; while the PfC of New World monkeys has been poorly studied. In this study, the architecture of the PfC in five capuchin monkeys (Cebus apella) was analyzed based on four different architectonic tools, Nissl and myelin staining, histochemistry using the lectin Wisteria floribunda agglutinin and immunohistochemistry using SMI-32 antibody. Results Twenty-two architectonic areas in the Cebus PfC were distinguished: areas 8v, 8d, 9d, 12l, 45, 46v, 46d, 46vr and 46dr in the lateral PfC; areas 11l, 11m, 12o, 13l, 13m, 13i, 14r and 14c in the orbitofrontal cortex, with areas 14r and 14c occupying the ventromedial corner; areas 32r, 32c, 25 and 9m in the medial PfC, and area 10 in the frontal pole. This number is significantly higher than the four cytoarchitectonic areas previously recognized in the same species. However, the number and distribution of these areas in Cebus were to a large extent similar to those described in Old World monkeys PfC in more recent studies. Conclusions The present parcellation of the Cebus PfC considerably modifies the scheme initially proposed for this species but is in line with previous studies on Old World monkeys. Thus, it was observed that the remarkable anatomical similarity between the brains of genera Macaca and Cebus may extend to architectonic aspects. Since monkeys of both genera evolved independently over a long period of time facing different environmental pressures, the similarities in the architectonic maps of PfC in both genera

Sex differences in prefrontal hemodynamic response to mental arithmetic as assessed by near-infrared spectroscopy.

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Yang, Hongyu; Wang, Ying; Zhou, Zhenyu; Gong, Hui; Luo, Qingming; Wang, Yiwen; Lu, Zuhong

2009-12-01

Sex differences in cognitive tasks have been widely investigated. With brain-imaging techniques, the functions of the brain during the performance of tasks can be examined. Mental arithmetic and near-infrared spectroscopy (NIRS) were used to assess sex differences in prefrontal area activation in a functional brain study. Healthy college students were recruited to perform 2 mental arithmetic tasks. In the first (easy) task, students had to subtract a 1-digit number from a 3-digit number. In the second (difficult) task, they had to subtract a 2-digit number from a 3-digit number. Changes in the concentration of oxygenated hemoglobin (oxy-Hgb) in the prefrontal area during the tasks were measured with NIRS. Thirty students (15 men, 15 women; mean [SD] age: 24.9 [2.2] and 24.3 [2.6] years, respectively) were recruited from Southeast University, Nanjing, China, to participate in the study. The concentration of oxy-Hgb increased during both mental arithmetic tasks (difficult task vs easy task, mean [SD] % arbitrary units: 4.36 [4.38] vs 2.26 [2.82]; F(1,28) = 222.80; P men and women were observed in the mean (SD) response time (men vs women, sec: 3.60 [0.74] vs 3.56 [0.49] for the easy task, 6.55 [0.77] vs 6.44 [0.75] for the difficult task; F(1,28) = 0.67; P = NS) or accuracy rate (men vs women, %: 95.33 [7.40] vs 92.77 [8.80] for the easy task, 62.67 [28.56] vs 54.67 [18.75] for the difficult task; F(1,28) = 0.54; P = NS). Male students showed neural efficiency (less prefrontal activation in subjects with better performance) during the difficult task. In these subjects, sex differences in prefrontal response when performing mental arithmetic were associated with the intensity of the task. Compared with men, women had greater efficiency in task performance (ie, less activation or oxygen consumption for equal performance). Copyright 2009 Excerpta Medica Inc. All rights reserved.

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 ...

High social desirability and prefrontal cortical activity in cancer patients: a preliminary study.

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Tashiro, Manabu; Juengling, Freimut D; Moser, Ernst; Reinhardt, Michael J; Kubota, Kazuo; Yanai, Kazuhiko; Sasaki, Hidetada; Nitzsche, Egbert U; Kumano, Hiroaki; Itoh, Masatoshi

2003-04-01

Social desirability is sometimes associated with poor prognosis in cancer patients. Psycho-neuro-immune interaction has been hypothesized as an underlying mechanism of the negative clinical outcome. Purpose of this study was to examine possible effects of high social desirability on the regional brain activity in patients with malignant diseases. Brain metabolism of 16 patients with various malignant diseases was measured by PET with 18F-fluorodeoxyglucose (FDG). Patients were divided into 2 groups using median split on Marlowe & Crown's Social Desirability Scale (MC), controlling for age, gender, and for severity of depression and anxiety, the possible two major influential factors. A group comparison of the regional cerebral activity was calculated on a voxel-by-voxel basis using statistical parametric mapping (SPM). The subgroup comparison showed that the high social desirability was associated with relatively increased metabolism in the cortical regions in the prefrontal, temporal and occipital lobes as well as in the anterior cingulate gyrus. High social desirability seems to be associated with increased activity in the prefrontal and other cortical areas. The finding is in an accordance with previous studies that demonstrated an association between prefrontal damage and anti-social behavior. Functional neuroimaging seems to be useful not only for psychiatric evaluation of major factors such as depression and anxiety but also for further psychosocial factors in cancer patients.

Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

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Massimiliano Conson

Full Text Available Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS over dorsolateral prefrontal cortex (DLPFC. To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task, and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

Association between prefrontal N-acetylaspartate and insight in psychotic disorders.

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Larabi, Daouia I; Liemburg, Edith J; Pijnenborg, Gerdina H M; Sibeijn-Kuiper, Anita; de Vos, Annerieke E; Bais, Leonie; Knegtering, Henderikus; Ćurčić-Blake, Branislava; Aleman, André

2017-01-01

Insight is impaired in most patients with psychosis and has been associated with poorer prognosis. The exact neural basis of impaired insight is still unknown, but it may involve disrupted prefrontal neural connectivity. Numerous studies have indeed found white matter (WM) abnormalities in psychosis. The association between prefrontal WM abnormalities and insight has not been studied yet by means of proton magnetic resonance spectroscopy ( 1 H-MRS). 1 H-MRS can be used to measure N-acetylaspartate (NAA), which is considered to be a marker of neuronal integrity. We measured insight with the Birchwood Insight Scale (BIS) as well as item G12 of the Positive and Negative Syndrome Scale (PANSS) in 88 patients with psychosis. Prefrontal WM concentrations of NAA and ratios of NAA to creatine (Cr) were assessed with 1 H-MRS. Nonparametric partial correlational analyses were conducted between NAA concentrations and insight controlling for illness duration, standardized antipsychotic dose, symptom scores, voxel grey matter content and voxel cerebrospinal fluid content. We found a significant correlation between reduced NAA/Cr ratios and poorer insight as measured with the BIS, which remained significant after additional correction for full width at half maximum, signal/noise and age. This is the first study reporting a relationship between lower prefrontal concentrations of a marker of neuronal integrity and impaired insight, providing further evidence that prefrontal pathology may play an important role in impaired insight in psychosis. This may be explained by the involvement of the prefrontal cortex in several executive and metacognitive functions, such as cognitive flexibility and perspective taking. Copyright © 2016 Elsevier B.V. All rights reserved.

Power spectrum scale invariance identifies prefrontal dysregulation in paranoid schizophrenia.

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Radulescu, Anca R; Rubin, Denis; Strey, Helmut H; Mujica-Parodi, Lilianne R

2012-07-01

Theory and experimental evidence suggest that complex living systems function close to the boundary of chaos, with erroneous organization to an improper dynamical range (too stiff or chaotic) underlying system-wide dysregulation and disease. We hypothesized that erroneous organization might therefore also characterize paranoid schizophrenia, via optimization abnormalities in the prefrontal-limbic circuit regulating emotion. To test this, we acquired fMRI scans from 35 subjects (N = 9 patients with paranoid schizophrenia and N = 26 healthy controls), while they viewed affect-valent stimuli. To quantify dynamic regulation, we analyzed the power spectrum scale invariance (PSSI) of fMRI time-courses and computed the geometry of time-delay (Poincaré) maps, a measure of variability. Patients and controls showed distinct PSSI in two clusters (k(1) : Z = 4.3215, P = 0.00002 and k(2) : Z = 3.9441, P = 0.00008), localized to the orbitofrontal/medial prefrontal cortex (Brodmann Area 10), represented by β close to white noise in patients (β ≈ 0) and in the pink noise range in controls (β ≈ -1). Interpreting the meaning of PSSI differences, the Poincaré maps indicated less variability in patients than controls (Z = -1.9437, P = 0.05 for k(1) ; Z = -2.5099, P = 0.01 for k(2) ). That the dynamics identified Brodmann Area 10 is consistent with previous schizophrenia research, which implicates this area in deficits of working memory, executive functioning, emotional regulation and underlying biological abnormalities in synaptic (glutamatergic) transmission. Our results additionally cohere with a large body of work finding pink noise to be the normal range of central function at the synaptic, cellular, and small network levels, and suggest that patients show less supple responsivity of this region. Copyright © 2011 Wiley-Liss, Inc.

View-Independent Working Memory Representations of Artificial Shapes in Prefrontal and Posterior Regions of the Human Brain.

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Christophel, Thomas B; Allefeld, Carsten; Endisch, Christian; Haynes, John-Dylan

2017-05-13

Traditional views of visual working memory postulate that memorized contents are stored in dorsolateral prefrontal cortex using an adaptive and flexible code. In contrast, recent studies proposed that contents are maintained by posterior brain areas using codes akin to perceptual representations. An important question is whether this reflects a difference in the level of abstraction between posterior and prefrontal representations. Here, we investigated whether neural representations of visual working memory contents are view-independent, as indicated by rotation-invariance. Using functional magnetic resonance imaging and multivariate pattern analyses, we show that when subjects memorize complex shapes, both posterior and frontal brain regions maintain the memorized contents using a rotation-invariant code. Importantly, we found the representations in frontal cortex to be localized to the frontal eye fields rather than dorsolateral prefrontal cortices. Thus, our results give evidence for the view-independent storage of complex shapes in distributed representations across posterior and frontal brain regions. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Right prefrontal TMS disrupts interregional anticipatory EEG alpha activity during shifting of visuospatial attention

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Paul eSauseng

2011-10-01

Full Text Available Visual attention can be shifted in space without moving the eyes. Amplitude decrease of rhythmical brain activity around 10 Hz (so called alpha activity at contralateral posterior sites has been reported during covert shifts of visuospatial attention to one visual hemifield. Alpha amplitude increase, on the other hand, can be found at ipsilateral visual cortex. There is some evidence suggesting an involvement of prefrontal brain areas during the control of attention-related anticipatory alpha amplitude asymmetry. However, the exact neural mechanism by which prefrontal cortex influences visual processing has not been completely clear yet. This open question has been studied in detail using a multimodal approach combining transcranial magnetic stimulation (TMS and multichannel electroencephalography (EEG in healthy humans. Slow (1 Hz repetitive TMS inducing an inhibitory effect at the stimulation site was delivered either to right frontal eye field or a control site (vertex. Subsequently, participants had to perform a spatial cueing task in which covert shifts of attention were required to either the left or the right visual hemi-field. After stimulation at the vertex (control condition a pattern of anticipatory, attention-related ipsilateral alpha increase / contralateral alpha decrease over posterior recording sites could be obtained. Additionally, there was pronounced coupling between (in particular right FEF and posterior brain sites. When, however, the right prefrontal cortex had been virtually lesioned preceding the task, these EEG correlates of visuospatial attention were attenuated. Notably, the effect of TMS at the right FEF on interregional fronto-parietal alpha coupling predicted the effect on response times. This suggests that visual attention processes associated with posterior EEG alpha activity are at least partly top-down controlled by the prefrontal cortex.

Schizophrenia: a tale of two critical periods for prefrontal cortical development

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Selemon, L D; Zecevic, N

2015-01-01

Schizophrenia is a disease of abnormal brain development. Considerable evidence now indicates that environmental factors have a causative role in schizophrenia. Elevated incidence of the disease has been linked to a wide range of disturbances in the prenatal environment and to social factors and drug intake during adolescence. Here we examine neurodevelopment of the prefrontal cortex in the first trimester of gestation and during adolescence to gain further insight into the neurodevelopmental processes that may be vulnerable in schizophrenia. Early embryonic development of the prefrontal cortex is characterized by cell proliferation, including renewal of progenitor cells, generation of early transient cell populations and neurogenesis of subcortical populations. Animal models show that curtailing early gestational cell proliferation produces schizophrenia-like pathology in the prefrontal cortex and mimics key behavioral and cognitive symptoms of the disease. At the other end of the spectrum, elimination of excitatory synapses is the fundamental process occurring during adolescent maturation in the prefrontal cortex. Adverse social situations that elevate stress increase dopamine stimulation of the mesocortical pathway and may lead to exaggerated synaptic pruning during adolescence. In a non-human primate model, dopamine hyperstimulation has been shown to decrease prefrontal pyramidal cell spine density and to be associated with profound cognitive dysfunction. Development of the prefrontal cortex in its earliest stage in gestation and in its final stage in adolescence represents two critical periods of vulnerability for schizophrenia in which cell proliferation and synaptic elimination, respectively, may be influenced by environmental factors. PMID:26285133

Prefrontal cortex activity during swallowing in dysphagia patients.

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Lee, Jun; Yamate, Chisato; Taira, Masato; Shinoda, Masamichi; Urata, Kentaro; Maruno, Mitsuru; Ito, Reio; Saito, Hiroto; Gionhaku, Nobuhito; Iinuma, Toshimitsu; Iwata, Koichi

2018-05-24

Prefrontal cortex activity is modulated by flavor and taste stimuli and changes during swallowing. We hypothesized that changes in the modulation of prefrontal cortex activity by flavor and taste were associated with swallowing movement and evaluated brain activity during swallowing in patients with dysphagia. To evaluate prefrontal cortex activity in dysphagia patients during swallowing, change in oxidized hemoglobin (z-score) was measured with near-infrared spectroscopy while dysphagia patients and healthy controls swallowed sweetened/unsweetened and flavored/unflavored jelly. Total z-scores were positive during swallowing of flavored/unsweetened jelly and negative during swallowing of unflavored/sweetened jelly in controls but negative during swallowing of sweetened/unsweetened and flavored/unflavored jelly in dysphagia patients. These findings suggest that taste and flavor during food swallowing are associated with positive and negative z-scores, respectively. Change in negative and positive z-scores may be useful in evaluating brain activity of dysphagia patients during swallowing of sweetened and unsweetened food.

Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study.

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Dlabac-de Lange, Jozarni J; Liemburg, Edith J; Bais, Leonie; van de Poel-Mustafayeva, Aida T; de Lange-de Klerk, Elly S M; Knegtering, Henderikus; Aleman, André

Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with 1 H-Magnetic Resonance Spectroscopy ( 1 H-MRS). Patients were randomized to a 3-week course of active or sham high-frequency rTMS. Pre-treatment and post-treatment 1 H-MRS data were available for 24 patients with schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Absolute metabolite concentrations were calculated using LCModel with the water peak as reference. To explore the association between treatment condition and changes in concentration of Glx and NAA, we applied a linear regression model. We observed an increase of Glx concentration in the active treatment group and a decrease of Glx concentration in the group receiving sham treatment. The association between changes in Glx concentration and treatment condition was significant. No significant associations between changes in NAA and treatment condition were found. Noninvasive neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx concentration in the prefrontal cortex of patients with schizophrenia. Larger studies are needed to confirm these findings and further elucidate the underlying neural working mechanism of rTMS. Copyright © 2016 Elsevier Inc. All rights reserved.

Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.

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Chafee, Matthew V; Crowe, David A

2017-10-11

In this issue, Loonis et al. (2017) provide the first description of unique synchrony patterns differentiating implicit and explicit forms of learning in monkey prefrontal networks. Their results have broad implications for how prefrontal networks integrate the two learning mechanisms to control behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Functions of delay-period activity in the prefrontal cortex and mnemonic scotomas revisited

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Shintaro eFunahashi

2015-02-01

Full Text Available Working memory is one of key concepts to understand functions of the prefrontal cortex. Delay-period activity is an important neural correlate to understand the role of working memory in prefrontal functions. The importance of delay-period activity is that this activity can encode not only visuospatial information but also a variety of information including non-spatial visual features, auditory and tactile stimuli, task rules, expected reward, and numerical quantity. This activity also participates in a variety of information processing including sensory-to-motor information transformation. These mnemonic features of delay-period activity enable to perform various important operations that the prefrontal cortex participates in, such as executive controls, and therefore, support the notion that working memory is an important function to understand prefrontal functions. On the other hand, although experiments using manual versions of the delayed-response task had revealed many important findings, an oculomotor version of this task enabled us to use multiple cue positions, exclude postural orientation during the delay period, and further prove the importance of mnemonic functions of the prefrontal cortex. In addition, monkeys with unilateral lesions exhibited specific impairment only in the performance of memory-guided saccades directed toward visual cues in the visual field contralateral to the lesioned hemisphere. This result indicates that memories for visuospatial coordinates in each hemifield are processed primarily in the contralateral prefrontal cortex. This result further strengthened the idea of mnemonic functions of the prefrontal cortex. Thus, the mnemonic functions of the prefrontal cortex and delay-period activity may not need to be reconsidered, but should be emphasized.

Medial prefrontal cortex subserves diverse forms of self-reflection.

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Jenkins, Adrianna C; Mitchell, Jason P

2011-01-01

The ability to think about oneself--to self--reflect--is one of the defining features of the human mind. Recent research has suggested that this ability may be subserved by a particular brain region: the medial prefrontal cortex (MPFC). However, although humans can contemplate a variety of different aspects of themselves, including their stable personality traits, current feelings, and physical attributes, no research has directly examined the extent to which these different forms of self-reflection are subserved by common mechanisms. To address this question, participants were scanned using functional magnetic resonance imaging (fMRI) while making judgments about their own personality traits, current mental states, and physical attributes as well as those of another person. Whereas some brain regions responded preferentially during only one form of self-reflection, a robust region of MPFC was engaged preferentially during self-reflection across all three types of judgment. These results suggest that--although dissociable--diverse forms of self-referential thought draw on a shared cognitive process subserved by MPFC.

Effects of prefrontal rTMS on autonomic reactions to affective pictures.

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Berger, Christoph; Domes, Gregor; Balschat, Johannes; Thome, Johannes; Höppner, Jacqueline

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) can modulate the excitability of stimulated cortical areas, such as prefrontal areas involved in emotion regulation. Low frequency (LF) rTMS is expected to have inhibitory effects on prefrontal regions, and thereby should disinhibit limbic activity, resulting in enhanced emotional and autonomic reactions. For high frequency (HF) rTMS, the opposite pattern might be assumed. The objective of this study was to determine the effects of different rTMS frequencies applied to the right dlPFC on autonomic functions and on emotional perception. In a crossover design, two groups of 20 healthy young women were either stimulated with one session of LF rTMS (1 Hz) or one session of HF rTMS (10 Hz), compared to sham stimulation. We assessed phasic cardiac responses (PCR), skin conductance reactions (SCR), and emotional appraisal of emotional pictures as well as recognition memory after each rTMS application. After LF rTMS, PCR (heart rate deceleration) during presentation of pictures with negative and neutral valence was significantly increased compared to the presentation of positive pictures. In contrast, the modulatory effect of picture valence and arousal on the cardiac orienting response was absent after HF rTMS. Our results suggest that frontal LF rTMS indirectly activates the ANS via inhibition of the right dlPFC activity, likely by enhancing the sensory processing or attention to aversive and neutral stimuli.

Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

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Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

2015-06-30

Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study.

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Byun, Kyeongho; Hyodo, Kazuki; Suwabe, Kazuya; Ochi, Genta; Sakairi, Yosuke; Kato, Morimasa; Dan, Ippeita; Soya, Hideaki

2014-09-01

Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions. Copyright © 2014 Elsevier Inc. All rights reserved.

Compulsive Sexual Behavior: Prefrontal and Limbic Volume and Interactions

DEFF Research Database (Denmark)

Schmidt, Casper; Morris, Laurel S.; Kvamme, Timo L.

2017-01-01

with matched healthy volunteers (HV). Methods: Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were...... prefrontal cortex (whole brain, cluster corrected FWE P motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions...

Ritmos circadianos y neurotransmisores : estudios en la corteza prefrontal de la rata

OpenAIRE

Márquez de Prado García, Blanca

2004-01-01

El objetivo de esta tesis doctoral fue el estudio los posibles ritmos circadianos de los neurotransmisores glutamato, GABA, dopamina y acetilcolina en la corteza prefrontal. Una vez descritos los ritmos circadianos de estos neurotransmisores en corteza prefrontal se estudió su regulación por cambios en el fotoperíodo y la melatonina. Se estudiaron también los efectos del envejecimiento sobre los ritmos circadianos neurotransmisores en corteza prefrontal, estriado y núcleo accumbens. Se realiz...

Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

Science.gov (United States)

Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

2011-03-01

Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

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Gregory R Rompala

Full Text Available Pharmacological and genetic studies support a role for NMDA receptor (NMDAR hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1 deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice, in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior. Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes.

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Rompala, Gregory R; Zsiros, Veronika; Zhang, Shuqin; Kolata, Stefan M; Nakazawa, Kazu

2013-01-01

Pharmacological and genetic studies support a role for NMDA receptor (NMDAR) hypofunction in the etiology of schizophrenia. We have previously demonstrated that NMDAR obligatory subunit 1 (GluN1) deletion in corticolimbic interneurons during early postnatal development is sufficient to confer schizophrenia-like phenotypes in mice. However, the consequence of NMDAR hypofunction in cortical excitatory neurons is not well delineated. Here, we characterize a conditional knockout mouse strain (CtxGluN1 KO mice), in which postnatal GluN1 deletion is largely confined to the excitatory neurons in layer II/III of the medial prefrontal cortex and sensory cortices, as evidenced by the lack of GluN1 mRNA expression in in situ hybridization immunocytochemistry as well as the lack of NMDA currents with in vitro recordings. Mutants were impaired in prepulse inhibition of the auditory startle reflex as well as object-based short-term memory. However, they did not exhibit impairments in additional hallmarks of schizophrenia-like phenotypes (e.g. spatial working memory, social behavior, saccharine preference, novelty and amphetamine-induced hyperlocomotion, and anxiety-related behavior). Furthermore, upon administration of the NMDA receptor antagonist, MK-801, there were no differences in locomotor activity versus controls. The mutant mice also showed negligible levels of reactive oxygen species production following chronic social isolation, and recording of miniature-EPSC/IPSCs from layer II/III excitatory neurons in medial prefrontal cortex suggested no alteration in GABAergic activity. All together, the mutant mice displayed cognitive deficits in the absence of additional behavioral or cellular phenotypes reflecting schizophrenia pathophysiology. Thus, NMDAR hypofunction in prefrontal and cortical excitatory neurons may recapitulate only a cognitive aspect of human schizophrenia symptoms.

Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia.

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Blasi, Giuseppe; Popolizio, Teresa; Taurisano, Paolo; Caforio, Grazia; Romano, Raffaella; Di Giorgio, Annabella; Sambataro, Fabio; Rubino, Valeria; Latorre, Valeria; Lo Bianco, Luciana; Fazio, Leonardo; Nardini, Marcello; Weinberger, Daniel R; Bertolino, Alessandro

2009-07-15

Earlier imaging studies in schizophrenia have reported abnormal amygdala and prefrontal cortex activity during emotion processing. We investigated with functional magnetic resonance imaging (fMRI) during emotion processing changes in activity of the amygdala and of prefrontal cortex in patients with schizophrenia during 8 weeks of olanzapine treatment. Twelve previously drug-free/naive patients with schizophrenia were treated with olanzapine for 8 weeks and underwent two fMRI scans after 4 and 8 weeks of treatment during implicit and explicit emotional processing. Twelve healthy subjects were also scanned twice to control for potential repetition effects. Results showed a diagnosis by time interaction in left amygdala and a diagnosis by time by task interaction in right ventrolateral prefrontal cortex. In particular, activity in left amygdala was greater in patients than in controls at the first scan during both explicit and implicit processing, while it was lower in patients at the second relative to the first scan. Furthermore, during implicit processing, right ventrolateral prefrontal cortex activity was lower in patients than controls at the first scan, while it was greater in patients at the second relative to the first scan. These results suggest that longitudinal treatment with olanzapine may be associated with specific changes in activity of the amygdala and prefrontal cortex during emotional processing in schizophrenia.

Specific properties of the SI and SII somatosensory areas and their effects on motor control: a system neurophysiological study.

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Friedrich, Julia; Mückschel, Moritz; Beste, Christian

2018-03-01

Sensorimotor integration is essential for successful motor control and the somatosensory modality has been shown to have strong effects on the execution of motor plans. The primary (SI) and the secondary somatosensory (SII) cortices are known to differ in their neuroanatomical connections to prefrontal areas, as well as in their involvement to encode cognitive aspects of tactile processing. Here, we ask whether the area-specific processing architecture or the structural neuroanatomical connections with prefrontal areas determine the efficacy of sensorimotor integration processes for motor control. In a system neurophysiological study including EEG signal decomposition (i.e., residue iteration decomposition, RIDE) and source localization, we investigated this question using vibrotactile stimuli optimized for SI or SII processing. The behavioral data show that when being triggered via the SI area, inhibitory control of motor processes is stronger as when being triggered via the SII area. On a neurophysiological level, these effects were reflected in the C-cluster as a result of a temporal decomposition of EEG data, indicating that the sensory processes affecting motor inhibition modulate the response selection level. These modulations were associated with a stronger activation of the right inferior frontal gyrus extending to the right middle frontal gyrus as parts of a network known to be involved in inhibitory motor control when response inhibition is triggered over SI. In addition, areas important for sensorimotor integration like the postcentral gyrus and superior parietal cortex showed activation differences. The data suggest that connection patterns are more important for sensorimotor integration and control than the more restricted area-specific processing architecture.

Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

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Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2005-07-01

Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25{+-}2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% {+-} 1.3% and 10.6% {+-} 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% {+-} 4.5% vs. 6.6% {+-} 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release.

Dopamine release in human striatum induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex

International Nuclear Information System (INIS)

Cho, Sang Soo; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

2005-01-01

Animal study suggests that prefrontal cortex plays an important Animal studies suggest that prefrontal cortex plays an important role in the modulation of dopamine (DA) release in subcortical areas. However, little is known about the relationship between DA release and prefrontal activation in human. We investigated whether repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (DLPFC) influences DA release in human striatum with SPECT measurements of striatal binding of [123I)iodobenzamide (IBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy male volunteers (age, 25±2 yr) were studied with brain [123I]IBZM SPECT under three conditions (resting, Sham stimulation, and active rTMS over left DLPFC), while receiving a bolus plus constant infusion of [123I]IBZM DLPFC was defined as a 6 cm anterior and 1cm lateral from the primary motor cortex. rTMS session consisted of three blocks, in each block, 15 trains of 2 see duration were delivered with 10 Hz stimulation frequency, 100% motor threshold, and between-train intervals of 10 sec. Striatal V3', calculated as (striatal - occipital) / occipital activity ratio, was measured under equilibrium condition, at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over DLPFC induced reduction of V3' in the ipsilateral and contralateral striatum by 9.7% ± 1.3% and 10.6% ± 3.2%, respectively, compared with sham procedures (P < 0.01 and P < 0.01, respectively), indicating striatal DA release elicited by rTMS over DLPFC. V3' reduction in the ipsilateral caudate nucleus was greater than that in the contralateral caudate nucleus (9.9% ± 4.5% vs. 6.6% ± 3.1%, P < 0.05). These data demonstrate DA release in human striatum induced by rTMS over DLPFC, supporting that cortico-striatal fibers originating in prefrontal cortex are involved in local DA release

Hyperresponsivity and impaired prefrontal control of the mesolimbic reward system in schizophrenia.

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Richter, Anja; Petrovic, Aleksandra; Diekhof, Esther K; Trost, Sarah; Wolter, Sarah; Gruber, Oliver

2015-12-01

Schizophrenia is characterized by substantial dysfunctions of reward processing, leading to detrimental consequences for decision-making. The neurotransmitter dopamine is responsible for the transmission of reward signals and also known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), sixteen medicated patients with schizophrenia and sixteen healthy controls performed the 'desire-reason dilemma' (DRD) paradigm. This paradigm allowed us to directly investigate reward-related brain activations depending on the interaction of bottom-up and top-down mechanisms, when a previously conditioned reward stimulus had to be rejected to achieve a superordinate long-term goal. Both patients and controls showed significant activations in the mesolimbic reward system. In patients with schizophrenia, however, we found a significant hyperactivation of the left ventral striatum (vStr) when they were allowed to accept the conditioned reward stimuli, and a reduced top-down regulation of activation in the ventral striatum (vStr) and ventral tegmental area (VTA) while having to reject the immediate reward to pursue the superordinate task-goal. Moreover, while healthy subjects exhibited a negative functional coupling of the vStr with both the anteroventral prefrontal cortex (avPFC) and the ventromedial prefrontal cortex (VMPFC) in the dilemma situation, this functional coupling was significantly impaired in the patient group. These findings provide evidence for an increased ventral striatal activation to reward stimuli and an impaired top-down control of reward signals by prefrontal brain regions in schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.

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Wei, Luqing; Chen, Hong; Wu, Guo-Rong

2018-01-01

The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.

The neural dynamics of competition resolution for language production in the prefrontal cortex.

Science.gov (United States)

Bourguignon, Nicolas J; Ohashi, Hiroki; Nguyen, Don; Gracco, Vincent L

2018-03-01

Previous research suggests a pivotal role of the prefrontal cortex (PFC) in word selection during tasks of confrontation naming (CN) and verb generation (VG), both of which feature varying degrees of competition between candidate responses. However, discrepancies in prefrontal activity have also been reported between the two tasks, in particular more widespread and intense activation in VG extending into (left) ventrolateral PFC, the functional significance of which remains unclear. We propose that these variations reflect differences in competition resolution processes tied to distinct underlying lexico-semantic operations: Although CN involves selecting lexical entries out of limited sets of alternatives, VG requires exploration of possible semantic relations not readily evident from the object itself, requiring prefrontal areas previously shown to be recruited in top-down retrieval of information from lexico-semantic memory. We tested this hypothesis through combined independent component analysis of functional imaging data and information-theoretic measurements of variations in selection competition associated with participants' performance in overt CN and VG tasks. Selection competition during CN engaged the anterior insula and surrounding opercular tissue, while competition during VG recruited additional activity of left ventrolateral PFC. These patterns remained after controlling for participants' speech onset latencies indicative of possible task differences in mental effort. These findings have implications for understanding the neural-computational dynamics of cognitive control in language production and how it relates to the functional architecture of adaptive behavior. © 2017 Wiley Periodicals, Inc.

Hippocampal-prefrontal connectivity predicts midfrontal oscillations and long-term memory performance

NARCIS (Netherlands)

Cohen, M.X.

2011-01-01

The hippocampus and prefrontal cortex interact to support working memory (WM) and long-term memory [1, 2 and 3]. Neurophysiologically, WM is thought to be subserved by reverberatory activity of distributed networks within the prefrontal cortex (PFC) [2, 4, 5, 6, 7 and 8], which become synchronized

Neurons responsive to face-view in the primate ventrolateral prefrontal cortex.

Science.gov (United States)

Romanski, L M; Diehl, M M

2011-08-25

Studies have indicated that temporal and prefrontal brain regions process face and vocal information. Face-selective and vocalization-responsive neurons have been demonstrated in the ventrolateral prefrontal cortex (VLPFC) and some prefrontal cells preferentially respond to combinations of face and corresponding vocalizations. These studies suggest VLPFC in nonhuman primates may play a role in communication that is similar to the role of inferior frontal regions in human language processing. If VLPFC is involved in communication, information about a speaker's face including identity, face-view, gaze, and emotional expression might be encoded by prefrontal neurons. In the following study, we examined the effect of face-view in ventrolateral prefrontal neurons by testing cells with auditory, visual, and a set of human and monkey faces rotated through 0°, 30°, 60°, 90°, and -30°. Prefrontal neurons responded selectively to either the identity of the face presented (human or monkey) or to the specific view of the face/head, or to both identity and face-view. Neurons which were affected by the identity of the face most often showed an increase in firing in the second part of the stimulus period. Neurons that were selective for face-view typically preferred forward face-view stimuli (0° and 30° rotation). The neurons which were selective for forward face-view were also auditory responsive compared to other neurons which responded to other views or were unselective which were not auditory responsive. Our analysis showed that the human forward face (0°) was decoded better and also contained the most information relative to other face-views. Our findings confirm a role for VLPFC in the processing and integration of face and vocalization information and add to the growing body of evidence that the primate ventrolateral prefrontal cortex plays a prominent role in social communication and is an important model in understanding the cellular mechanisms of communication

Prefrontal system dysfunction and credit card debt.

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Spinella, Marcello; Yang, Bijou; Lester, David

2004-10-01

Credit card use often involves a disadvantageous allocation of finances because they allow for spending beyond means and buying on impulse. Accordingly they are associated with increased bankruptcy, anxiety, stress, and health problems. Mounting evidence from functional neuroimaging and clinical studies implicates prefrontal-subcortical systems in processing financial information. This study examined the relationship of credit card debt and executive functions using the Frontal System Behavior Scale (FRSBE). After removing the influences of demographic variables (age, sex, education, and income), credit card debt was associated with the Executive Dysfunction scale, but not the Apathy or Disinhibition scales. This suggests that processes of conceptualizing and organizing finances are most relevant to credit card debt, and implicates dorsolateral prefrontal dysfunction.

Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation.

Science.gov (United States)

Duque, Julie; Labruna, Ludovica; Verset, Sophie; Olivier, Etienne; Ivry, Richard B

2012-01-18

Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated in a timely manner. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution, whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation.

Dissociating the role of prefrontal and premotor cortices in controlling inhibitory mechanisms during motor preparation

Science.gov (United States)

Duque, Julie; Labruna, Ludovica; Verset, Sophie; Olivier, Etienne; Ivry, Richard B.

2012-01-01

Top-down control processes are critical to select goal-directed actions in flexible environments. In humans, these processes include two inhibitory mechanisms that operate during response selection: one is involved in solving a competition between different response options, the other ensures that a selected response is initiated timely. Here, we evaluated the role of dorsal premotor cortex (PMd) and lateral prefrontal cortex (LPF) of healthy subjects in these two forms of inhibition by using an innovative transcranial magnetic stimulation (TMS) protocol combining repetitive TMS (rTMS) over PMd or LPF and a single pulse TMS (sTMS) over primary motor cortex (M1). sTMS over M1 allowed us to assess inhibitory changes in corticospinal excitability, while rTMS was used to produce transient disruption of PMd or LPF. We found that rTMS over LPF reduces inhibition associated with competition resolution whereas rTMS over PMd decreases inhibition associated with response impulse control. These results emphasize the dissociable contributions of these two frontal regions to inhibitory control during motor preparation. The association of LPF with competition resolution is consistent with the role of this area in relatively abstract aspects of control related to goal maintenance, ensuring that the appropriate response is selected in a variable context. In contrast, the association of PMd with impulse control is consistent with the role of this area in more specific processes related to motor preparation and initiation. PMID:22262879

Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

Science.gov (United States)

Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J

2010-11-01

Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis

Differential roles of the infralimbic and prelimbic areas of the prefrontal cortex in reconsolidation of a traumatic memory.

Science.gov (United States)

Levin, Natali; Kritman, Milly; Maroun, Mouna; Akirav, Irit

2017-09-01

Studies about reconsolidation of conditioned fear memories have shown that pharmacological manipulation at memory reactivation can attenuate or enhance the subsequent expression of the conditioned fear response. Here we examined the effects of a single injection of the mTOR inhibitor rapamycin (Rap) into the infralimbic (IL) and prelimbic (PL) areas [which compose the ventromedial prefrontal cortex (PFC)] on reconsolidation and extinction of a traumatic fear memory. We found opposite effects of Rap infused into the PL and IL on reconsolidation and extinction: intra-PL Rap and systemic Rap impaired reconsolidation and facilitated extinction whereas intra-IL Rap enhanced reconsolidation and impaired extinction. These effects persisted at least 10 days after reactivation. Shock exposure induced anxiety-like behavior and impaired working memory and intra-IL and -PL Rap normalized these effects. Finally, when measured after fear retrieval, shocked rats exhibited reduced and increased phosphorylated p70s6K levels in the IL and basolateral amygdala, respectively. No effect on phosphorylated p70s6K levels was observed in the PL. The study points to the differential roles of the IL and PL in memory reconsolidation and extinction. Moreover, inhibiting mTOR via rapamycin following reactivation of a fear memory may be a novel approach in attenuating enhanced fear memories. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations.

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Ortega, Leonardo A; Glueck, Amanda C; Uhelski, Megan; Fuchs, Perry N; Papini, Mauricio R

2013-05-01

The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cortex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following continuous vs. partial reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity. Lesions of the VLO reduced suppression of consummatory behavior after the incentive downshift, but only during the first downshift trial, and also eliminated the enhancement of anticipatory behavior during partial reinforcement, relative to continuous reinforcement, in autoshaping. There was no evidence of specific effects of mPFC lesions on incentive downshifts. Open-field activity was also reduced by VLO lesions, but only in the central area, whereas mPFC lesions had no observable effects on activity. Animals with mPFC lesions exhibited decreased consumption of the lowest sucrose concentration, whereas no effects were observed in animals with VLO lesions. These results suggest that the VLO may exert nonassociative (i.e., motivational, emotional) influences on behavior in situations involving incentive downshifts. No clear role on incentive downshift was revealed by mPFC lesions. Copyright © 2013 Elsevier B.V. All rights reserved.

Lateral Orbitofrontal Cortical Modulation on the Medial Prefrontal Cortex-Amygdala Pathway: Differential Regulation of Intra-Amygdala GABAA and GABAB Receptors.

Science.gov (United States)

Chang, Chun-Hui

2017-07-01

The basolateral complex of the amygdala receives inputs from neocortical areas, including the medial prefrontal cortex and lateral orbitofrontal cortex. Earlier studies have shown that lateral orbitofrontal cortex activation exerts an inhibitory gating on medial prefrontal cortex-amygdala information flow. Here we examined the individual role of GABAA and GABAB receptors in this process. In vivo extracellular single-unit recordings were done in anesthetized rats. We searched amygdala neurons that fire in response to medial prefrontal cortex activation, tested lateral orbitofrontal cortex gating at different delays (lateral orbitofrontal cortex-medial prefrontal cortex delays: 25, 50, 100, 250, 500, and 1000 milliseconds), and examined differential contribution of GABAA and GABAB receptors with iontophoresis. Relative to baseline, lateral orbitofrontal cortex stimulation exerted an inhibitory modulatory gating on the medial prefrontal cortex-amygdala pathway and was effective up to a long delay of 500 ms (long-delay latencies at 100, 250, and 500 milliseconds). Moreover, blockade of intra-amygdala GABAA receptors with bicuculline abolished the lateral orbitofrontal cortex inhibitory gating at both short- (25 milliseconds) and long-delay (100 milliseconds) intervals, while blockade of GABAB receptors with saclofen reversed the inhibitory gating at long delay (100 milliseconds) only. Among the majority of the neurons examined (8 of 9), inactivation of either GABAA or GABAB receptors during baseline did not change evoked probability per se, suggesting that local feed-forward inhibitory mechanism is pathway specific. Our results suggest that the effect of lateral orbitofrontal cortex inhibitory modulatory gating was effective up to 500 milliseconds and that intra-amygdala GABAA and GABAB receptors differentially modulate the short- and long-delay lateral orbitofrontal cortex inhibitory gating on the medial prefrontal cortex-amygdala pathway. © The Author 2017

[Brodmann Areas 39 and 40: Human Parietal Association Area and Higher Cortical Function].

Science.gov (United States)

Sakurai, Yasuhisa

2017-04-01

The anatomy and function of the angular gyrus (Brodmann Area 39) and supramarginal gyrus (Brodmann Area 40) are described here. Both gyri constitute the inferior part of the parietal lobe. Association fibers from the angular gyrus project to the dorsolateral prefrontal cortex via the superior longitudinal fasciculus (SLF) II/arcuate fasciculus (AF), whereas those from the supramarginal gyrus project to the ventrolateral prefrontal cortex via SLF III/AF. Damage to the left angular gyrus causes kanji agraphia (lexical agraphia) and mild anomia, whereas damage to the left supramarginal gyrus causes kana alexia (phonological dyslexia) and kana agraphia (phonological agraphia). Damage to either gyrus causes Gerstmann's syndrome (finger agnosia, left-right disorientation, agraphia and acalculia) and verbal short-term memory impairment. "Angular alexia with agraphia" results from damage to the middle occipital gyrus posterior to the angular gyrus. Alexia and agraphia, with lesions in the angular or supramarginal gyrus, are characterized by kana transposition errors in reading words, which suggests the impairment of sequential phonological processing.

Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making.

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van 't Wout, Mascha; Kahn, René S; Sanfey, Alan G; Aleman, André

2005-11-07

Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task. This is restricted to correlational evidence, however, and it remains unclear whether the dorsolateral prefrontal cortex is crucial for strategic decision-making. The present study used repetitive transcranial magnetic stimulation in order to investigate the causal role of the dorsolateral prefrontal cortex in strategic decision-making in the Ultimatum Game. The results showed that repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex resulted in an altered decision-making strategy compared with sham stimulation. We conclude that the dorsolateral prefrontal cortex is causally implicated in strategic decision-making in healthy human study participants.

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

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Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

1998-01-01

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Prefrontal cortex glutamate correlates with mental perspective-taking.

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Christiane Montag

Full Text Available BACKGROUND: Dysfunctions in theory of mind and empathic abilities have been suggested as core symptoms in major psychiatric disorders including schizophrenia and autism. Since self monitoring, perspective taking and empathy have been linked to prefrontal (PFC and anterior cingulate cortex (ACC function, neurotransmitter variations in these areas may account for normal and pathological variations of these functions. Converging evidence indicates an essential role of glutamatergic neurotransmission in psychiatric diseases with pronounced deficits in empathy. However, the role of the glutamate system for different dimensions of empathy has not been investigated so far. METHODOLOGY/PRINCIPAL FINDINGS: Absolute concentrations of cerebral glutamate in the ACC, left dorsolateral PFC and left hippocampus were determined by 3-tesla proton magnetic resonance spectroscopy (1H-MRS in 17 healthy individuals. Three dimensions of empathy were estimated by a self-rating questionnaire, the Interpersonal Reactivity Index (IRI. Linear regression analysis showed that dorsolateral PFC glutamate concentration was predicted by IRI factor "perspective taking" (T = -2.710, p = 0.018; adjusted alpha-level of 0.017, Bonferroni but not by "empathic concern" or "personal distress". No significant relationship between IRI subscores and the glutamate levels in the ACC or left hippocampus was detected. CONCLUSIONS/SIGNIFICANCE: This is the first study to investigate the role of the glutamate system for dimensions of theory of mind and empathy. Results are in line with recent concepts that executive top-down control of behavior is mediated by prefrontal glutamatergic projections. This is a preliminary finding that needs a replication in an independent sample.

Right prefrontal rTMS treatment for refractory auditory command hallucinations - a neuroSPECT assisted case study.

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Schreiber, Shaul; Dannon, Pinhas N; Goshen, Elinor; Amiaz, Revital; Zwas, Tzila S; Grunhaus, Leon

2002-11-30

Auditory command hallucinations probably arise from the patient's failure to monitor his/her own 'inner speech', which is connected to activation of speech perception areas of the left cerebral cortex and to various degrees of dysfunction of cortical circuits involved in schizophrenia as supported by functional brain imaging. We hypothesized that rapid transcranial magnetic stimulation (rTMS), by increasing cortical activation of the right prefrontal brain region, would bring about a reduction of the hallucinations. We report our first schizophrenic patient affected with refractory command hallucinations treated with 10 Hz rTMS. Treatment was performed over the right dorsolateral prefrontal cortex, with 1200 magnetic stimulations administered daily for 20 days at 90% motor threshold. Regional cerebral blood flow changes were monitored with neuroSPECT. Clinical evaluation and scores on the Positive and Negative Symptoms Scale and the Brief Psychiatric Rating Scale demonstrated a global improvement in the patient's condition, with no change in the intensity and frequency of the hallucinations. NeuroSPECT performed at intervals during and after treatment indicated a general improvement in cerebral perfusion. We conclude that right prefrontal rTMS may induce a general clinical improvement of schizophrenic brain function, without directly influencing the mechanism involved in auditory command hallucinations.

Transitions between Multiband Oscillatory Patterns Characterize Memory-Guided Perceptual Decisions in Prefrontal Circuits.

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Wimmer, Klaus; Ramon, Marc; Pasternak, Tatiana; Compte, Albert

2016-01-13

between sensory and cognitive processing. Here, we studied rhythmic electrical activity in the monkey prefrontal cortex, an area implicated in working memory, decision making, and executive control. Monkeys had to identify and remember a visual motion pattern and compare it to a second pattern. We found orderly transitions between rhythmic activity where the same frequency channels were active in all ongoing prefrontal computations. This supports prefrontal circuit dynamics that transitions rapidly between complex rhythmic patterns during structured cognitive tasks. Copyright © 2016 the authors 0270-6474/16/360489-17$15.00/0.

An integrative theory of prefrontal cortex function.

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Miller, E K; Cohen, J D

2001-01-01

The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

Changes in prefrontal-limbic function in major depression after 15 months of long-term psychotherapy.

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Anna Buchheim

Full Text Available Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV unmedicated outpatients (N = 16 and control participants matched for sex, age, and education (N = 17 before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

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Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F.; Bruns, Georg; Taubner, Svenja

2012-01-01

Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy. PMID:22470470

Thinning of the lateral prefrontal cortex during adolescence predicts emotion regulation in females.

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Vijayakumar, Nandita; Whittle, Sarah; Yücel, Murat; Dennison, Meg; Simmons, Julian; Allen, Nicholas B

2014-11-01

Adolescence is a crucial period for the development of adaptive emotion regulation strategies. Despite the fact that structural maturation of the prefrontal cortex during adolescence is often assumed to underlie the maturation of emotion regulation strategies, no longitudinal studies have directly assessed this relationship. This study examined whether use of cognitive reappraisal strategies during late adolescence was predicted by (i) absolute prefrontal cortical thickness during early adolescence and (ii) structural maturation of the prefrontal cortex between early and mid-adolescence. Ninety-two adolescents underwent baseline and follow-up magnetic resonance imaging scans when they were aged approximately 12 and 16 years, respectively. FreeSurfer software was used to obtain cortical thickness estimates for three prefrontal regions [anterior cingulate cortex; dorsolateral prefrontal cortex (dlPFC); ventrolateral prefrontal cortex (vlPFC)]. The Emotion Regulation Questionnaire was completed when adolescents were aged approximately 19 years. Results showed that greater cortical thinning of the left dlPFC and left vlPFC during adolescence was significantly associated with greater use of cognitive reappraisal in females, though no such relationship was evident in males. Furthermore, baseline left dlPFC thickness predicted cognitive reappraisal at trend level. These findings suggest that cortical maturation may play a role in the development of adaptive emotion regulation strategies during adolescence. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Distraction decreases prefrontal oxygenation: A NIRS study.

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Ozawa, Sachiyo; Hiraki, Kazuo

2017-04-01

When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

Prefrontal Cortex and Social Cognition in Mouse and Man

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Bicks, Lucy K.; Koike, Hiroyuki; Akbarian, Schahram; Morishita, Hirofumi

2015-01-01

Social cognition is a complex process that requires the integration of a wide variety of behaviors, including salience, reward-seeking, motivation, knowledge of self and others, and flexibly adjusting behavior in social groups. Not surprisingly, social cognition represents a sensitive domain commonly disrupted in the pathology of a variety of psychiatric disorders including Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ). Here, we discuss convergent research from animal models to human disease that implicates the prefrontal cortex (PFC) as a key regulator in social cognition, suggesting that disruptions in prefrontal microcircuitry play an essential role in the pathophysiology of psychiatric disorders with shared social deficits. We take a translational perspective of social cognition, and review three key behaviors that are essential to normal social processing in rodents and humans, including social motivation, social recognition, and dominance hierarchy. A shared prefrontal circuitry may underlie these behaviors. Social cognition deficits in animal models of neurodevelopmental disorders like ASD and SCZ have been linked to an altered balance of excitation and inhibition (E/I ratio) within the cortex generally, and PFC specifically. A clear picture of the mechanisms by which altered E/I ratio in the PFC might lead to disruptions of social cognition across a variety of behaviors is not well understood. Future studies should explore how disrupted developmental trajectory of prefrontal microcircuitry could lead to altered E/I balance and subsequent deficits in the social domain. PMID:26635701

Prefrontal Cortex Cognitive Deficits in Children Treated Early and Continuously for PKU.

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Diamond, Adele; Prevor, Meredith B.; Druin, Donald P.; Callender, Glenda

1997-01-01

Hypothesized that elevated ratio of phenylalanine to tyrosine in blood of children with phenylketonuria uniquely affects cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in tyrosine. Found that children whose phenylalanine levels were three to five…

Alterations in visual cortical activation and connectivity with prefrontal cortex during working memory updating in major depressive disorder.

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Le, Thang M; Borghi, John A; Kujawa, Autumn J; Klein, Daniel N; Leung, Hoi-Chung

2017-01-01

The present study examined the impacts of major depressive disorder (MDD) on visual and prefrontal cortical activity as well as their connectivity during visual working memory updating and related them to the core clinical features of the disorder. Impairment in working memory updating is typically associated with the retention of irrelevant negative information which can lead to persistent depressive mood and abnormal affect. However, performance deficits have been observed in MDD on tasks involving little or no demand on emotion processing, suggesting dysfunctions may also occur at the more basic level of information processing. Yet, it is unclear how various regions in the visual working memory circuit contribute to behavioral changes in MDD. We acquired functional magnetic resonance imaging data from 18 unmedicated participants with MDD and 21 age-matched healthy controls (CTL) while they performed a visual delayed recognition task with neutral faces and scenes as task stimuli. Selective working memory updating was manipulated by inserting a cue in the delay period to indicate which one or both of the two memorized stimuli (a face and a scene) would remain relevant for the recognition test. Our results revealed several key findings. Relative to the CTL group, the MDD group showed weaker postcue activations in visual association areas during selective maintenance of face and scene working memory. Across the MDD subjects, greater rumination and depressive symptoms were associated with more persistent activation and connectivity related to no-longer-relevant task information. Classification of postcue spatial activation patterns of the scene-related areas was also less consistent in the MDD subjects compared to the healthy controls. Such abnormalities appeared to result from a lack of updating effects in postcue functional connectivity between prefrontal and scene-related areas in the MDD group. In sum, disrupted working memory updating in MDD was revealed by

Altered prefrontal correlates of monetary anticipation and outcome in chronic pain.

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Martucci, Katherine T; Borg, Nicholas; MacNiven, Kelly H; Knutson, Brian; Mackey, Sean C

2018-04-04

Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altered reward anticipation and outcome activity within corticostriatal circuits implicated in reward processing. Patients demonstrated lower arousal ratings as compared with controls, but no group differences were observed for valence, positive arousal, or negative arousal ratings. Group fMRI analyses were conducted to determine predetermined region of interest, nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), responses to potential gains, potential losses, reward outcomes, and punishment outcomes. Compared with controls, patients demonstrated similar, although slightly reduced, NAcc activity during gain anticipation. Conversely, patients demonstrated dramatically reduced mPFC activity during gain anticipation-possibly related to lower estimated reward probabilities. Further, patients demonstrated normal mPFC activity to reward outcomes, but dramatically heightened mPFC activity to no-loss (nonpunishment) outcomes. In parallel to NAcc and mPFC responses, patients demonstrated slightly reduced activity during reward anticipation in other brain regions, which included the ventral tegmental area, anterior cingulate cortex, and anterior insular cortex. Together, these results implicate altered corticostriatal processing of monetary rewards in chronic pain.

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

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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).

Reduced dorsolateral prefrontal cortical hemodynamic response in adult obsessive-compulsive disorder as measured by near-infrared spectroscopy during the verbal fluency task

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Hirosawa R

2013-07-01

left and right dorsolateral prefrontal cortex and frontopolar areas. Results: During the verbal fluency task, significant task-related activation was detected in both the OCD group and the controls. Changes in oxygenated hemoglobin concentration in the right dorsolateral prefrontal cortex were significantly smaller in the OCD group than in the controls, but were not statistically significant after correction for multiple comparisons. Conclusion: Patients with OCD have reduced prefrontal, especially right dorsolateral prefrontal, cortical hemodynamic responses as measured by near-infrared spectroscopy during the verbal fluency task. These results support the hypothesis that the dorsolateral prefrontal cortex plays a role in the pathophysiology of OCD. Keywords: functional neuroimaging, near-infrared spectroscopy, obsessive-compulsive disorder, prefrontal hemodynamic response, verbal fluency task, dorsolateral prefrontal cortex

Lesions to polar/orbital prefrontal cortex selectively impair reasoning about emotional material.

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Goel, Vinod; Lam, Elaine; Smith, Kathleen W; Goel, Amit; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

2017-05-01

While it is widely accepted that lesions to orbital prefrontal cortex lead to emotion related disruptions and poor decision-making, there is very little patient data on this issue involving actual logical reasoning tasks. We tested patients with circumscribed, focal lesions largely confined to polar/orbital prefrontal cortex (BA 10 & 11) (N=17) on logical reasoning tasks involving neutral and emotional content, and compared their performance to that of an age and education-matched normal control group (N=22) and a posterior lesion control group (N=24). Our results revealed a significant group by content interaction driven by a selective impairment in the polar/orbital prefrontal cortex group compared to healthy normal controls and to the parietal patient group, in the emotional content reasoning trials. Subsequent analyses of congruent and incongruent reasoning trials indicated that this impairment was driven by the poor performance of patients with polar/orbital lesions in the incongruent trials. We conclude that the polar/orbital prefrontal cortex plays a critical role in filtering emotionally charged content from the material before it is passed on to the reasoning system in lateral/dorsal regions of prefrontal cortex. Where unfiltered content is passed to the reasoning engine, either as a result of pathology (as in the case of our patients) or as a result of individual differences, reasoning performance suffers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prefrontal Hemodynamics of Physical Activity and Environmental Complexity During Cognitive Work.

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McKendrick, Ryan; Mehta, Ranjana; Ayaz, Hasan; Scheldrup, Melissa; Parasuraman, Raja

2017-02-01

The aim of this study was to assess performance and cognitive states during cognitive work in the presence of physical work and in natural settings. Authors of previous studies have examined the interaction between cognitive and physical work, finding performance decrements in working memory. Neuroimaging has revealed increases and decreases in prefrontal oxygenated hemoglobin during the interaction of cognitive and physical work. The effect of environment on cognitive-physical dual tasking has not been previously considered. Thirteen participants were monitored with wireless functional near-infrared spectroscopy (fNIRS) as they performed an auditory 1-back task while sitting, walking indoors, and walking outdoors. Relative to sitting and walking indoors, auditory working memory performance declined when participants were walking outdoors. Sitting during the auditory 1-back task increased oxygenated hemoglobin and decreased deoxygenated hemoglobin in bilateral prefrontal cortex. Walking reduced the total hemoglobin available to bilateral prefrontal cortex. An increase in environmental complexity reduced oxygenated hemoglobin and increased deoxygenated hemoglobin in bilateral prefrontal cortex. Wireless fNIRS is capable of monitoring cognitive states in naturalistic environments. Selective attention and physical work compete with executive processing. During executive processing loading of selective attention and physical work results in deactivation of bilateral prefrontal cortex and degraded working memory performance, indicating that physical work and concomitant selective attention may supersede executive processing in the distribution of mental resources. This research informs decision-making procedures in work where working memory, physical activity, and attention interact. Where working memory is paramount, precautions should be taken to eliminate competition from physical work and selective attention.

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

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Borchert, Robin J; Rittman, Timothy; Passamonti, Luca; Ye, Zheng; Sami, Saber; Jones, Simon P; Nombela, Cristina; Vázquez Rodríguez, Patricia; Vatansever, Deniz; Rae, Charlotte L; Hughes, Laura E; Robbins, Trevor W; Rowe, James B

2016-07-01

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.

The role of rostral prefrontal cortex in prospective memory: a voxel-based lesion study.

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Volle, Emmanuelle; Gonen-Yaacovi, Gil; Costello, Angela de Lacy; Gilbert, Sam J; Burgess, Paul W

2011-07-01

Patients with lesions in rostral prefrontal cortex (PFC) often experience problems in everyday-life situations requiring multitasking. A key cognitive component that is critical in multitasking situations is prospective memory, defined as the ability to carry out an intended action after a delay period filled with unrelated activity. The few functional imaging studies investigating prospective memory have shown consistent activation in both medial and lateral rostral PFC but also in more posterior prefrontal regions and non-frontal regions. The aim of this study was to determine regions that are necessary for prospective memory performance, using the human lesion approach. We designed an experimental paradigm allowing us to assess time-based (remembering to do something at a particular time) and event-based (remembering to do something in a particular situation) prospective memory, using two types of material, words and pictures. Time estimation tasks and tasks controlling for basic attention, inhibition and multiple instructions processing were also administered. We examined brain-behaviour relationships with a voxelwise lesion method in 45 patients with focal brain lesions and 107 control subjects using this paradigm. The results showed that lesions in the right polar prefrontal region (in Brodmann area 10) were specifically associated with a deficit in time-based prospective memory tasks for both words and pictures. This deficit could not be explained by impairments in basic attention, detection, inhibition or multiple instruction processing, and there was also no deficit in event-based prospective memory conditions. In addition to their prospective memory difficulties, these polar prefrontal patients were significantly impaired in time estimation ability compared to other patients. The same region was found to be involved using both words and pictures, suggesting that right rostral PFC plays a material nonspecific role in prospective memory. This is the first

Enhanced prefrontal functional–structural networks to support postural control deficits after traumatic brain injury in a pediatric population

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Ibai Diez

2017-06-01

Full Text Available Traumatic brain injury (TBI affects structural connectivity, triggering the reorganization of structural–functional circuits in a manner that remains poorly understood. We focus here on brain network reorganization in relation to postural control deficits after TBI. We enrolled young participants who had suffered moderate to severe TBI, comparing them to young, typically developing control participants. TBI patients (but not controls recruited prefrontal regions to interact with two separated networks: (1 a subcortical network, including parts of the motor network, basal ganglia, cerebellum, hippocampus, amygdala, posterior cingulate gyrus, and precuneus; and (2 a task-positive network, involving regions of the dorsal attention system, together with dorsolateral and ventrolateral prefrontal regions. We also found that the increased prefrontal connectivity in TBI patients was correlated with some postural control indices, such as the amount of body sway, whereby patients with worse balance increased their connectivity in frontal regions more strongly. The increased prefrontal connectivity found in TBI patients may provide the structural scaffolding for stronger cognitive control of certain behavioral functions, consistent with the observations that various motor tasks are performed less automatically following TBI and that more cognitive control is associated with such actions. Using a new hierarchical atlas whose modules are relevant for both structure and function, we found increased structural and functional connectivity in prefrontal regions in TBI patients as compared to controls, in addition to a general pattern of overall decreased connectivity across the TBI brain. Although this increased prefrontal connectivity reflected interactions between brain areas when participants were at rest, the enhanced connectivity was found to be negatively correlated with active behavior such as postural control performance. Thus our findings, obtained

Noradrenaline and acetylcholine responsiveness of glucose-monitoring and glucose-insensitive neurons in the mediodorsal prefrontal cortex.

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Nagy, Bernadett; Szabó, István; Csetényi, Bettina; Hormay, Edina; Papp, Szilárd; Keresztes, Dóra; Karádi, Zoltán

2014-01-16

The mediodorsal prefrontal cortex (mdPFC), as part of the forebrain glucose-monitoring (GM) system, plays important role in several regulatory processes to control the internal state of the organism and to initiate behavioral outputs accordingly. Little is known, however, about the neurochemical sensitivity of neurons located in this area. Substantial evidence indicates that the locus ceruleus - noradrenaline (NA) projection system and the nucleus basalis magnocellularis - cholinergic projection system regulate behavioral state and state dependent processing of sensory information, various cognitive functions already associated with the mdPFC. The main goal of the present study was to examine noradrenergic and cholinergic responsiveness of glucose-monitoring and glucose-insensitive (GIS) neurons in the mediodorsal prefrontal cortex. One fifth of the neurons tested changed in firing rate to microelectrophoretically applied NA. Responsiveness of the GM cells to this catecholamine proved to be significantly higher than that of the GIS units. Microiontophoretic application of acetylcholine (Ach) resulted in activity changes (predominantly facilitation) of more than 40% of the mdPFC neurons. Proportion of Ach sensitive units among the GM and the GIS neurons was found to be similar. The glucose-monitoring neurons of the mdPFC and their distinct NA and remarkable Ach sensitivity are suggested to be of particular significance in prefrontal control of adaptive behaviors. © 2013 Published by Elsevier B.V.

Differential involvement of left prefrontal cortex in inductive and deductive reasoning.

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Goel, Vinod; Dolan, Raymond J

2004-10-01

While inductive and deductive reasoning are considered distinct logical and psychological processes, little is known about their respective neural basis. To address this issue we scanned 16 subjects with fMRI, using an event-related design, while they engaged in inductive and deductive reasoning tasks. Both types of reasoning were characterized by activation of left lateral prefrontal and bilateral dorsal frontal, parietal, and occipital cortices. Neural responses unique to each type of reasoning determined from the Reasoning Type (deduction and induction) by Task (reasoning and baseline) interaction indicated greater involvement of left inferior frontal gyrus (BA 44) in deduction than induction, while left dorsolateral (BA 8/9) prefrontal gyrus showed greater activity during induction than deduction. This pattern suggests a dissociation within prefrontal cortex for deductive and inductive reasoning.

Effects of neonatal inferior prefrontal and medial temporal lesions on learning the rule for delayed nonmatching-to-sample.

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Málková, L; Bachevalier, J; Webster, M; Mishkin, M

2000-01-01

The ability of rhesus monkeys to master the rule for delayed nonmatching-to-sample (DNMS) has a protracted ontogenetic development, reaching adult levels of proficiency around 4 to 5 years of age (Bachevalier, 1990). To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning (Kowalska, Bachevalier, & Mishkin, 1991; Weinstein, Saunders, & Mishkin, 1988), monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe. Consistent with our previous results (Bachevalier & Mishkin, 1994; Málková, Mishkin, & Bachevalier, 1995), the neonatal medial temporal lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only a mild impairment at 2 years, a finding that also contrasts sharply with the marked effects of the same lesion made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE (Bachevalier & Mishkin, 1994; Málková et al., 1995). The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning.

Lateralized effect of rapid-rate transcranial magnetic stimulation of the prefrontal cortex on mood.

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Pascual-Leone, A; Catalá, M D; Pascual-Leone Pascual, A

1996-02-01

We studied the effects of rapid-rate transcranial magnetic stimulation (rTMS) of different scalp positions on mood. Ten normal volunteers rated themselves before and after rTMS on five analog scales labeled "Tristeza" (Sadness), "Ansiedad" (Anxiety), "Alegria" (Happiness), "Cansancio" (Tiredness), and "Dolor/Malestar" (Pain/Discomfort). rTMS was applied to the right lateral prefrontal, left prefrontal, or midline frontal cortex in trains of 5 seconds' duration at 10 Hz and 110% of the subject's motor threshold intensity. Each stimulation position received 10 trains separated by a 25-second pause. No clinically apparent mood changes were evoked by rTMS to any of the scalp positions in any subject. However, left prefrontal rTMS resulted in a significant increase in the Sadness ratings (Tristeza) and a significant decrease in the Happiness ratings ("Alegria") as compared with right prefrontal and midfrontal cortex stimulation. These results show differential effects of rTMS of left and right prefrontal cortex stimulation on mood and illustrate the lateralized control of mood in normal volunteers.

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

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Maren Strenziok

Full Text Available Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

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Strenziok, Maren; Greenwood, Pamela M; Santa Cruz, Sophia A; Thompson, James C; Parasuraman, Raja

2013-01-01

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to

Genetic predictor of working memory and prefrontal function in women with HIV.

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Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H; Little, Deborah M; Meyer, Vanessa J; Martin, Eileen; Weber, Kathleen; Cohen, Mardge; Maki, Pauline M

2015-02-01

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p women performed significantly worse than HIV-uninfected controls across N-back conditions (p working memory deficits and altered prefrontal function in HIV-infected individuals.

Effects of medial prefrontal cortex lesions in rats on the what-where-when memory of a fear conditioning event.

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Li, Jay-Shake; Hsiao, Kun-Yuan; Chen, Wei-Min

2011-03-17

Previous animal studies have defined the ability to remember the details of what, where, and when of an event as an episodic-like memory to be used to model episodic memory in humans. Numerous findings indicate that the hippocampal-frontal cortical circuitry plays a major part in its neural mechanism. Researchers have intensively studied roles of diverse hippocampus sub-regions using animal models. By contrast, the impact of prefrontal cortex lesions on episodic-like memory in animals is still unknown. Here we show that Wistar rats with bilateral medial prefrontal cortex lesions failed to use the temporal-contextual information to retrieve memory of a fear-conditioning event, indicating impairments in their episodic-like memory. Subsequent experiments excluded alternative interpretations that the manipulation impaired the fear-conditioning per se, or interfered with the sensory preconditioning process. We concluded that damages in this area might impair temporal information processing, or interfere with integrating temporal and contextual elements of fear-conditioning events to form a conjunctive entity. These findings can help understand how the medial prefrontal cortex contributes to episodic-like memory. Copyright © 2010 Elsevier B.V. All rights reserved.

Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

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Weniger Dorothea

2009-12-01

Full Text Available Abstract Objective To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD with deficient haptic perception. Methods Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices. Results We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients. Conclusion PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

Williams Syndrome Hypersociability: A Neuropsychological Study of the Amygdala and Prefrontal Cortex Hypotheses

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Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.

2011-01-01

Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…

Regulation of dopamine synthesis and release in striatal and prefrontal cortical brain slices

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Wolf, M.E.

1986-01-01

Brain slices were used to investigate the role of nerve terminal autoreceptors in modulating dopamine (DA) synthesis and release in striatum and prefrontal cortex. Accumulation of dihydroxyphenylalanine (DOPA) was used as an index of tyrosine hydroxylation in vitro. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed by the DA antagonist sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. The autoreceptor-selective agonist EMD-23-448 also inhibited striatal but not prefrontal DOPA synthesis. DOPA synthesis was stimulated in both brain regions by elevated K + , however only striatal synthesis could be further enhanced by sulpiride. DA release was measured by following the efflux of radioactivity from brain slices prelabeled with [ 3 H]-DA. EMD-23-448 and apomorphine inhibited, while sulpiride enhanced, the K + -evoked overflow of radioactivity from both striatal and prefrontal cortical slices. These findings suggest that striatal DA nerve terminals possess autoreceptors which modulate tyrosine hydroxylation as well as autoreceptors which modulate release. Alternatively, one site may be coupled to both functions through distinct transduction mechanisms. In contrast, autoreceptors on prefrontal cortical terminals appear to regulate DA release but not DA synthesis

Hemodynamic Responses on Prefrontal Cortex Related to Meditation and Attentional Task

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Singh eDeepeshwar

2015-02-01

Full Text Available Recent neuroimaging studies state that meditation increases regional cerebral blood flow (rCBF in the prefrontal cortex (PFC. The present study employed functional near infrared spectroscopy (fNIRS to evaluate the relative hemodynamic changes in prefrontal cortex during a cognitive task. Twenty-two healthy male volunteers with ages between 18 and 30 years (group mean age ± SD; 22.9 ± 4.6 years performed a color-word stroop task before and after 20 minutes of meditation and random thinking. Repeated measures ANOVA was performed followed by a post-hoc analysis with Bonferroni adjustment for multiple comparisons between the mean values of ‘During’ and ‘Post’ with ‘Pre’ state. During meditation there was an increased in oxy-hemoglobin (∆HbO and total hemoglobin (∆THC concentration with reduced deoxy-hemoglobin (∆HbR concentration over the right prefrontal cortex (rPFC, whereas in random thinking there was increased ∆HbR with reduced total hemoglobin concentration on the rPFC. The mean reaction time was shorter in stroop color word task with reduced ∆THC after meditation, suggestive of improved performance and efficiency in task related to attention. Our findings demonstrated that meditation increased cerebral oxygenation and enhanced performance, which was associated with prefrontal cortex activation.

Action control is mediated by prefrontal BDNF and glucocorticoid receptor binding.

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Gourley, Shannon L; Swanson, Andrew M; Jacobs, Andrea M; Howell, Jessica L; Mo, Michelle; Dileone, Ralph J; Koleske, Anthony J; Taylor, Jane R

2012-12-11

Stressor exposure biases decision-making strategies from those based on the relationship between actions and their consequences to others restricted by stimulus-response associations. Chronic stressor exposure also desensitizes glucocorticoid receptors (GR) and diminishes motivation to acquire food reinforcement, although causal relationships are largely not established. We show that a history of chronic exposure to the GR ligand corticosterone or acute posttraining GR blockade with RU38486 makes rodents less able to perform actions based on their consequences. Thus, optimal GR binding is necessary for the consolidation of new response-outcome learning. In contrast, medial prefrontal (but not striatal) BDNF can account for stress-related amotivation, in that selective medial prefrontal cortical Bdnf knockdown decreases break-point ratios in a progressive-ratio task. Knockdown also increases vulnerability to RU38486. Despite the role of BDNF in dendritic spine reorganization, deep-layer spine remodeling does not obviously parallel progressive-ratio response patterns, but treatment with the Na(+)-channel inhibitor riluzole reverses corticosteroid-induced motivational deficits and restores prefrontal BDNF expression after corticosterone. We argue that when prefrontal neurotrophin systems are compromised, and GR-mediated hypothalamic-pituitary-adrenal axis feedback is desensitized (as in the case of chronic stress hormone exposure), amotivation and inflexible maladaptive response strategies that contribute to stress-related mood disorders result.

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources

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Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

2014-01-01

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts—for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts. PMID:23460073

Prefrontal mediation of emotion regulation in social anxiety disorder during laughter perception.

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Kreifelts, Benjamin; Brück, Carolin; Ethofer, Thomas; Ritter, Jan; Weigel, Lena; Erb, Michael; Wildgruber, Dirk

2017-02-01

Social anxiety disorder (SAD) is characterized by negatively biased perception of social cues and deficits in emotion regulation. While negatively biased perception is thought to maintain social anxiety, emotion regulation represents an ability necessary to overcome both biased perception and social anxiety. Here, we used laughter as a social threat in a functional magnetic resonance imaging (fMRI) study to identify cerebral mediators linking SAD with attention and interpretation biases and their modification through cognitive emotion regulation in the form of reappraisal. We found that reappraisal abolished the negative laughter interpretation bias in SAD and that this process was directly mediated through activation patterns of the left dorsolateral prefrontal cortex (DLPFC) serving as a cerebral pivot between biased social perception and its normalization through reappraisal. Connectivity analyses revealed reduced prefrontal control over threat-processing sensory cortices (here: the temporal voice area) during cognitive emotion regulation in SAD. Our results indicate a central role for the left DLPFC in SAD which might represent a valuable target for future research on interventions either aiming to directly modulate cognitive emotion regulation in SAD or to evaluate its potential as physiological marker for psychotherapeutic interventions relying on emotion regulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Responses of medial and ventrolateral prefrontal cortex to interpersonal conflict for resources.

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Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

2014-05-01

Little is known about brain mechanisms recruited during the monitoring and appraisal of social conflicts--for instance, when individuals compete with each other for the same resources. We designed a novel experimental task inducing resource conflicts between two individuals. In an event-related functional magnetic resonance imaging (fMRI) design, participants played with another human participant or against a computer, who across trials chose either different (no-conflict) or the same tokens (conflict trials) in order to obtain monetary gains. In conflict trials, the participants could decide whether they would share the token, and the resulting gain, with the other person or instead keep all points for themselves. Behaviorally, participants shared much more often when playing with a human partner than with a computer. fMRI results demonstrated that the dorsal mediofrontal cortex was selectively activated during human conflicts. This region might play a key role in detecting situations in which self- and social interest are incompatible and require behavioral adjustment. In addition, we found a conflict-related response in the right ventrolateral prefrontal cortex that correlated with measures of social relationship and individual sharing behavior. Taken together, these findings reveal a key role of these prefrontal areas for the appraisal and resolution of interpersonal resource conflicts.

Adaptation to conflict via context-driven anticipatory signals in the dorsomedial prefrontal cortex.

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Horga, Guillermo; Maia, Tiago V; Wang, Pengwei; Wang, Zhishun; Marsh, Rachel; Peterson, Bradley S

2011-11-09

Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial-by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict.

Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli.

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Gingnell, Malin; Bannbers, Elin; Wikström, Johan; Fredrikson, Mats; Sundström-Poromaa, Inger

2013-11-01

Premenstrual disorder (PMDD) affects around 5% of women in childbearing ages. An increased sensitivity in emotion processing areas of the brain to variations in ovarian steroid levels has been suggested as part of the pathophysiology in PMDD, but prior neuroimaging studies of emotion processing are yet inconclusive. Previous behavioral studies of women with PMDD have, however, reported enhanced luteal phase startle responsivity during emotional anticipation. Here we used functional magnetic resonance imaging (fMRI) to investigate central neural circuitry activity during anticipation of, and exposure to, emotional stimuli across the menstrual cycle in women with and without PMDD. As compared to healthy controls, women with PMDD displayed significantly enhanced reactivity in the prefrontal cortex during anticipation of, but not exposure to, negative emotional stimuli during the luteal phase. In PMDD patients, BOLD reactivity during anticipation or viewing of negative emotional stimuli was not dependent on absolute levels of estradiol or progesterone. However, progesterone levels were positively correlated with emotion-induced reactivity in the dorsolateral prefrontal cortex to positive emotional stimuli. These findings suggest that cortical emotional circuitry reactivity during anticipation is altered in PMDD during the luteal phase, which might be part of the pathophysiology behind the emotional symptoms or lack of emotional control reported by women with PMDD. © 2013 Elsevier B.V. and ECNP. All rights reserved.

CT aspects in the diagnosis of tuberculosis in the abdominal and urogenital areas

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Becker, W.; Fischer, H.J.; Uhlenbrock, D.

1983-01-01

The morphologic aspect of abdominal tuberculosis are evaluated by C.T. The necrotising tuberculosis of the genitourinary tract presents course cystic lesions of fluid density. Similar morphologic criteria are seen in ileocoecal tuberculosis. The peritoneal tuberculosis is characterized by large soft tissue masses of a high density which can be found in nearly all areas of the abdomen. The increased morbidity of tuberculosis in peoble from foreign countries living in the Federal Republic of Germany is pointed out. (orig.) [de

tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

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Vanderhasselt, Marie-Anne; De Raedt, Rudi; Brunoni, Andre R; Campanhã, Camila; Baeken, Chris; Remue, Jonathan; Boggio, Paulo S

2013-01-01

Transcranial Direct Current Stimulation (tDCS) is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP) as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation), we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right) prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

The amygdala and ventromedial prefrontal cortex in morality and psychopathy.

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Blair, R J R

2007-09-01

Recent work has implicated the amygdala and ventromedial prefrontal cortex in morality and, when dysfunctional, psychopathy. This model proposes that the amygdala, through stimulus-reinforcement learning, enables the association of actions that harm others with the aversive reinforcement of the victims' distress. Consequent information on reinforcement expectancy, fed forward to the ventromedial prefrontal cortex, can guide the healthy individual away from moral transgressions. In psychopathy, dysfunction in these structures means that care-based moral reasoning is compromised and the risk that antisocial behavior is used instrumentally to achieve goals is increased.

Callosal window between prefrontal cortices: cognitive interaction to retrieve long-term memory.

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Hasegawa, I; Fukushima, T; Ihara, T; Miyashita, Y

1998-08-07

A perceptual image can be recalled from memory without sensory stimulation. However, the neural origin of memory retrieval remains unsettled. To examine whether memory retrieval can be regulated by top-down processes originating from the prefrontal cortex, a visual associative memory task was introduced into the partial split-brain paradigm in monkeys. Long-term memory acquired through stimulus-stimulus association did not transfer via the anterior corpus callosum, a key part interconnecting prefrontal cortices. Nonetheless, when a visual cue was presented to one hemisphere, the anterior callosum could instruct the other hemisphere to retrieve the correct stimulus specified by the cue. Thus, although visual long-term memory is stored in the temporal cortex, memory retrieval is under the executive control of the prefrontal cortex.

Preschool anxiety disorders predict different patterns of amygdala-prefrontal connectivity at school-age.

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Kimberly L H Carpenter

Full Text Available In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation.Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces.A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces.Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders.

Monetary reward activates human prefrontal cortex

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Thut, G.; Roelcke, U.; Nienhusmeier, M.; Missimer, J.; Maguire, R.P.; Leenders, K.L.; Schultz, W.

1997-01-01

We present a rCBF PET activation study, in which we demonstrated that reward processing in humans activates a cortical-subcortical network including dorsolateral prefrontal, orbital frontal, thalamic and midbrain regions. It is suggested that, as found for non-human primates, the basal ganglia-thalamo-cortical system is implicated in reward processing. (author) 1 fig., 3 refs

Protein malnutrition during gestation and early life decreases neuronal size in the medial prefrontal cortex of post-pubertal rats

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Roelf J. Cruz-Rizzolo

2017-12-01

Full Text Available Retrospective studies in human populations indicate that protein deprivation during pregnancy and early life (early protein malnutrition, EPM is associated with cognitive impairments, learning disabilities and may represent a risk factor for the late onset of some psychiatric disorders, fundamentally schizophrenia, a condition where the prefrontal cortex plays an important role. The purpose of this study was to analyze whether EPM affects structural aspects of the rat medial prefrontal cortex (mPFC, such as cortical volume, neuronal density and neuronal soma size, which seem altered in patients with schizophrenia. For this, a rat model of EPM (5% casein from conception to postnatal day 60 was adopted and the rat mPFC volume, total number of neurons and average neuronal volume were evaluated on postnatal day 60 (post-pubertal animals by histo- and immunohistochemical techniques using unbiased stereological analysis. EPM did not alter the number of NeuN+ neurons in the rat mPFC. However, a very significant decrease in mPFC volume and average neuronal size was observed in malnourished rats. Although the present study does not establish causal relationships between malnutrition and schizophrenia, our results may indicate a similar structural phenomenon in these two situations.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

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Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

2015-05-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Near-infrared spectroscopy based neurofeedback of prefrontal cortex activity: a proof-of-concept study

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Beatrix Barth

2016-12-01

Full Text Available Neurofeedback is a promising tool for treatment and rehabilitation of several patient groups. In this proof of principle study, near-infrared spectroscopy (NIRS based neurofeedback of frontal cortical areas was investigated in healthy adults. Main aims were the assessment of learning, the effects on performance in a working memory (n-back task and the impact of applied strategies on regulation.13 healthy participants underwent 8 sessions of NIRS based neurofeedback within two weeks to learn to voluntarily up-regulate hemodynamic activity in prefrontal areas. An n-back task in pre-/post measurements was used to monitor neurocognitive changes. Mean oxygenated hemoglobin (O2Hb amplitudes over the course of the sessions as well as during the n-back task were evaluated. 12 out of 13 participants were able to regulate their frontal hemodynamic response via NIRS neurofeedback. However, no systematic learning effects were observed in frontal O2Hb amplitudes over the training course in our healthy sample. We found an impact of applied strategies in only 5 out of 13 subjects. Regarding the n-back task, neurofeedback appeared to induce more focused and specific brain activation compared to pre-training measurement. NIRS based neurofeedback is a feasible and potentially effective method, with an impact on activation patterns in a working memory task. Ceiling effects might explain the lack of a systematic learning pattern in healthy subjects. Clinical studies are needed to show effects in patients exhibiting pathological deviations in prefrontal function.

Central as well as peripheral attentional bottlenecks in dual-task performance activate lateral prefrontal cortices

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Andre J Szameitat

2016-03-01

Full Text Available Human information processing suffers from severe limitations in parallel processing. In particular, when required to respond to two stimuli in rapid succession, processing bottlenecks may appear at central and peripheral stages of task processing. Importantly, it has been suggested that executive functions are needed to resolve the interference arising at such bottlenecks. The aims of the present study were to test whether central attentional limitations (i.e., bottleneck at the decisional response selection stage as well as peripheral limitations (i.e., bottleneck at response initiation both demand executive functions located in the lateral prefrontal cortex. For this, we re-analysed two previous studies, in which a total of 33 participants performed a dual-task according to the paradigm of the psychological refractory period (PRP during fMRI. In one study (N=17, the PRP task consisted of two two-choice response tasks known to suffer from a central bottleneck (CB group. In the other study (N=16, the PRP task consisted of two simple-response tasks known to suffer from a peripheral bottleneck (PB group. Both groups showed considerable dual-task costs in form of slowing of the second response in the dual-task (PRP effect. Imaging results are based on the subtraction of both single-tasks from the dual-task within each group. In the CB group, the bilateral middle frontal gyri and inferior frontal gyri were activated. Higher activation in these areas was associated with lower dual-task costs. In the PB group, the right middle frontal and inferior frontal gyrus were activated. Here, higher activation was associated with higher dual-task costs. In conclusion we suggest that central and peripheral bottlenecks both demand executive functions located in lateral prefrontal cortices. Differences between the CB and PB groups with respect to the exact prefrontal areas activated and the correlational patterns suggest that the executive functions resolving

Association of cannabis use during adolescence, prefrontal CB1 receptor signaling and schizophrenia

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Adriana eCaballero

2012-05-01

Full Text Available The cannabinoid receptor 1 (CB1R is the G-protein coupled receptor responsible for the majority of the endocannabinoid signaling in the human brain. It is widely distributed in the limbic system, basal ganglia, and cerebellum, which are areas responsible for cognition, memory, and motor control. Because of this widespread distribution, it is not surprising that drugs that co-opt CB1R have expected behavioral outcomes consistent with dysregulated signaling from these areas (e.g. memory loss, cognitive deficits, etc. In the context of this review, we present evidence for the role of CB1R signaling in the prefrontal cortex (PFC, an area involved in executive functions, with emphasis on the developmental regulation of CB1R signaling in the acquisition of mature PFC function. We further hypothesize how alterations of CB1R signaling specifically during adolescent maturation might confer liability to psychiatric disorders.

Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

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Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

2016-09-01

Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.

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.

Altered Communicative Decisions following Ventromedial Prefrontal Lesions

NARCIS (Netherlands)

Stolk, A.; D'Imperio, D.; Pellegrino, G. di; Toni, I.

2015-01-01

Damage to the human ventromedial prefrontal cortex (vmPFC) leads to profound changes in everyday social interactions [1, 2]. Yet, in the lab, vmPFC patients show surprising proficiency in reasoning about other agents [3-8]. These conflicting observations suggest that what vmPFC patients lack in

Aspects of Spatial Economic Processes of Disadvantaged Areas in Hungarian and International Perspective

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KITTI NÉMEDI-KOLLÁR

2015-12-01

Full Text Available The examination of disadvantaged regions goes back to a long history, greatly influenced by the ever-changing natural, economic and human resources. Consequently, while examining the disadvantaged areas, we face new systems of coherences. Today’s regional policy also needs to answer the question whether the spatial development funds of the past have been efficient or not and whether the land use distribution influences the spatial competitiveness or not. As we move towards 2015, we must consider the actual state of delivery of the Millennium Development Goals (MDGs in the Least Developed Countries (LDCs and address the above-mentioned issues in order to realise the international political commitment to leave no one behind. In this paper, we have shown some aspects of spatial economic processes through the example of the Hungarian disadvantaged areas. These issues are timely because the usefulness of the research is important, ranging from rural development to spatial planning and the elaboration of local and regional development strategies. Spatial discrepancies in Hungary cause the disadvantage of rural areas, contributing to their lagging behind compared to the urban areas (Kollár, 2012.

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

Back to front: cerebellar connections and interactions with the prefrontal cortex

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Thomas C Watson

2014-02-01

Full Text Available Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN in awake, behaving rats evokes distinct local field potential (LFP responses (onset latency ~13 ms in the prelimbic (PrL subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anaesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz. Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

Prefrontal serotonin transporter availability is positively associated with the cortisol awakening response

DEFF Research Database (Denmark)

Frokjaer, Vibe Gedsoe; Erritzoe, David; Holst, Klaus Kähler

2013-01-01

higher cortisol responses when exposed to psychosocial stressors relative to high expressing 5-HTTLPR variants. However, it is not clear how the relation between SERT and cortisol output is reflected in the adult brain. We investigated the relation between cortisol response to awakening (CAR) and SERT...... binding in brain regions considered relevant to modify the cortisol awakening response. Methods: thirty-two healthy volunteers underwent in vivo SERT imaging with [11C]DASB-Positron Emission Tomography (PET), genotyping, and performed home-sampling of saliva to assess CAR. Results: CAR, defined...... between CAR and prefrontal SERT binding as tested by an interaction analysis (genotype×CAR). Conclusion: prefrontal SERT binding is positively associated with cortisol response to awakening. We speculate that in mentally healthy individuals prefrontal serotonergic neurotransmission may exert an inhibitory...

Shared and distinct contributions of rostrolateral prefrontal cortex to analogical reasoning and episodic memory retrieval.

Science.gov (United States)

Westphal, Andrew J; Reggente, Nicco; Ito, Kaori L; Rissman, Jesse

2016-03-01

Rostrolateral prefrontal cortex (RLPFC) is widely appreciated to support higher cognitive functions, including analogical reasoning and episodic memory retrieval. However, these tasks have typically been studied in isolation, and thus it is unclear whether they involve common or distinct RLPFC mechanisms. Here, we introduce a novel functional magnetic resonance imaging (fMRI) task paradigm to compare brain activity during reasoning and memory tasks while holding bottom-up perceptual stimulation and response demands constant. Univariate analyses on fMRI data from twenty participants identified a large swath of left lateral prefrontal cortex, including RLPFC, that showed common engagement on reasoning trials with valid analogies and memory trials with accurately retrieved source details. Despite broadly overlapping recruitment, multi-voxel activity patterns within left RLPFC reliably differentiated these two trial types, highlighting the presence of at least partially distinct information processing modes. Functional connectivity analyses demonstrated that while left RLPFC showed consistent coupling with the fronto-parietal control network across tasks, its coupling with other cortical areas varied in a task-dependent manner. During the memory task, this region strengthened its connectivity with the default mode and memory retrieval networks, whereas during the reasoning task it coupled more strongly with a nearby left prefrontal region (BA 45) associated with semantic processing, as well as with a superior parietal region associated with visuospatial processing. Taken together, these data suggest a domain-general role for left RLPFC in monitoring and/or integrating task-relevant knowledge representations and showcase how its function cannot solely be attributed to episodic memory or analogical reasoning computations. © 2015 Wiley Periodicals, Inc.

Neural modeling of prefrontal executive function

Energy Technology Data Exchange (ETDEWEB)

Levine, D.S. [Univ. of Texas, Arlington, TX (United States)

1996-12-31

Brain executive function is based in a distributed system whereby prefrontal cortex is interconnected with other cortical. and subcortical loci. Executive function is divided roughly into three interacting parts: affective guidance of responses; linkage among working memory representations; and forming complex behavioral schemata. Neural network models of each of these parts are reviewed and fit into a preliminary theoretical framework.

Brain injury impairs working memory and prefrontal circuit function

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Colin James Smith

2015-11-01

Full Text Available More than 2.5 million Americans suffer a traumatic brain injury (TBI each year. Even mild to moderate traumatic brain injury causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI, the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI.

Flowers culture and ecological aspects of the areas under petroleum exploitation; Aspectos floristicos e ecologicos das areas submetidas a exploracao de petroleo. Relatorio final

Energy Technology Data Exchange (ETDEWEB)

Amaral, Ieda Leao do; Matos, Francisca Dionisia de Almeida; Lima Filho, Diogenes de Andrade

1995-08-01

This document represents the final report of the brazilian Amazon Research National Institute studies on the ecological aspects of the petroleum exploitation at the Urucu river - State of Amazon - Brazil. The study aimed the determination of the vegetation of the Urucu river, in the areas of PETROBRAS petroleum exploitation activities.

Regulating prefrontal cortex activation

DEFF Research Database (Denmark)

Aznar, Susana; Klein, Anders Bue

2013-01-01

The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings...... of a regulatory effect of the PFC on the emotional control of our actions....

Anterior prefrontal involvement in implicit contextual change detection

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Stefan Pollmann

2009-10-01

Full Text Available Anterior prefrontal cortex is usually associated with high level executive functions. Here, we show that the frontal pole, specifically left lateral frontopolar cortex, is involved in signaling change in implicitly learned spatial contexts, in the absence of conscious change detection. In a variant of the contextual cueing paradigm, participants first learned implicitly contingencies between distractor contexts and target locations. After learning, repeated distractor contexts were paired with new target locations. Left lateral frontopolar (BA10 and superior frontal (BA9 cortices showed selective signal increase for this target location change in repeated displays in an event-related fMRI experiment, which was most pronounced in participants with high contextual facilitation before the change. The data support the view that left lateral frontopolar cortex is involved in signaling contextual change to posterior brain areas as a precondition for adaptive changes of attentional resource allocation. This signaling occurs in the absence of awareness of learned contingencies or contextual change.

Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder

OpenAIRE

Rogers, Tiffany D.; Dickson, Price E.; McKimm, Eric; Heck, Detlef H.; Goldowitz, Dan; Blaha, Charles D.; Mittleman, Guy

2013-01-01

Imaging, clinical and pre-clinical studies have provided ample evidence for a cerebellar involvement in cognitive brain function including cognitive brain disorders, such as autism and schizophrenia. We previously reported that cerebellar activity modulates dopamine release in the mouse medial prefrontal cortex (mPFC) via two distinct pathways: (1) cerebellum to mPFC via dopaminergic projections from the ventral tegmental area [VTA] and (2) cerebellum to mPFC via glutamatergic projections fro...

Altering risky decision-making: Influence of impulsivity on the neuromodulation of prefrontal cortex.

Science.gov (United States)

Cheng, Gordon L F; Lee, Tatia M C

2016-01-01

The prefrontal cortex (PFC) subserves complex cognitive abilities, including risky decision-making; the modulation of this brain area is shown to alter the way people take risks. Yet, neuromodulation of the PFC in relation to risk-taking behavior remains relatively less well-studied. Moreover, the psychological variables that influence such neuromodulation remain poorly understood. To address these issues, 16 participants took part in 3 experimental sessions on separate days. They received: (i) left anodal-right cathodal transcranial direct current stimulation (tDCS); (ii) left cathodal-right anodal stimulation; or (iii) sham stimulation while they completed two risk-taking tasks. They also measured on several cognitive-affective abilities and personality traits. It was revealed that left cathodal-right anodal stimulation led to significantly reduced risk-taking under a context of haste. The reduction of risk-taking (relative to sham) correlated with state and trait impulsivity, such that the effect was larger in more impulsive individuals. For these individuals, the tDCS effect size was considered to be large (generalized partial η(2) > .17). The effect of prefrontal-neuromodulation in reducing risk-taking was influenced by baseline impulsivity, reflecting a state-dependent effect of neuromodulation on the PFC. The results of this study carry important insights into the use of neuromodulation to alter higher cognition.

Postnatal Developmental Trajectories of Neural Circuits in the Primate Prefrontal Cortex: Identifying Sensitive Periods for Vulnerability to Schizophrenia

Science.gov (United States)

Hoftman, Gil D.; Lewis, David A.

2011-01-01

Schizophrenia is a disorder of cognitive neurodevelopment with characteristic abnormalities in working memory attributed, at least in part, to alterations in the circuitry of the dorsolateral prefrontal cortex. Various environmental exposures from conception through adolescence increase risk for the illness, possibly by altering the developmental trajectories of prefrontal cortical circuits. Macaque monkeys provide an excellent model system for studying the maturation of prefrontal cortical circuits. Here, we review the development of glutamatergic and γ-aminobutyric acid (GABA)-ergic circuits in macaque monkey prefrontal cortex and discuss how these trajectories may help to identify sensitive periods during which environmental exposures, such as those associated with increased risk for schizophrenia, might lead to the types of abnormalities in prefrontal cortical function present in schizophrenia. PMID:21505116

A neuropsychological test of belief and doubt: Damage to ventromedial prefrontal cortex increases credulity for misleading advertising

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Erik eAsp

2012-07-01

Full Text Available We have proposed the False Tagging Theory as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the False Tagging Theory to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex would cause a doubt deficit that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the ventromedial prefrontal cortex, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with ventromedial prefrontal cortex damage were (1 more credulous to misleading ads; and (2 showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was corrected by a disclaimer. The evidence is consistent with our proposal that damage to the ventromedial prefrontal cortex disrupts a false tagging mechanism which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging are exposed to persuasive information.

Aberrant prefrontal beta oscillations predict episodic memory encoding deficits in schizophrenia.

Science.gov (United States)

Meconi, Federica; Anderl-Straub, Sarah; Raum, Heidelore; Landgrebe, Michael; Langguth, Berthold; Bäuml, Karl-Heinz T; Hanslmayr, Simon

Verbal episodic memory is one of the core cognitive functions affected in patients with schizophrenia (SZ). Although this verbal memory impairment in SZ is a well-known finding, our understanding about its underlying neurophysiological mechanisms is rather scarce. Here we address this issue by recording brain oscillations during a memory task in a sample of healthy controls and patients with SZ. Brain oscillations represent spectral fingerprints of specific neurocognitive operations and are therefore a promising tool to identify neurocognitive mechanisms that are affected by SZ. Healthy controls showed a prominent suppression of left prefrontal beta oscillatory activity during successful memory formation, which replicates several previous oscillatory memory studies. In contrast, patients failed to exhibit such a left prefrontal beta power suppression. Utilizing a new topographical pattern similarity approach, we further demonstrate that the degree of similarity between a patient's beta power decrease to that of the controls reliably predicted memory performance. This relationship between beta power decreases and memory was such that the patients' memory performance improved as they showed a more similar topographical beta desynchronization pattern compared to that of healthy controls. Together, these findings support left prefrontal beta desynchronization as the spectral fingerprint of verbal episodic memory formation, likely indicating deep semantic processing of verbal material. These findings also demonstrate that left prefrontal beta power suppression (or lack thereof) during memory encoding are a reliable biomarker for the observed encoding impairments in SZ in verbal memory.

Aberrant prefrontal beta oscillations predict episodic memory encoding deficits in schizophrenia

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Federica Meconi

2016-01-01

Full Text Available Verbal episodic memory is one of the core cognitive functions affected in patients with schizophrenia (SZ. Although this verbal memory impairment in SZ is a well-known finding, our understanding about its underlying neurophysiological mechanisms is rather scarce. Here we address this issue by recording brain oscillations during a memory task in a sample of healthy controls and patients with SZ. Brain oscillations represent spectral fingerprints of specific neurocognitive operations and are therefore a promising tool to identify neurocognitive mechanisms that are affected by SZ. Healthy controls showed a prominent suppression of left prefrontal beta oscillatory activity during successful memory formation, which replicates several previous oscillatory memory studies. In contrast, patients failed to exhibit such a left prefrontal beta power suppression. Utilizing a new topographical pattern similarity approach, we further demonstrate that the degree of similarity between a patient's beta power decrease to that of the controls reliably predicted memory performance. This relationship between beta power decreases and memory was such that the patients' memory performance improved as they showed a more similar topographical beta desynchronization pattern compared to that of healthy controls. Together, these findings support left prefrontal beta desynchronization as the spectral fingerprint of verbal episodic memory formation, likely indicating deep semantic processing of verbal material. These findings also demonstrate that left prefrontal beta power suppression (or lack thereof during memory encoding are a reliable biomarker for the observed encoding impairments in SZ in verbal memory.

tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

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Marie-Anne Vanderhasselt

Full Text Available Transcranial Direct Current Stimulation (tDCS is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation, we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

Neuroanatomical Substrates of Executive Functions: Beyond Prefrontal Structures

Science.gov (United States)

Bettcher, Brianne M.; Mungas, Dan; Patel, Nihar; Elofson, Jonathan; Dutt, Shubir; Wynn, Matthew; Watson, Christa L.; Stephens, Melanie; Walsh, Christine M.; Kramer, Joel H.

2016-01-01

Executive functions are often considered lynchpin “frontal lobe tasks”, despite accumulating evidence that a broad network of anterior and posterior brain structures supports them. Using a latent variable modeling approach, we assessed whether prefrontal grey matter volumes independently predict executive function performance when statistically differentiated from global atrophy and individual non-frontal lobar volume contributions. We further examined whether fronto-parietal white matter microstructure underlies and independently contributes to executive functions. We developed a latent variable model to decompose lobar grey matter volumes into a global grey matter factor and specific lobar volumes (i.e. prefrontal, parietal, temporal, occipital) that were independent of global grey matter. We then added mean fractional anisotropy (FA) for the superior longitudinal fasciculus (dorsal portion), corpus callosum, and cingulum bundle (dorsal portion) to models that included grey matter volumes related to cognitive variables in previous analyses. Results suggested that the 2-factor model (shifting/inhibition, updating/working memory) plus an information processing speed factor best explained our executive function data in a sample of 202 community dwelling older adults, and was selected as the base measurement model for further analyses. Global grey matter was related to the executive function and speed variables in all four lobar models, but independent contributions of the frontal lobes were not significant. In contrast, when assessing the effect of white matter microstructure, cingulum FA made significant independent contributions to all three executive function and speed variables and corpus callosum FA was independently related to shifting/inhibition and speed. Findings from the current study indicate that while prefrontal grey matter volumes are significantly associated with cognitive neuroscience measures of shifting/inhibition and working memory in healthy

Neuronal degeneration in the hippocampus and dorsolateral prefrontal cortex in depressive disorder Correlation between 1H-MRS and Minnesota Multiphasic Personality Inventory

Institute of Scientific and Technical Information of China (English)

Jun Xia; Minjie Yang; Yi Lei; Yicheng Zhou

2010-01-01

Previous studies using magnetic resonance imaging(MRI)and functional MRI to study depression have primarily focused on proton magnetic resonance spectroscopy(1H-MRS)appearance in various areas of the brain and volume measurements in the limbic system.However,results have not been consistent.To the best of our knowledge,very little is known about the relationship between 1H-MRS appearance and depression inventory.In the present study,the relationship between 1H-MRS appearance in depressive patients and Minnesota Multiphasic Personality Inventory-2 scale was analyzed.MRI and 1H-MRS exhibited widened sulci and cisterns,as well as an absence of abnormal signals in depressive patients.In addition,N-acetyl aspartate/total creatine ratios in bilateral hippocampi and dorsolateral prefrontal cortex were significantly less in depressive patients than in control subjects(P < 0.01).In contrast,choline-containing compounds/total creatine ratios in the dorsolateral prefrontal cortex were significantly greater in depressive patients than in control subjects(P < 0.01).These ratios significantly and positively correlated with patient total depression scores as assessed using the Minnesota Multiphasic Personality Inventory-2 scale(r=0.934 7,0.878 7,P < 0.01).These results suggested that 1H-MRS could be used to reveal a reduced number of neurons in the hippocampus and dorsolateral prefrontal cortex,as well as altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex,in patients with depressive disorder.Abnormal mechanisms partially reflected severity of depressive disorder.

The role of prefrontal and parietal cortices in esthetic appreciation of representational and abstract art: a TMS study.

Science.gov (United States)

Cattaneo, Zaira; Lega, Carlotta; Gardelli, Chiara; Merabet, Lotfi B; Cela-Conde, Camilo J; Nadal, Marcos

2014-10-01

To explain the biological foundations of art appreciation is to explain one of our species' distinctive traits. Previous neuroimaging and electrophysiological studies have pointed to the prefrontal and the parietal cortex as two critical regions mediating esthetic appreciation of visual art. In this study, we applied transcranial magnetic stimulation (TMS) over the left prefrontal cortex and the right posterior parietal cortex while participants were evaluating whether they liked, and by how much, a particular painting. By depolarizing cell membranes in the targeted regions, TMS transiently interferes with the activity of specific cortical areas, which allows clarifying their role in a given task. Our results show that both regions play a fundamental role in mediating esthetic appreciation. Critically though, the effects of TMS varied depending on the type of art considered (i.e. representational vs. abstract) and on participants' a-priori inclination toward one or the other. Copyright © 2014 Elsevier Inc. All rights reserved.

Cocaine mummies and the pre-frontal reality

International Nuclear Information System (INIS)

Lloyd, Mark Anthony

2001-01-01

Full text: The scientific community frames its world with facts - facts which have been subjected to tests and apparently proven themselves and are therefore proffered by scientists to mankind as things upon which it can rely to steer it safely through life. However, facts are a moveable feast. Time and fresh minds often prove scientific 'facts' wrong. The cocaine mummies seem to indicate that 2000 years ago the Ancient Egyptians had access to both tobacco and cocaine - something previously believed impossible. One part of the German and British scientific community has proven in laboratory tests that the mummies are telling the truth. The rest of the scientific community disputes that truth'. But if the laboratory tests are right, then humanity has to rewrite its entire history. Nuclear communicators have very little credibility with the general public because they represent scientists, who not only are often proven wrong by time but also cannot agree on the truth. At the same time, there are fundamental facts about the human condition that nuclear communicators ignore - to the detriment of their message. Fact: thinking is a learned skill, not an instinct. Fact: language is a learned skill, not an instinct. For humans to follow the positive nuclear argument they must both think and also understand language. But thinking is not the brain's first choice of operation. Fact: the pre-frontal lobe of the brain is the seat of mankind's primitive emotions, including the instinct of fear and the instinct for life. The pre-frontal lobe dominates the way man thinks and speaks. Therefore, nuclear communicators have to learn the skill of mapping their messages to the pre-frontal human reality. This presentation provides practical points for that learning and message mapping exercise. (author)

Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI.

Science.gov (United States)

Diwadkar, V A; Carpenter, P A; Just, M A

2000-07-01

Functional MRI was used to determine how the constituents of the cortical network subserving dynamic spatial working memory respond to two types of increases in task complexity. Participants mentally maintained the most recent location of either one or three objects as the three objects moved discretely in either a two- or three-dimensional array. Cortical activation in the dorsolateral prefrontal (DLPFC) and the parietal cortex increased as a function of the number of object locations to be maintained and the dimensionality of the display. An analysis of the response characteristics of the individual voxels showed that a large proportion were activated only when both the variables imposed the higher level of demand. A smaller proportion were activated specifically in response to increases in task demand associated with each of the independent variables. A second experiment revealed the same effect of dimensionality in the parietal cortex when the movement of objects was signaled auditorily rather than visually, indicating that the additional representational demands induced by 3-D space are independent of input modality. The comodulation of activation in the prefrontal and parietal areas by the amount of computational demand suggests that the collaboration between areas is a basic feature underlying much of the functionality of spatial working memory. Copyright 2000 Academic Press.

abc: The AspectBench Compiler for AspectJ

DEFF Research Database (Denmark)

Allan, Chris; Avgustinov, Pavel; Christensen, Aske Simon

2005-01-01

abc is an extensible, optimising compiler for AspectJ. It has been designed as a workbench for experimental research in aspect-oriented programming languages and compilers. We outline a programme of research in these areas, and we review how abc can help in achieving those research goals...

Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

Science.gov (United States)

Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

2016-10-01

Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

Directional hippocampal-prefrontal interactions during working memory.

Science.gov (United States)

Liu, Tiaotiao; Bai, Wenwen; Xia, Mi; Tian, Xin

2018-02-15

Working memory refers to a system that is essential for performing complex cognitive tasks such as reasoning, comprehension and learning. Evidence shows that hippocampus (HPC) and prefrontal cortex (PFC) play important roles in working memory. The HPC-PFC interaction via theta-band oscillatory synchronization is critical for successful execution of working memory. However, whether one brain region is leading or lagging relative to another is still unclear. Therefore, in the present study, we simultaneously recorded local field potentials (LFPs) from rat ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) and while the rats performed a Y-maze working memory task. We then applied instantaneous amplitudes cross-correlation method to calculate the time lag between PFC and vHPC to explore the functional dynamics of the HPC-PFC interaction. Our results showed a strong lead from vHPC to mPFC preceded an animal's correct choice during the working memory task. These findings suggest the vHPC-leading interaction contributes to the successful execution of working memory. Copyright © 2017. Published by Elsevier B.V.

MicroRNA expression is down-regulated and reorganized in prefrontal cortex of depressed suicide subjects.

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Neil R Smalheiser

Full Text Available Recent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases.The present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9 of antidepressant-free depressed suicide (n = 18 and well-matched non-psychiatric control subjects (n = 17 using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5'-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group.The findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets or indirectly (e.g., by affecting transcription factors.

Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

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Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

2017-02-01

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

Transcranial direct current stimulation over prefrontal cortex diminishes degree of risk aversion.

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Ye, Hang; Chen, Shu; Huang, Daqiang; Wang, Siqi; Jia, Yongmin; Luo, Jun

2015-06-26

Previous studies have established that transcranial direct current stimulation (tDCS) is a powerful technique for manipulating the activity of the human cerebral cortex. Many studies have found that weighing the risks and benefits in decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). We studied whether participants change the balance of risky and safe responses after receiving tDCS applied over the right and left prefrontal cortex. A total of 60 healthy volunteers performed a risk task while they received either anodal tDCS over the right prefrontal cortex, with cathodal over the left; anodal tDCS over the left prefrontal cortex, with cathodal over the right; or sham stimulation. The participants tended to choose less risky options after receiving sham stimulation, demonstrating that the task might be highly influenced by the "wealth effect". There was no statistically significant change after either right anodal/left cathodal or left anodal/right cathodal tDCS, indicating that both types of tDCS impact the participants' degrees of risk aversion, and therefore, counteract the wealth effect. We also found gender differences in the participants' choices. These findings extend the notion that DLPFC activity is critical for risk decision-making. Application of tDCS to the right/left DLPFC may impact a person's attitude to taking risks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anticipatory activity in rat medial prefrontal cortex during a working memory task

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Wenwen Bai; Tiaotiao Liu; Hu Yi; Shuangyan Li; Xin Tian

2012-01-01

Objective Working memory is a key cognitive function in which the prefrontal cortex plays a crucial role.This study aimed to show the firing patterns of a neuronal population in the prefrontal cortex of the rat in a working memory task and to explore how a neuronal ensemble encodes a working memory event.Methods Sprague-Dawley rats were trained in a Y-maze until they reached an 80％ correct rate in a working memory task.Then a 16-channel microelectrode array was implanted in the prefrontal cortex.After recovery,neuronal population activity was recorded during the task,using the Cerebus data-acquisition system.Spatio-temporal trains of action potentials were obtained from the original neuronal population signals.Results During the Y-maze working memory task,some neurons showed significantly increased firing rates and evident neuronal ensemble activity.Moreover,the anticipatory activity was associated with the delayed alternate choice of the upcoming movement.In correct trials,the averaged pre-event firing rate (10.86 ± 1.82 spikes/bin) was higher than the post-event rate (8.17 ± 1.15 spikes/bin) (P ＜0.05).However,in incorrect trials,the rates did not differ.Conclusion The results indicate that the anticipatory activity of a neuronal ensemble in the prefrontal cortex may play a role in encoding working memory events.

Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

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Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

2017-12-13

A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

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Daniel W. Sparks

2018-01-01

Full Text Available Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh and serotonin (5-HT have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.

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Sparks, Daniel W; Tian, Michael K; Sargin, Derya; Venkatesan, Sridevi; Intson, Katheron; Lambe, Evelyn K

2017-01-01

Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

Increased contextual cue utilization with tDCS over the prefrontal cortex during a recognition task

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Pergolizzi, Denise; Chua, Elizabeth F.

2016-01-01

The precise role of the prefrontal and posterior parietal cortices in recognition performance remains controversial, with questions about whether these regions contribute to recognition via the availability of mnemonic evidence or via decision biases and retrieval orientation. Here we used an explicit memory cueing paradigm, whereby external cues probabilistically predict upcoming memoranda as old or new, in our case with 75% validity, and these cues affect recognition decision biases in the direction of the cue. The present study applied bilateral transcranial direct current stimulation (tDCS) over prefrontal or posterior parietal cortex, or sham tDCS, to test the causal role of these regions in recognition accuracy or decision biasing. Participants who received tDCS over prefrontal cortex showed increased cue utilization compared to tDCS over posterior parietal cortex and sham tDCS, suggesting that the prefrontal cortex is involved in processes that contribute to decision biases in memory. PMID:27845032

Perceptual difficulty in source memory encoding and retrieval: prefrontal versus parietal electrical brain activity.

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Kuo, Trudy Y; Van Petten, Cyma

2008-01-01

It is well established that source memory retrieval--remembering relationships between a core item and some additional attribute of an event--engages prefrontal cortex (PFC) more than simple item memory. In event-related potentials (ERPs), this is manifest in a late-onset difference over PFC between studied items which mandate retrieval of a second attribute, and unstudied items which can be immediately rejected. Although some sorts of attribute conjunctions are easier to remember than others, the role of source retrieval difficulty on prefrontal activity has received little attention. We examined memory for conjunctions of object shape and color when color was an integral part of the depicted object, and when monochrome objects were surrounded by colored frames. Source accuracy was reliably worse when shape and color were spatially separated, but prefrontal activity did not vary across the object-color and frame-color conditions. The insensitivity of prefrontal ERPs to this perceptual manipulation of difficulty stands in contrast to their sensitivity to encoding task: deliberate voluntary effort to integrate objects and colors during encoding reduced prefrontal activity during retrieval, but perceptual organization of stimuli did not. The amplitudes of ERPs over parietal cortex were larger for frame-color than object-color stimuli during both study and test phases of the memory task. Individual variability in parietal ERPs was strongly correlated with memory accuracy, which we suggest reflects a contribution of visual working memory to long-term memory. We discuss multiple bottlenecks for source memory performance.

Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: A pilot study

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Feng-Mei Fan; Shu-Ping Tan; Fu-De Yang; Yun-Long Tan; Yan-Li Zhao; Nan Chen; Bin-Bin Li

2013-01-01

People with schizophrenia exhibit impaired social cognitive functions,particularly emotion regulation.Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia,suggesting its important role in emotion processing in patients.We used the resting-state functional connectivity approach,setting a functionally relevant region,the vMPFC,as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients.We found hypo-connectivity between the vMPFC and the medial frontal cortex,right middle temporal lobe (MTL),right hippocampus,parahippocampal cortex (PHC) and amygdala.Further,there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas.Among these connectivity alterations,reduced vMPFCDLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale,while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients.These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia.The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.

Perfusion SPECT studies with mapping of Brodmann areas in differentiating Alzheimer's disease from frontotemporal degeneration syndromes.

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Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

2012-12-01

The aim of this study was to evaluate the contribution of brain perfusion single-photon emission computed tomography (SPECT) studies with mapping of Brodmann areas (BAs) in the differential diagnosis between Alzheimer's disease (AD) and frontotemporal degeneration (FTLD) syndromes. Thirty-nine patients with AD and 73 patients with FTLD syndromes [behavioural variant FTLD (bvFTLD); language variant FTLD (lvFTLD), including semantic dementia (SD) and progressive nonfluent aphasia (PNFA); and corticobasal degeneration (CBD)/progressive supranuclear palsy (PSP) syndromes] underwent brain perfusion SPECT. The NeuroGam software was used for the semiquantitative evaluation of perfusion in BAs of the left (L) and right (R) hemispheres. Compared with those in AD patients, BAs with statistically significant hypoperfusion were found in the prefrontal, orbitofrontal and cingulated cortices and Broca's areas of FTLD and bvFTLD patients; in the temporal and prefrontal cortices and Broca's areas of lvFTLD patients; in the left temporal gyrus of SD patients; in premotor and supplementary motor, prefrontal, orbitofrontal, temporal and anterior cingulated cortices and Broca's areas of PNFA patients; and in the prefrontal, temporal, posterior cingulated and primary and secondary visual cortices of CBD/PSP patients. BA 46R could differentiate AD patients from FTLD and bvFTLD patients; 21L and 25L were found to be independent predictors for lvFTLD in comparison with AD, and 25R, 21L and 23R could differentiate AD patients from PNFA, SD and CBD/PSP patients, respectively. Brain perfusion SPECT with BA mapping in AD and FTLD patients could improve the definition of brain areas that are specifically implicated in these disorders, resulting in a more accurate differential diagnosis.

The prefrontal oxygenation and ventilatory responses at start of one-legged cycling exercise have relation to central command.

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Asahara, Ryota; Matsukawa, Kanji; Ishii, Kei; Liang, Nan; Endo, Kana

2016-11-01

When performing exercise arbitrarily, activation of central command should start before the onset of exercise, but when exercise is forced to start with cue, activation of central command should be delayed. We examined whether the in-advance activation of central command influenced the ventilatory response and reflected in the prefrontal oxygenation, by comparing the responses during exercise with arbitrary and cued start. The breath-by-breath respiratory variables and the prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) were measured during one-legged cycling. Minute ventilation (V̇e) at the onset of arbitrary one-legged cycling was augmented to a greater extent than cued cycling, while end-tidal carbon dioxide tension (ETco 2 ) decreased irrespective of arbitrary or cued start. Symmetric increase in the bilateral prefrontal Oxy-Hb occurred before and at the onset of arbitrary one-legged cycling, whereas such an increase was absent with cued start. The time course and magnitude of the increased prefrontal oxygenation were not influenced by the extent of subjective rating of perceived exertion and were the same as those of the prefrontal oxygenation during two-legged cycling previously reported. Mental imagery or passive performance of the one-legged cycling increased V̇e and decreased ETco 2 Neither intervention, however, augmented the prefrontal Oxy-Hb. The changes in ETco 2 could not explain the prefrontal oxygenation response during voluntary or passive one-legged cycling. Taken together, it is likely that the in-advance activation of central command influenced the ventilatory response by enhancing minute ventilation at the onset of one-legged cycling exercise and reflected in the preexercise increase in the prefrontal oxygenation. Copyright © 2016 the American Physiological Society.

Aprendiendo de las consecuencias de los actos: estudio electrofisiológico del hipocampo, corteza prefrontal y núcleo accumbens

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Jurado Parras, María Teresa

2012-01-01

Programa de Doctorado en Neurociencias La presente Tesis Doctoral se ha centrado en el estudio del papel del hipocampo, la corteza prefrontal medial y el núcleo accumbens en la adquisición del condicionamiento instrumental, del aprendizaje por observación y de la ejecución de tareas instrumentales. Además, se ha estudiado la participación de las sinapsis CA3 ¿ CA1, CA1 ¿ corteza prefrontal medial, corteza prefrontal medial ¿ núcleo accumbens y núcleo accumbens ¿ corteza prefrontal medial e...

Thalamic–hippocampal–prefrontal disruption in relapsing–remitting multiple sclerosis

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Kyle C. Kern

2015-01-01

Conclusions: Hippocampal–thalamic–prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

Orbital prefrontal cortex is required for object-in-place scene memory but not performance of a strategy implementation task.

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Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2007-10-17

The orbital prefrontal cortex is thought to be involved in behavioral flexibility in primates, and human neuroimaging studies have identified orbital prefrontal activation during episodic memory encoding. The goal of the present study was to ascertain whether deficits in strategy implementation and episodic memory that occur after ablation of the entire prefrontal cortex can be ascribed to damage to the orbital prefrontal cortex. Rhesus monkeys were preoperatively trained on two behavioral tasks, the performance of both of which is severely impaired by the disconnection of frontal cortex from inferotemporal cortex. In the strategy implementation task, monkeys were required to learn about two categories of objects, each associated with a different strategy that had to be performed to obtain food reward. The different strategies had to be applied flexibly to optimize the rate of reward delivery. In the scene memory task, monkeys learned 20 new object-in-place discrimination problems in each session. Monkeys were tested on both tasks before and after bilateral ablation of orbital prefrontal cortex. These lesions impaired new scene learning but had no effect on strategy implementation. This finding supports a role for the orbital prefrontal cortex in memory but places limits on the involvement of orbital prefrontal cortex in the representation and implementation of behavioral goals and strategies.

Schizotypal traits in healthy women predict prefrontal activation patterns during a verbal fluency task: a near-infrared spectroscopy study.

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Hori, Hiroaki; Nagamine, Mitsue; Soshi, Takahiro; Okabe, Shigeo; Kim, Yoshiharu; Kunugi, Hiroshi

2008-01-01

Previous functional neuroimaging studies have reported that patients with schizophrenia show reduced prefrontal activation during cognitive tasks whereas patients with schizotypal personality disorder (SPD) show preserved or even increased right prefrontal activation, compared to healthy controls; on the other hand, reduced hemispheric laterality is considered to be common to these two disorders. The aim of this study was to examine the possible association between schizotypal traits at a nonclinical level and prefrontal activation patterns during a letter version of the verbal fluency task (VFT). We examined the relationships of schizotypal traits as measured by the Schizotypal Personality Questionnaire (SPQ) in a nonclinical female population with prefrontal activation patterns during the VFT, using near-infrared spectroscopy. Twenty-seven healthy participants were divided into high (n = 14) and low (n = 13) SPQ groups by the median split of the total SPQ score. Compared to the low SPQ group, the high SPQ group showed significantly larger right prefrontal activation during the performance of the VFT, leading to more bilateral activation. Our results suggest that schizotypal traits at a nonclinical level may be related to relative right prefrontal laterality with overall prefrontal activation being preserved, consistent with previous findings obtained by studies of patients with SPD. 2008 S. Karger AG, Basel.

Major Thought Restructuring: The Roles of Different Prefrontal Cortical Regions.

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Seyed-Allaei, Shima; Avanaki, Zahra Nasiri; Bahrami, Bahador; Shallice, Tim

2017-07-01

An important question for understanding the neural basis of problem solving is whether the regions of human prefrontal cortices play qualitatively different roles in the major cognitive restructuring required to solve difficult problems. However, investigating this question using neuroimaging faces a major dilemma: either the problems do not require major cognitive restructuring, or if they do, the restructuring typically happens once, rendering repeated measurements of the critical mental process impossible. To circumvent these problems, young adult participants were challenged with a one-dimensional Subtraction (or Nim) problem [Bouton, C. L. Nim, a game with a complete mathematical theory. The Annals of Mathematics, 3, 35-39, 1901] that can be tackled using two possible strategies. One, often used initially, is effortful, slow, and error-prone, whereas the abstract solution, once achieved, is easier, quicker, and more accurate. Behaviorally, success was strongly correlated with sex. Using voxel-based morphometry analysis controlling for sex, we found that participants who found the more abstract strategy (i.e., Solvers) had more gray matter volume in the anterior medial, ventrolateral prefrontal, and parietal cortices compared with those who never switched from the initial effortful strategy (i.e., Explorers). Removing the sex covariate showed higher gray matter volume in Solvers (vs. Explorers) in the right ventrolateral prefrontal and left parietal cortex.

Social cognition and prefrontal hemodynamic responses during a working memory task in schizophrenia.

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Pu, Shenghong; Nakagome, Kazuyuki; Yamada, Takeshi; Itakura, Masashi; Yamanashi, Takehiko; Yamada, Sayaka; Masai, Mieko; Miura, Akihiko; Yamauchi, Takahira; Satake, Takahiro; Iwata, Masaaki; Nagata, Izumi; Roberts, David L; Kaneko, Koichi

2016-03-01

Social cognition is an important determinant of functional impairment in schizophrenia, but its relationship with the prefrontal functional abnormalities associated with the condition is still unclear. The present study aimed to explore the relationship between social cognition and prefrontal function in patients with schizophrenia using 52-channel near-infrared spectroscopy (NIRS). Twenty-six patients with schizophrenia and 26 age-, gender-, and intelligence quotient-matched healthy controls (HCs) participated in the study. Hemodynamic responses in the prefrontal and superior temporal cortical regions were assessed during a working memory task using NIRS. Social cognition was assessed using the Social Cognition Screening Questionnaire (SCSQ). The observed hemodynamic responses were significantly reduced in the lateral prefrontal cortex (PFC), the frontopolar cortex, and temporal regions in subjects with schizophrenia compared to HCs. Additionally, lateral PFC hemodynamic responses assessed during the working memory task demonstrated a strong positive correlation with the SCSQ theory of mind (ToM) subscale score even after controlling for working memory performance. These results suggest that ToM integrity is closely related to lateral PFC functional abnormalities found in patients with schizophrenia. In addition, this study provides evidence to suggest that NIRS could be used to identify biomarkers of social cognition function in subjects with schizophrenia.

Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

DEFF Research Database (Denmark)

Kjaerby, Celia; Athilingam, Jegath; Robinson, Sarah E

2016-01-01

Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin...... acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist...... into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings...

Prefrontal involvement in imitation learning of hand actions: effects of practice and expertise.

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Vogt, Stefan; Buccino, Giovanni; Wohlschläger, Afra M; Canessa, Nicola; Shah, N Jon; Zilles, Karl; Eickhoff, Simon B; Freund, Hans-Joachim; Rizzolatti, Giacomo; Fink, Gereon R

2007-10-01

In this event-related fMRI study, we demonstrate the effects of a single session of practising configural hand actions (guitar chords) on cortical activations during observation, motor preparation and imitative execution. During the observation of non-practised actions, the mirror neuron system (MNS), consisting of inferior parietal and ventral premotor areas, was more strongly activated than for the practised actions. This finding indicates a strong role of the MNS in the early stages of imitation learning. In addition, the left dorsolateral prefrontal cortex (DLPFC) was selectively involved during observation and motor preparation of the non-practised chords. This finding confirms Buccino et al.'s [Buccino, G., Vogt, S., Ritzl, A., Fink, G.R., Zilles, K., Freund, H.-J., Rizzolatti, G., 2004a. Neural circuits underlying imitation learning of hand actions: an event-related fMRI study. Neuron 42, 323-334] model of imitation learning: for actions that are not yet part of the observer's motor repertoire, DLPFC engages in operations of selection and combination of existing, elementary representations in the MNS. The pattern of prefrontal activations further supports Shallice's [Shallice, T., 2004. The fractionation of supervisory control. In: Gazzaniga, M.S. (Ed.), The Cognitive Neurosciences, Third edition. MIT Press, Cambridge, MA, pp. 943-956] proposal of a dominant role of the left DLPFC in modulating lower level systems and of a dominant role of the right DLPFC in monitoring operations.

Prefrontal dysfunction in early and continuously treated phenylketonuria

NARCIS (Netherlands)

Stemerdink, NBA; Kalverboer, AF; van der Meere, JJ; de Jong, LW; Slijper, FME; Verkerk, PH; van Spronsen, FJ

1999-01-01

In this study, we tested the hypothesis that patients with early and continuously treated phenylketonuria (PKU) are selectively impaired in cognitive functions dependent on the prefrontal cortex (PFC) over a wide age range. Thirty-six patients with PKU between 8 and 20 years of age and 36 controls

Neural correlates of memory retrieval in the prefrontal cortex.

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Nácher, Verónica; Ojeda, Sabiela; Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Acuña, Carlos

2006-08-01

Working memory includes short-term representations of information that were recently experienced or retrieved from long-term representations of sensory stimuli. Evidence is presented here that working memory activates the same dorsolateral prefrontal cortex neurons that: (a) maintained recently perceived visual stimuli; and (b) retrieved visual stimuli from long-term memory (LTM). Single neuron activity was recorded in the dorsolateral prefrontal cortex while trained monkeys discriminated between two orientated lines shown sequentially, separated by a fixed interstimulus interval. This visual task required the monkey to compare the orientation of the second line with the memory trace of the first and to decide the relative orientation of the second. When the behavioural task required the monkey to maintain in working memory a first stimulus that continually changed from trial to trial, the discharge in these cells was related to the parameters--the orientation--of the memorized item. Then, what the monkey had to recall from memory was manipulated by switching to another task in which the first stimulus was not shown, and had to be retrieved from LTM. The discharge rates of the same neurons also varied depending on the parameters of the memorized stimuli, and their response was progressively delayed as the monkey performed the task. These results suggest that working memory activates dorsolateral prefrontal cortex neurons that maintain parametrical visual information in short-term and LTM, and that the contents of working memory cannot be limited to what has recently happened in the sensory environment.

Basal ganglia impairments in autism spectrum disorder are related to abnormal signal gating to prefrontal cortex.

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Prat, Chantel S; Stocco, Andrea; Neuhaus, Emily; Kleinhans, Natalia M

2016-10-01

Research on the biological basis of autism spectrum disorder has yielded a list of brain abnormalities that are arguably as diverse as the set of behavioral symptoms that characterize the disorder. Among these are patterns of abnormal cortical connectivity and abnormal basal ganglia development. In attempts to integrate the existing literature, the current paper tests the hypothesis that impairments in the basal ganglia's function to flexibly select and route task-relevant neural signals to the prefrontal cortex underpins patterns of abnormal synchronization between the prefrontal cortex and other cortical processing centers observed in individuals with autism spectrum disorder (ASD). We tested this hypothesis using a Dynamic Causal Modeling analysis of neuroimaging data collected from 16 individuals with ASD (mean age=25.3 years; 6 female) and 17 age- and IQ-matched neurotypical controls (mean age=25.6, 6 female), who performed a Go/No-Go test of executive functioning. Consistent with the hypothesis tested, a random-effects Bayesian model selection procedure determined that a model of network connectivity in which basal ganglia activation modulated connectivity between the prefrontal cortex and other key cortical processing centers best fit the data of both neurotypicals and individuals with ASD. Follow-up analyses suggested that the largest group differences were observed for modulation of connectivity between prefrontal cortex and the sensory input region in the occipital lobe [t(31)=2.03, p=0.025]. Specifically, basal ganglia activation was associated with a small decrease in synchronization between the occipital region and prefrontal cortical regions in controls; however, in individuals with ASD, basal ganglia activation resulted in increased synchronization between the occipital region and the prefrontal cortex. We propose that this increased synchronization may reflect a failure in basal ganglia signal gating mechanisms, resulting in a non-selective copying

Reduced but broader prefrontal activity in patients with schizophrenia during n-back working memory tasks: a multi-channel near-infrared spectroscopy study.

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Koike, Shinsuke; Takizawa, Ryu; Nishimura, Yukika; Kinou, Masaru; Kawasaki, Shingo; Kasai, Kiyoto

2013-09-01

Caudal regions of the prefrontal cortex, including the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex, are involved in essential cognitive functions such as working memory. In contrast, more rostral regions, such as the frontopolar cortex (FpC), have integrative functions among cognitive functions and thereby contribute crucially to real-world social activity. Previous functional magnetic resonance imaging studies have shown patients with schizophrenia had different DLPFC activity pattern in response to cognitive load changes compared to healthy controls; however, the spatial relationship between the caudal and rostral prefrontal activation has not been evaluated under less-constrained conditions. Twenty-six patients with schizophrenia and 26 age-, sex-, and premorbid-intelligence-matched healthy controls participated in this study. Hemodynamic changes during n-back working memory tasks with different cognitive loads were measured using multi-channel near-infrared spectroscopy (NIRS). Healthy controls showed significant task-related activity in the bilateral VLPFC and significant task-related decreased activity in the DLPFC, with greater signal changes when the task required more cognitive load. In contrast, patients with schizophrenia showed activation in the more rostral regions, including bilateral DLPFC and FpC. Neither decreased activity nor greater activation in proportion to elevated cognitive load occurred. This multi-channel NIRS study demonstrated that activation intensity did not increase in patients with schizophrenia associated with cognitive load changes, suggesting hypo-frontality as cognitive impairment in schizophrenia. On the other hand, patients had broader prefrontal activity in areas such as the bilateral DLPFC and FpC regions, thus suggesting a hyper-frontality compensatory response. Copyright © 2013 Elsevier Ltd. All rights reserved.

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal-thalamus-hippocampus network.

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Thielen, Jan-Willem; Hong, Donghyun; Rohani Rankouhi, Seyedmorteza; Wiltfang, Jens; Fernández, Guillén; Norris, David G; Tendolkar, Indira

2018-06-01

The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long-term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ-aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face-name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory-related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory-related functional connectivity in a medial prefrontal-thalamus-hippocampus network. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV. Further evidence for regional and behavioral specificity

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Berman, K.F.; Illowsky, B.P.; Weinberger, D.R.

1988-01-01

In previous studies we found that patients with chronic schizophrenia had lower regional cerebral blood flow (rCBF) in dorsolateral prefrontal cortex (DLPFC) than did normal subjects during performance of the Wisconsin Card Sort Test, an abstract reasoning task linked to DLPFC function. This was not the case during less complex tasks. To examine further whether this finding represented regionally circumscribed pathophysiology or a more general correlate of abstract cognition, 24 medication-free patients and 25 age- and sex-matched normal control subjects underwent rCBF measurements with the xenon 133 technique while they performed two tasks: Raven's Progressive Matrices (RPM) and an active baseline control task. While performing RPM, normal subjects activated posterior cortical areas over baseline, but did not activate DLPFC, as had been seen during the Wisconsin Card Sort Test. Like normal subjects, patients showed maximal rCBF elevations posteriorly and, moreover, they had no significant DLPFC or other cortical deficit while performing RPM. These results suggest that DLPFC dysfunction in schizophrenia is linked to pathophysiology of a regionally specific neural system rather than to global cortical dysfunction, and that this pathophysiology is most apparent under prefrontally specific cognitive demand

Prefrontal cortex volume reductions and tic inhibition are unrelated in uncomplicated GTS adults.

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Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Brandt, Valerie; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

2014-01-01

Tics in Gilles de la Tourette syndrome (GTS) are repetitive patterned movements, resembling spontaneous motor behaviour, but escaping voluntary control. Previous studies hypothesised relations between structural alterations in prefrontal cortex of GTS adults and tic severity using voxel-based morphometry (VBM), but could not demonstrate a significant association. The relation between prefrontal cortex structure and tic inhibition has not been investigated. Here, we used VBM to examine 14 GTS adults without associated comorbidities, and 15 healthy controls. We related structural alterations in GTS to clinical measures of tic severity and tic control. Grey matter volumes in the right inferior frontal gyrus and the left frontal pole were reduced in patients relative to healthy controls. These changes were not related to tic severity and tic inhibition. Prefrontal grey matter volume reductions in GTS adults are not related to state measures of tic phenomenology. © 2013.

Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents.

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Tan, Zhibing; Robinson, Heath L; Yin, Dong-Min; Liu, Yu; Liu, Fang; Wang, Hongsheng; Lin, Thiri W; Xing, Guanglin; Gan, Lin; Xiong, Wen-Cheng; Mei, Lin

2018-04-18

Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

Dorsolateral Prefrontal Contributions to Human Intelligence

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Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

2012-01-01

Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control functions for human intelligence, the necessity of the dorsolateral prefrontal cortex (dlPFC) for key competencies of general intelligence and executive function remains to be well established. Here we studied human brain lesion patients with dlPFC lesions to investigate whether this region is computationally necessary for performance on neuropsychological tests of general intelligence and executive function, administering the Wechsler Adult Intelligence Scale (WAIS) and subtests of the Delis Kaplan Executive Function System (D-KEFS) to three groups: dlPFC lesions (n = 19), non-dlPFC lesions (n = 152), and no brain lesions (n = 55). The key results indicate that: (1) patients with focal dlPFC damage exhibit lower scores, at the latent variable level, than controls in general intelligence (g) and executive function; (2) dlPFC patients demonstrate lower scores than controls in several executive measures; and (3) these latter differences are no longer significant when the pervasive influence of the general factor of intelligence (g) is statistically removed. The observed findings support a central role for the dlPFC in general intelligence and make specific recommendations for the interpretation and application of the WAIS and D-KEFS to the study of high-level cognition in health and disease. PMID:22634247

Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms : An Exploratory Study

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Dlabac-de Lange, Jozarni J.; Liemburg, Edith J.; Bais, Leonie; van de Poel-Mustafayeva, Aida T.; de Lange-de Klerk, Elly S. M.; Knegtering, Henderikus; Aleman, Andre

2017-01-01

Background: Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. Objective: This study aims to investigate changes in the levels of glutamate and glutamine (Glx,

[Measurement of the frontal and prefrontal lobe volumes in children with malnutrition by three dimensional magnetic resonance imaging scan].

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Kanemura, Hideaki; Aihara, Masao; Nakazawa, Shinpei

2002-09-01

To evaluate the effects of malnutrition in early life on the growth of the frontal and prefrontal lobes, we quantitatively measured the volumes of the frontal and prefrontal lobes by three dimensional (3-D) MRI in three children (1 year 2 months to 2 years 5 months) with malnutrition. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. The data obtained were compared with those of 16 normal subjects (13 children aged 5 months to 14 years, and 3 adults aged 27 to 39 years). The volumes of the frontal and prefrontal lobes in the subjects were smaller compared with age matched controls. The results suggest that malnutrition in early life affects the growth of the frontal and prefrontal lobes.

Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation.

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Tomasino, Barbara; Fabbro, Franco

2016-02-01

Mindfulness meditation is a form of attention control training. The training exercises the ability to repeatedly focus attention. We addressed the activation changes related to an 8-weeks mindfulness-oriented focused attention meditation training on an initially naïve subject cohort. Before and after training participants underwent an fMRI experiment, thus, although not strictly a cross over design, they served as their internal own control. During fMRI they exercised focused attention on breathing and body scan as compared to resting. We found increased and decreased activation in different parts of the prefrontal cortex (PFC) by comparing pre- vs. post-mindfulness training (MT) during breathing and body scan meditation exercises that were compared against their own resting state. In the post-MT (vs. pre-MT) meditation increased activation in the right dorsolateral PFC and in the left caudate/anterior insula and decreased activation in the rostral PFC and right parietal area 3b. Thus a brief mindfulness training caused increased activation in areas involved in sustaining and monitoring the focus of attention (dorsolateral PFC), consistent with the aim of mindfulness that is exercising focused attention mechanisms, and in the left caudate/anterior insula involved in attention and corporeal awareness and decreased activation in areas part of the "default mode" network and is involved in mentalizing (rostral PFC), consistent with the ability trained by mindfulness of reducing spontaneous mind wandering. Copyright © 2015 Elsevier Inc. All rights reserved.

The flexible use of multiple cue relationships in spatial navigation : A comparison of water maze performance following hippocampal, medial septal, prefrontal cortex, or posterior parietal cortex lesions

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Compton, DM; Griffith, HR; McDaniel, WF; Foster, RA; Davis, BK

Rats prepared with lesions of the prefrontal cortex, posterior parietal cortex, hippocampus, or medial septal area were tested for acquisition of a number of variations of the open-field water maze using a version of place learning assessment described by Eichenbaum, Stewart, and Morris (1991).

Distorted images of one's own body activates the prefrontal cortex and limbic/paralimbic system in young women: a functional magnetic resonance imaging study.

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Kurosaki, Mitsuhaya; Shirao, Naoko; Yamashita, Hidehisa; Okamoto, Yasumasa; Yamawaki, Shigeto

2006-02-15

Our aim was to study the gender differences in brain activation upon viewing visual stimuli of distorted images of one's own body. We performed functional magnetic resonance imaging on 11 healthy young men and 11 healthy young women using the "body image tasks" which consisted of fat, real, and thin shapes of the subject's own body. Comparison of the brain activation upon performing the fat-image task versus real-image task showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala in the women, and significant activation of the right occipital lobe including the primary and secondary visual cortices in the men. Comparison of brain activation upon performing the thin-image task versus real-image task showed significant activation of the left prefrontal cortex, left limbic area including the cingulate gyrus and paralimbic area including the insula in women, and significant activation of the occipital lobe including the left primary and secondary visual cortices in men. These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion, whereas men tend to perceive distorted images of their own bodies by object visual processing and spatial visual processing.

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

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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.

Prefrontal gray matter volume mediates genetic risks for obesity.

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Opel, N; Redlich, R; Kaehler, C; Grotegerd, D; Dohm, K; Heindel, W; Kugel, H; Thalamuthu, A; Koutsouleris, N; Arolt, V; Teuber, A; Wersching, H; Baune, B T; Berger, K; Dannlowski, U

2017-05-01

Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults

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Meer, van Floor; Laan, van der Laura N.; Viergever, Max A.; Adan, Roger A.H.; Smeets, Paul A.M.

2017-01-01

Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is

Electrophysiological evidence during episodic prospection implicates medial prefrontal and bilateral middle temporal gyrus.

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Hsu, Chia-Fen; Sonuga-Barke, Edmund J S

2016-08-01

fMRI studies have implicated the medial prefrontal cortex and medial temporal lobe, components of the default mode network (DMN), in episodic prospection. This study compared quantitative EEG localized to these DMN regions during prospection and during resting and while waiting for rewards. EEG was recorded in twenty-two adults while they were asked to (i) envision future monetary episodes; (ii) wait for rewards and (iii) rest. Activation sources were localized to core DMN regions. EEG power and phase coherence were compared across conditions. Prospection, compared to resting and waiting, was associated with reduced power in the medial prefrontal gyrus and increased power in the bilateral medial temporal gyrus across frequency bands as well as greater phase synchrony between these regions in the delta band. The current quantitative EEG analysis confirms prior fMRI research suggesting that medial prefrontal and medial temporal gyrus interactions are central to the capacity for episodic prospection. Copyright © 2016 Elsevier B.V. All rights reserved.

Ventromedial prefrontal cortex, adding value to autobiographical memories.

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Lin, Wen-Jing; Horner, Aidan J; Burgess, Neil

2016-06-24

The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants' memories when they were recalling and evaluating these items. An unrelated modulation by the participant's familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information, and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories.

Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory.

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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

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

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Asensio, S.; Goldstein, R.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F.; Volkow, N.D.; Goldstein, R.Z.

2010-01-01

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with ( 11 C)raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

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Asensio, S.; Goldstein, R.; Asensio, S.; Romero, M.J.; Romero, F.J.; Wong, C.T.; Alia-Klein, N.; Tomasi, D.; Wang, G.-J.; Telang, F..; Volkow, N.D.; Goldstein, R.Z.

2010-05-01

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.

Improved Prefrontal Activity and Chewing Performance as Function of Wearing Denture in Partially Edentulous Elderly Individuals: Functional Near-Infrared Spectroscopy Study

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Kamiya, Kazunobu; Narita, Noriyuki; Iwaki, Sunao

2016-01-01

The purpose of this study was to elucidate the effects of wearing a denture on prefrontal activity during chewing performance. We specifically examined that activity in 12 elderly edentulous subjects [63.1±6.1 years old (mean ± SD)] and 12 young healthy controls (22.1±2.3 years old) using functional near-infrared spectroscopy (fNIRS) in order to evaluate the quality of prefrontal functionality during chewing performance under the conditions of wearing a denture and tooth loss, and then compared the findings with those of young healthy controls. fNIRS and electromyography were used simultaneously to detect prefrontal and masticatory muscle activities during chewing, while occlusal force and masticatory score were also examined by use of a food intake questionnaire. A significant increase in prefrontal activity was observed during chewing while wearing a denture, which was accompanied by increased masticatory muscle activity, occlusal force, and masticatory score, as compared with the tooth loss condition. Prefrontal activation during chewing while wearing a denture in the elderly subjects was not much different from that in the young controls. In contrast, tooth loss in the elderly group resulted in marked prefrontal deactivation, accompanied by decreased masticatory muscle activity, occlusal force, and masticatory score, as compared with the young controls. We concluded that intrinsic prefrontal activation during chewing with a denture may prevent prefrontal depression induced by tooth loss in elderly edentulous patients. PMID:27362255

Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

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Fazio, Leonardo; Logroscino, Giancarlo; Taurisano, Paolo; Amico, Graziella; Quarto, Tiziana; Antonucci, Linda Antonella; Barulli, Maria Rosaria; Mancini, Marina; Gelao, Barbara; Ferranti, Laura; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2016-01-01

Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions. Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia. Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior. These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

Prefrontal Activity and Connectivity with the Basal Ganglia during Performance of Complex Cognitive Tasks Is Associated with Apathy in Healthy Subjects.

Directory of Open Access Journals (Sweden)

Leonardo Fazio

Full Text Available Convergent evidence indicates that apathy affects cognitive behavior in different neurological and psychiatric conditions. Studies of clinical populations have also suggested the primary involvement of the prefrontal cortex and the basal ganglia in apathy. These brain regions are interconnected at both the structural and functional levels and are deeply involved in cognitive processes, such as working memory and attention. However, it is unclear how apathy modulates brain processing during cognition and whether such a modulation occurs in healthy young subjects. To address this issue, we investigated the link between apathy and prefrontal and basal ganglia function in healthy young individuals. We hypothesized that apathy may be related to sub-optimal activity and connectivity in these brain regions.Three hundred eleven healthy subjects completed an apathy assessment using the Starkstein's Apathy Scale and underwent fMRI during working memory and attentional performance tasks. Using an ROI approach, we investigated the association of apathy with activity and connectivity in the DLPFC and the basal ganglia.Apathy scores correlated positively with prefrontal activity and negatively with prefrontal-basal ganglia connectivity during both working memory and attention tasks. Furthermore, prefrontal activity was inversely related to attentional behavior.These results suggest that in healthy young subjects, apathy is a trait associated with inefficient cognitive-related prefrontal activity, i.e., it increases the need for prefrontal resources to process cognitive stimuli. Furthermore, apathy may alter the functional relationship between the prefrontal cortex and the basal ganglia during cognition.

Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment.

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Vermeij, Anouk; Kessels, Roy P C; Heskamp, Linda; Simons, Esther M F; Dautzenberg, Paul L J; Claassen, Jurgen A H R

2017-02-01

Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole-group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity.

c-Fos immunoreactivity in prefrontal, basal ganglia and limbic areas of the rat brain after central and peripheral administration of ethanol and its metabolite acetaldehyde.

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Kristen N. Segovia

2013-05-01

Full Text Available Considerable evidence indicates that the metabolite of ethanol (EtOH, acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase, and also centrally by catalase. EtOH and acetaldehyde show differences in their behavioral effects depending upon the route of administration. In terms of their effects on motor activity and motivated behaviors, when administered peripherally acetaldehyde tends to be more potent than EtOH but shows very similar potency administered centrally. Since dopamine (DA rich areas have an important role in regulating both motor activity and motivation, the present studies were undertaken to compare the effects of central (intraventricular, ICV and peripheral (intraperitoneal, IP administration of EtOH and acetaldehyde on a cellular marker of brain activity, c-Fos immunoreactivity, in DA innervated areas. Male Sprague-Dawley rats received an IP injection of vehicle, EtOH (0.5 or 2.5 g/kg or acetaldehyde (0.1 or 0.5 g/kg or an ICV injection of vehicle, EtOH or acetaldehyde (2.8 or 14.0 µmoles. IP administration of EtOH minimally induced c-Fos in some regions of the prefrontal cortex and basal ganglia, mainly at the low dose (0.5 g/kg, while IP acetaldehyde induced c-Fos in virtually all the structures studied at both doses. Acetaldehyde administered centrally increased c-Fos in all areas studied, a pattern that was very similar to EtOH. Thus, IP administered acetaldehyde was more efficacious than EtOH at inducing c-Fos expression. However, the general pattern of c-Fos induction promoted by ICV EtOH and acetaldehyde was similar. These results are consistent with the pattern observed in behavioral studies in which both substances produced the same magnitude of effect when injected centrally, and produced differences in potency after peripheral administration.

Differential contribution of left and right prefrontal cortex to associative cued-recall memory: a parametric PET study.

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Lepage, Martin

2004-03-01

Several brain imaging studies have implicated prefrontal regions bilaterally during cued-recall memory tasks and yet the functional significance of these regions remains poorly understood. Using PET, we examined the neural activity in prefrontal regions of 15 subjects while they performed three cued-recall tasks differing in pre-experimental semantic associations between cues and targets. This manipulation produced varying levels of retrieval performance when one member (a semantic category name) of the triad was used as a cue for the retrieval of the other two members. The percentage of items correctly recalled was 10, 46, and 70 in the low, medium, and high cued-recall conditions, respectively. Linear contrast analyses of the PET data identified brain regions where neural activity varied with the number of items retrieved from memory. A left lateral prefrontal region showed maximal activity during the high cued-recall condition, which likely reflects processes involved in retrieval success and possibly in the generation of memory responses. Three right prefrontal regions (anterior and dorsolateral) showed maximal activity during the low cued-recall condition, which likely reflects processes involved in memory search/monitoring. These findings add further support for a bilateral prefrontal contribution to memory cued-recall tasks and point to differential roles of the two hemispheres.

GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

Science.gov (United States)

Akbarian, S.; Huntsman, M. M.; Kim, J. J.; Tafazzoli, A.; Potkin, S. G.; Bunney, W. E. Jr; Jones, E. G.; Bloom, F. E. (Principal Investigator)

1995-01-01

The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of

Attentional set-shifting deficit in Parkinson's disease is associated with prefrontal dysfunction: an FDG-PET study.

Directory of Open Access Journals (Sweden)

Yoichi Sawada

Full Text Available The attentional set-shifting deficit that has been observed in Parkinson's disease (PD has long been considered neuropsychological evidence of the involvement of meso-prefrontal and prefrontal-striatal circuits in cognitive flexibility. However, recent studies have suggested that non-dopaminergic, posterior cortical pathologies may also contribute to this deficit. Although several neuroimaging studies have addressed this issue, the results of these studies were confounded by the use of tasks that required other cognitive processes in addition to set-shifting, such as rule learning and working memory. In this study, we attempted to identify the neural correlates of the attentional set-shifting deficit in PD using a compound letter task and 18F-fluoro-deoxy-glucose (FDG positron emission tomography during rest. Shift cost, which is a measure of attentional set-shifting ability, was significantly correlated with hypometabolism in the right dorsolateral prefrontal cortex, including the putative human frontal eye field. Our results provide direct evidence that dysfunction in the dorsolateral prefrontal cortex makes a primary contribution to the attentional set-shifting deficit that has been observed in PD patients.

In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users

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Frokjaer, Vibe Gedsoe; Erritzoe, David; Holst, Klaus Kähler

2014-01-01

awakening response (CAR). Here, we tested (1) if such a correlation persists in a human model of chronic serotonin depletion, namely in 3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') users, and (2) if CAR differed between MDMA users (N = 18) and non-using healthy volunteers (N = 32). Participants...... underwent SERT brain imaging with [11C]DASB-PET, and performed home-sampling of CAR, defined as the area under curve with respect to cortisol increase from awakening level. When adjusting for age and group, CAR was positively coupled to prefrontal SERT binding (p = 0.006) and MDMA users showed significantly...... higher CAR than the control group (p = 0.0003). In conclusion, our data confirm the recently described positive association between prefrontal SERT binding and CAR, this time in a human model of serotonin deficiency. Also, we find that CAR was higher in MDMA users relative to non-users. We suggest...

Prefrontal cortex damage abolishes brand-cued changes in cola preference.

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Koenigs, Michael; Tranel, Daniel

2008-03-01

Human decision-making is remarkably susceptible to commercial advertising, yet the neurobiological basis of this phenomenon remains largely unexplored. With a series of Coke and Pepsi taste tests we show that patients with damage specifically involving ventromedial prefrontal cortex (VMPC), an area important for emotion, did not demonstrate the normal preference bias when exposed to brand information. Both comparison groups (neurologically normal adults and lesion patients with intact VMPC) preferred Pepsi in a blind taste test, but in subsequent taste tests that featured brand information ('semi-blind' taste tests), both comparison groups' preferences were skewed toward Coke, illustrating the so-called 'Pepsi paradox'. Like comparison groups, the VMPC patients preferred Pepsi in the blind taste test, but unlike comparison groups, the VMPC patients maintained their Pepsi preference in the semi-blind test. The result that VMPC damage abolishes the 'Pepsi paradox' suggests that the VMPC is an important part of the neural substrate for translating commercial images into brand preferences.

Visual attention: Linking prefrontal sources to neuronal and behavioral correlates.

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Clark, Kelsey; Squire, Ryan Fox; Merrikhi, Yaser; Noudoost, Behrad

2015-09-01

Attention is a means of flexibly selecting and enhancing a subset of sensory input based on the current behavioral goals. Numerous signatures of attention have been identified throughout the brain, and now experimenters are seeking to determine which of these signatures are causally related to the behavioral benefits of attention, and the source of these modulations within the brain. Here, we review the neural signatures of attention throughout the brain, their theoretical benefits for visual processing, and their experimental correlations with behavioral performance. We discuss the importance of measuring cue benefits as a way to distinguish between impairments on an attention task, which may instead be visual or motor impairments, and true attentional deficits. We examine evidence for various areas proposed as sources of attentional modulation within the brain, with a focus on the prefrontal cortex. Lastly, we look at studies that aim to link sources of attention to its neuronal signatures elsewhere in the brain. Copyright © 2015. Published by Elsevier Ltd.

Guanfacine modulates the emotional biasing of amygdala-prefrontal connectivity for cognitive control.

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Schulz, Kurt P; Clerkin, Suzanne M; Newcorn, Jeffrey H; Halperin, Jeffrey M; Fan, Jin

2014-09-01

Functional interactions between amygdala and prefrontal cortex provide a cortical entry point for emotional cues to bias cognitive control. Stimulation of α2 adrenoceptors enhances the prefrontal control functions and blocks the amygdala-dependent encoding of emotional cues. However, the impact of this stimulation on amygdala-prefrontal interactions and the emotional biasing of cognitive control have not been established. We tested the effect of the α2 adrenoceptor agonist guanfacine on psychophysiological interactions of amygdala with prefrontal cortex for the emotional biasing of response execution and inhibition. Fifteen healthy adults were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task following administration of oral guanfacine (1mg) and placebo in a double-blind, counterbalanced design. Happy, sad, and neutral faces served as trial cues. Guanfacine moderated the effect of face emotion on the task-related functional connectivity of left and right amygdala with left inferior frontal gyrus compared to placebo, by selectively reversing the functional co-activation of the two regions for response execution cued by sad faces. This shift from positively to negatively correlated activation for guanfacine was associated with selective improvements in the relatively low accuracy of responses to sad faces seen for placebo. These results demonstrate the importance of functional interactions between amygdala and inferior frontal gyrus to both bottom-up biasing of cognitive control and top-down control of emotional processing, as well as for the α2 adrenoceptor-mediated modulation of these processes. These mechanisms offer a possibile method to address the emotional reactivity that is common to several psychiatric disorders. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight.

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Anders, Silke; Eippert, Falk; Wiens, Stefan; Birbaumer, Niels; Lotze, Martin; Wildgruber, Dirk

2009-11-01

Affective neuroscience has been strongly influenced by the view that a 'feeling' is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients' response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients' phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with

Medial prefrontal cortex involvement in the expression of extinction and ABA renewal of instrumental behavior for a food reinforcer.

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Eddy, Meghan C; Todd, Travis P; Bouton, Mark E; Green, John T

2016-02-01

Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of

Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic acid animal model of autism

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Tania Rinaldi

2008-10-01

Full Text Available The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. These excitatory connections are more plastic displaying enhanced long-term potentiation of the strength of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions in the brain, and stands in contrast to the hypo-functionality that is normally proposed in this region to explain some of the autistic symptoms. We propose that a number of deficits in autism such as sociability, attention, multi-tasking and repetitive behaviours, should be re-interpreted in the light of a hyper-functional prefrontal cortex.

A study of 1H-MR spectroscopy in the prefrontal cortex and amygdala of heroine abusers

International Nuclear Information System (INIS)

Yang Lanying; Wang Yarong; Li Qiang; Xiong Xiaoshuang; Wang Wei; Zhao Wei; Bai Yunliang

2009-01-01

Objective: To explore the characteristic findings of 1 H-MR spectroscopy ( 1 H-MRS) in the prefrontal cortex and amygdala of patients with heroine dependence (HD), and the relationship to total cumulative dose of inhaled heroine. Methods: Fourteen male HD patients and 12 healthy controls (HC) underwent 1 H-MRS at the prefrontal cortex and amygdala regions. The total cumulative in haled heroin dose was (852±341) g in HD. Ratios of N-acetylaspartate/creatine(NAA/Cr) and choline/creatine (Cho/Cr) were respectively measured in the prefrontal cortex and bilateral amygdale regions. The student's t test and the linear correlation were employed for statistical analysis. Results: Compared to HC group, HD patients had a significant lower ratio of NAA/Cr in the prefrontal cortex (1.44±0.46 vs 1.50±0.75, t=1.77, P< 0.05), left amygdala region (1.32±0.08 vs 1.42±0.08, t=3.41, P<0.05), and right amygdala region (1.34±0.09 vs 1.44±0.10, t=2.63, P<0.05), the HD patients had a significant increased ratio of Cho/Cr in the prefrontal cortex (0.92±0.06 vs 0.86±0.08, t=2.31, P<0.05), left amygdala region (1.20±0.12 vs 1.07±0.04, t=3.60, P<0.05) and right amygdala region(1.26±0.15 vs 1.12±0.11, t=2.60, P<0.05). There was a negative linear correlation between the total cumulative inhaled heroine dose and the ratio of NAA/Cr in the prefrontal cortex (r=-0.9159, P<0.01), left amygdala region( r= -0.8756, P<0.01), and right amygdala region (r=-0.9399, P<0.01) respectively. Conclusions: The study indicates that neuronal damage and glial proliferation may occur in the prefrontal cortex and amygdala region, which suggests the abnormalities of executive function and emotion in patients with HD. A relationship exists between the heroin-induced metabolic abnormality and the total cumulative dose of inhaled heroine. (authors)

Prefrontal activity and impaired memory encoding strategies in schizophrenia.

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Guimond, Synthia; Hawco, Colin; Lepage, Martin

2017-08-01

Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome. Copyright © 2017. Published by Elsevier Ltd.

Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task.

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Méndez-Couz, Marta; Conejo, Nélida M; Vallejo, Guillermo; Arias, Jorge L

2015-01-01

Several studies suggest a prefrontal cortex involvement during the acquisition and consolidation of spatial memory, suggesting an active modulating role at late stages of acquisition processes. Recently, we have reported that the prelimbic and infralimbic areas of the prefrontal cortex, among other structures, are also specifically involved in the late phases of spatial memory extinction. This study aimed to evaluate whether the inactivation of the prelimbic area of the prefrontal cortex impaired spatial memory extinction. For this purpose, male Wistar rats were implanted bilaterally with cannulae into the prelimbic region of the prefrontal cortex. Animals were trained during 5 consecutive days in a hidden platform task and tested for reference spatial memory immediately after the last training session. One day after completing the training task, bilateral infusion of the GABAA receptor agonist Muscimol was performed before the extinction protocol was carried out. Additionally, cytochrome c oxidase histochemistry was applied to map the metabolic brain activity related to the spatial memory extinction under prelimbic cortex inactivation. Results show that animals acquired the reference memory task in the water maze, and the extinction task was successfully completed without significant impairment. However, analysis of the functional brain networks involved by cytochrome oxidase activity interregional correlations showed changes in brain networks between the group treated with Muscimol as compared to the saline-treated group, supporting the involvement of the mammillary bodies at a the late stage in the memory extinction process. Copyright © 2015 Elsevier B.V. All rights reserved.

Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

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Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

2012-11-01

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

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Aznar, Susana; Klein, Anders B

2013-12-01

The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

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

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia.

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Holi, Matti M; Eronen, Markku; Toivonen, Kari; Toivonen, Päivi; Marttunen, Mauri; Naukkarinen, Hannu

2004-01-01

In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.

Hyper-connectivity and hyper-plasticity in the medial prefrontal cortex in the valproic Acid animal model of autism

DEFF Research Database (Denmark)

Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

2008-01-01

of synapses. The microcircuit alterations found in the prefrontal cortex are therefore similar to the alterations previously found in the somatosensory cortex. Hyper-connectivity and hyper-plasticity in the prefrontal cortex implies hyper-functionality of one of the highest order processing regions...

The role of the prefrontal cortex in controlling gender-stereotypical associations: a TMS investigation.

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Cattaneo, Zaira; Mattavelli, Giulia; Platania, Elisa; Papagno, Costanza

2011-06-01

Stereotypes associated with gender, race, ethnicity and religion are powerful forces in human social interactions. Previous neuroimaging and neuropsychological studies point to a role of the prefrontal cortex in controlling stereotypical responses. Here we used transcranial magnetic stimulation (TMS) in combination with an Implicit Association Test (IAT) to highlight the possible causal role of the left dorsolateral prefrontal cortex (DLPFC) and the right anterior dorsomedial prefrontal cortex (aDMPFC) in controlling gender-stereotypical responses. Young male and female participants were tested. Our results showed that applying TMS over the left DLPFC and the right aDMPFC increased the gender-stereotypical bias in male participants compared to when TMS was applied to a control site (vertex). This suggests that both the left DLPFC and the right aDMPFC play a direct role in stereotyping. Females did not show a significant gender bias on the IAT; correspondingly their responses were unaffected by TMS. Copyright © 2011 Elsevier Inc. All rights reserved.

Online effects of transcranial direct current stimulation on prefrontal metabolites in gambling disorder.

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Dickler, Maya; Lenglos, Christophe; Renauld, Emmanuelle; Ferland, Francine; Edden, Richard A; Leblond, Jean; Fecteau, Shirley

2018-03-15

Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prefrontal Cortex Networks Shift from External to Internal Modes during Learning

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Brincat, Scott L.

2016-01-01

As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with “internal” memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)—regions critical for sensory associations—of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11–27 Hz) oscillatory power and synchrony associated with “top-down” or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing. SIGNIFICANCE STATEMENT As we learn about items in our environment, their representations in our brain become increasingly enriched with our acquired “top-down” knowledge. We found that in the prefrontal cortex, but not the hippocampus, processing of external sensory inputs decreased while internal network dynamics related to top-down processing increased. The results suggest that during learning, prefrontal cortex networks shift their resources from external (sensory) to internal (memory) processing. PMID:27629722

Association between prefrontal N-acetylaspartate and insight in psychotic disorders

NARCIS (Netherlands)

Larabi, Daouia I.; Liemburg, Edith; Pijnenborg, Gerdina H.M. Pijnenborg; Sibeijn-Kuiper, Anita; de Vos, Annerieke E.; Bais, Leonie; Knegtering, Henderikus; Curcic-Blake, Branisalava; Aleman, Andre

Insight is impaired in most patients with psychosis and has been associated with poorer prognosis. The exact neural basis of impaired insight is still unknown, but it may involve disrupted prefrontal neural connectivity. Numerous studies have indeed found white matter (WM) abnormalities in

Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

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McCarthy, Deirdre M; Bhide, Pradeep G

2012-01-01

Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects. Copyright © 2012 S. Karger AG, Basel.

Semantic encoding and retrieval in the left inferior prefrontal cortex: a functional MRI study of task difficulty and process specificity.

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Demb, J B; Desmond, J E; Wagner, A D; Vaidya, C J; Glover, G H; Gabrieli, J D

1995-09-01

Prefrontal cortical function was examined during semantic encoding and repetition priming using functional magnetic resonance imaging (fMRI), a noninvasive technique for localizing regional changes in blood oxygenation, a correlate of neural activity. Words studied in a semantic (deep) encoding condition were better remembered than words studied in both easier and more difficult nonsemantic (shallow) encoding conditions, with difficulty indexed by response time. The left inferior prefrontal cortex (LIPC) (Brodmann's areas 45, 46, 47) showed increased activation during semantic encoding relative to nonsemantic encoding regardless of the relative difficulty of the nonsemantic encoding task. Therefore, LIPC activation appears to be related to semantic encoding and not task difficulty. Semantic encoding decisions are performed faster the second time words are presented. This represents semantic repetition priming, a facilitation in semantic processing for previously encoded words that is not dependent on intentional recollection. The same LIPC area activated during semantic encoding showed decreased activation during repeated semantic encoding relative to initial semantic encoding of the same words. This decrease in activation during repeated encoding was process specific; it occurred when words were semantically reprocessed but not when words were nonsemantically reprocessed. The results were apparent in both individual and averaged functional maps. These findings suggest that the LIPC is part of a semantic executive system that contributes to the on-line retrieval of semantic information.

Single unit activity in the medial prefrontal cortex during Pavlovian heart rate conditioning: Effects of peripheral autonomic blockade.

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Powell, D A; Ginsberg, Jay P

2005-11-01

Electrical activity was recorded from single neurons in the medial prefrontal cortex of rabbits during differential Pavlovian heart rate (HR) conditioning. A heterogeneous population of cells were found, some of which showed CS-evoked increases and others CS-evoked decreases in discharge, while some cells were biphasic. A subset of cells also showed trial-related changes in discharge that were related to acquisition of the HR discrimination between the reinforced CS+ and non-reinforced CS-. Administration of the peripheral cholinergic antagonist, methylscopolamine, and the andrenergic antagonist, atenolol, either increased or decreased maintained baseline activity of many cells, but had little or no effect on the CS-evoked activity of these cells. Waveform changes also did not result from administration of these drugs. This finding suggests that CS-evoked mPFC activity is not being driven by cardiac afferent input to CNS cardiac control centers. Previous studies have shown that ibotenic acid lesions of this area greatly decreases the magnitude of decelerative heart rate conditioned responses; the latter finding, plus the results of the present study, suggest that processing of CS/US contingencies by the prefrontal cortex contributes to the acquisition of autonomic changes during Pavlovian conditioning.

Electrophysiological mapping of novel prefrontal - cerebellar pathways

Directory of Open Access Journals (Sweden)

Thomas C Watson

2009-08-01

Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

Right ventrolateral prefrontal cortex mediates individual differences in conflict-driven cognitive control

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Egner, Tobias

2013-01-01

Conflict adaptation – a conflict-triggered improvement in the resolution of conflicting stimulus or response representations – has become a widely used probe of cognitive control processes in both healthy and clinical populations. Previous functional magnetic resonance imaging (fMRI) studies have localized activation foci associated with conflict resolution to dorsolateral prefrontal cortex (dlPFC). The traditional group-analysis approach employed in these studies highlights regions that are, on average, activated during conflict resolution, but does not necessarily reveal areas mediating individual differences in conflict resolution, because between-subject variance is treated as noise. Here, we employed a complementary approach in order to elucidate the neural bases of variability in the proficiency of conflict-driven cognitive control. We analyzed two independent fMRI data sets of face-word Stroop tasks by using individual variability in the behavioral expression of conflict adaptation as the metric against which brain activation was regressed, while controlling for individual differences in mean reaction time and Stroop interference. Across the two experiments, a replicable neural substrate of individual variation in conflict adaptation was found in ventrolateral prefrontal cortex (vlPFC), specifically, in the right inferior frontal gyrus, pars orbitalis (BA 47). Unbiased regression estimates showed that variability in activity in this region accounted for ~40% of the variance in behavioral expression of conflict adaptation across subjects, thus documenting a heretofore unsuspected key role for vlPFC in mediating conflict-driven adjustments in cognitive control. We speculate that vlPFC plays a primary role in conflict control that is supplemented by dlPFC recruitment under conditions of suboptimal performance. PMID:21568631

Benefit of the doubt: a new view of the role of the prefrontal cortex in executive functioning and decision making

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Erik William Asp

2013-05-01

Full Text Available 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

Common and dissociable prefrontal loci associated with component mechanisms of analogical reasoning.

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Cho, Soohyun; Moody, Teena D; Fernandino, Leonardo; Mumford, Jeanette A; Poldrack, Russell A; Cannon, Tyrone D; Knowlton, Barbara J; Holyoak, Keith J

2010-03-01

The ability to draw analogies requires 2 key cognitive processes, relational integration and resolution of interference. The present study aimed to identify the neural correlates of both component processes of analogical reasoning within a single, nonverbal analogy task using event-related functional magnetic resonance imaging. Participants verified whether a visual analogy was true by considering either 1 or 3 relational dimensions. On half of the trials, there was an additional need to resolve interference in order to make a correct judgment. Increase in the number of dimensions to integrate was associated with increased activation in the lateral prefrontal cortex as well as lateral frontal pole in both hemispheres. When there was a need to resolve interference during reasoning, activation increased in the lateral prefrontal cortex but not in the frontal pole. We identified regions in the middle and inferior frontal gyri which were exclusively sensitive to demands on each component process, in addition to a partial overlap between these neural correlates of each component process. These results indicate that analogical reasoning is mediated by the coordination of multiple regions of the prefrontal cortex, of which some are sensitive to demands on only one of these 2 component processes, whereas others are sensitive to both.

Ventromedial prefrontal cortex, adding value to autobiographical memories

OpenAIRE

Lin, W. J.; Horner, A. J.; Burgess, N.

2016-01-01

The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found tha...

Higher Order Spike Synchrony in Prefrontal Cortex during visual memory

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Gordon ePipa

2011-06-01

Full Text Available Precise temporal synchrony of spike firing has been postulated as an important neuronal mechanism for signal integration and the induction of plasticity in neocortex. As prefrontal cortex plays an important role in organizing memory and executive functions, the convergence of multiple visual pathways onto PFC predicts that neurons should preferentially synchronize their spiking when stimulus information is processed. Furthermore, synchronous spike firing should intensify if memory processes require the induction of neuronal plasticity, even if this is only for short-term. Here we show with multiple simultaneously recorded units in ventral prefrontal cortex that neurons participate in 3 ms precise synchronous discharges distributed across multiple sites separated by at least 500 µm. The frequency of synchronous firing is modulated by behavioral performance and is specific for the memorized visual stimuli. In particular, during the memory period in which activity is not stimulus driven, larger groups of up to 7 sites exhibit performance dependent modulation of their spike synchronization.

Using imaging to target the prefrontal cortex for transcranial magnetic stimulation studies in treatment-resistant depression

OpenAIRE

Johnson, Kevin A.; Ramsey, Dave; Kozel, Frank A.; Bohning, Daryl E.; Anderson, Berry; Nahas, Ziad; Sacke?m, Harold A.; George, Mark S.

2006-01-01

Structural imaging studies of the brains of patients with treatment-resistant depression (TRD) have found several abnormalities, including smaller hippocampus, orbitofrontal cortex, or pre?frontal cortex. Transcranial magnetic stimulation (TMS) is a noninvasive means of modulating brain activity, and has shown antidepressant treatment efficacy. 1 The initial methods used for targeting the prefrontal cortex are most likely insufficient. Herwig et al found that a common rule-based approach (the...

Prefrontal Dopamine in Associative Learning and Memory

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Puig, M. Victoria; Antzoulatos, Evan G.; Miller, Earl K.

2014-01-01

Learning to associate specific objects or actions with rewards and remembering the associations are everyday tasks crucial for our flexible adaptation to the environment. These higher-order cognitive processes depend on the prefrontal cortex (PFC) and frontostriatal circuits that connect areas in the frontal lobe with the striatum in the basal ganglia. Both structures are densely innervated by dopamine (DA) afferents that originate in the midbrain. Although the activity of DA neurons is thought to be important for learning, the exact role of DA transmission in frontostriatal circuits during learning-related tasks is still unresolved. Moreover, the neural substrates of this modulation are poorly understood. Here, we review our recent work in monkeys utilizing local pharmacology of DA agents in the PFC to investigate the cellular mechanisms of DA modulation of associative learning and memory. We show that blocking both D1 and D2 receptors in the lateral PFC impairs learning of new stimulus-response associations and cognitive flexibility, but not the memory of highly familiar associations. In addition, D2 receptors may also contribute to motivation. The learning deficits correlated with reductions of neural information about the associations in PFC neurons, alterations in global excitability and spike synchronization, and exaggerated alpha and beta neural oscillations. Our findings provide new insights into how DA transmission modulate associative learning and memory processes in frontostriatal systems. PMID:25241063

Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

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Rebecca M Shansky

2013-04-01

Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

khat distorts the prefrontal cortex histology and function of adult

African Journals Online (AJOL)

2018-02-28

Feb 28, 2018 ... It affects many brain centers including the prefrontal cortex which is the ... cognitive behaviors however; it is linked to many psychological ... by traumatic events while others experience ... scientific research in exposing the effects. ... between 3 to 5pm daily. ... needle attached a plastic tubing was connected.

Measurements of the frontal and prefrontal lobe volumes by three dimensional magnetic resonance imaging scan. III. Analysis of sex differences with advanced age

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Kanemura, Hideaki; Aihara, Masao; Nakazawa, Shinpei [Yamanashi Medical Univ., Tamaho (Japan)

2002-09-01

To determine whether there is sex difference in the growth of the frontal and prefrontal lobes, we quantitatively measured the volume of these lobes by three dimensional (3-D) MRI in healthy 12 males (5 months to 39 years) and six females (1 year 11 months to 27 years). The left and right lobes were studied separately. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5 T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. In males, the left to right ratio (L/R ratio) of the frontal and prefrontal lobes increased with age. On the contrary, in females, L/R ratio of the frontal and prefrontal lobes showed no significant change with advancing age. These results highlighted sex-specific maturational changes of the frontal and prefrontal lobes and suggested that quantitative data on the frontal and prefrontal lobe are important in interpreting brain abnormalities in children with developmental disorders. (author)

Measurements of the frontal and prefrontal lobe volumes by three dimensional magnetic resonance imaging scan. III. Analysis of sex differences with advanced age

International Nuclear Information System (INIS)

Kanemura, Hideaki; Aihara, Masao; Nakazawa, Shinpei

2002-01-01

To determine whether there is sex difference in the growth of the frontal and prefrontal lobes, we quantitatively measured the volume of these lobes by three dimensional (3-D) MRI in healthy 12 males (5 months to 39 years) and six females (1 year 11 months to 27 years). The left and right lobes were studied separately. The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5 T MR imager. The frontal and prefrontal lobe volumes were measured by the volume measurement function of the Workstation. In males, the left to right ratio (L/R ratio) of the frontal and prefrontal lobes increased with age. On the contrary, in females, L/R ratio of the frontal and prefrontal lobes showed no significant change with advancing age. These results highlighted sex-specific maturational changes of the frontal and prefrontal lobes and suggested that quantitative data on the frontal and prefrontal lobe are important in interpreting brain abnormalities in children with developmental disorders. (author)

Molecular correlates of impaired prefrontal plasticity in response to chronic stress

NARCIS (Netherlands)

Kuipers, SD; Trentani, A; Den Boer, JA; Ter Horst, GJ

Disturbed adaptations at the molecular and cellular levels following stress could represent compromised neural plasticity that contributes to the pathophysiology of stress-induced disorders. Evidence illustrates atrophy and cell death of stress-vulnerable neurones in the prefrontal cortex. Reduced

Reciprocal neural response within lateral and ventral medial prefrontal cortex during hot and cold reasoning.

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Goel, Vinod; Dolan, Raymond J

2003-12-01

Logic is widely considered the basis of rationality. Logical choices, however, are often influenced by emotional responses, sometimes to our detriment, sometimes to our advantage. To understand the neural basis of emotionally neutral ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using event-related fMRI, as they made logical judgments about arguments that varied in emotional saliency. Despite identical logical form and content categories across "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal cortex showed reciprocal response patterns as a function of emotional saliency of content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in enhanced activation in VMPFC and suppression of activation in L/DLPFC. This reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural system for reasoning, the configuration of which is strongly influenced by emotional saliency.

Age-modulated association between prefrontal NAA and the BDNF gene.

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Salehi, Basira; Preuss, Nora; van der Veen, Jan Willem; Shen, Jun; Neumeister, Alexander; Drevets, Wayne C; Hodgkinson, Colin; Goldman, David; Wendland, Jens R; Singleton, Andrew; Gibbs, Jesse R; Cookson, Mark R; Hasler, Gregor

2013-07-01

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p = 0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 × age interaction on NAA level (p = 0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17 yr. NAA level decreased with advancing age for genotype TT (p = 0.001) but not for genotype CT (p = 0.82) or CC (p = 0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.

A portable, multi-channel fNIRS system for prefrontal cortex: Preliminary study on neurofeedback and imagery tasks (Conference Presentation)

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Paik, Seung-ho; Kim, Beop-Min

2016-03-01

fNIRS is a neuroimaging technique which uses near-infrared light source in the 700-1000 nm range and enables to detect hemodynamic changes (i.e., oxygenated hemoglobin, deoxygenated hemoglobin, blood volume) as a response to various brain processes. In this study, we developed a new, portable, prefrontal fNIRS system which has 12 light sources, 15 detectors and 108 channels with a sampling rate of 2 Hz. The wavelengths of light source are 780nm and 850nm. ATxmega128A1, 8bit of Micro controller unit (MCU) with 200~4095 resolution along with MatLab data acquisition algorithm was utilized. We performed a simple left and right finger movement imagery tasks which produced statistically significant changes of oxyhemoglobin concentrations in the dorsolateral prefrontal cortex (dlPFC) areas. We observed that the accuracy of the imagery tasks can be improved by carrying out neurofeedback training, during which a real-time feedback signal is provided to a participating subject. The effects of the neurofeedback training was later visually verified using the 3D NIRfast imaging. Our portable fNIRS system may be useful in non-constraint environment for various clinical diagnoses.

The topology of connections between rat prefrontal and temporal cortices

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Stacey eBedwell

2015-05-01

Full Text Available Understanding the structural organisation of the prefrontal cortex (PFC is an important step towards determining its functional organisation. Here we investigated the organisation of PFC using different neuronal tracers. We injected retrograde (Fluoro-Gold, 100nl and anterograde (Biotinylated dextran amine (BDA or Fluoro-Ruby, 100nl tracers into sites within PFC subdivisions (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital along a coronal axis within PFC. At each injection site one injection was made of the anterograde tracer and one injection was made of the retrograde tracer. The projection locations of retrogradely labelled neurons and anterogradely labelled axon terminals were then analysed in the temporal cortex: area Te, entorhinal and perirhinal cortex. We found evidence for an ordering of both the anterograde (anterior-posterior, dorsal-ventral and medial-lateral axes: p<0.001 and retrograde (anterior-posterior, dorsal-ventral and medial-lateral axes: p<0.001 connections of PFC. We observed that anterograde and retrograde labelling in ipsilateral temporal cortex (i.e. PFC inputs and outputs often occurred reciprocally (i.e. the same brain region, such as area 35d in perirhinal cortex, contained anterograde and retrograde labelling. However, often the same specific columnar temporal cortex regions contained only either labelling of retrograde or anterograde tracer, indicating that PFC inputs and outputs are frequently non-matched.

Minocycline restores cognitive-relative altered proteins in young bile duct-ligated rat prefrontal cortex.

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Li, Shih-Wen; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Hsu, Mei-Hsin; Tain, You-Lin; Chang, Kow-Aung; Huang, Li-Tung

2017-07-01

Bile duct ligation (BDL) model is used to study hepatic encephalopathy accompanied by cognitive impairment. We employed the proteomic analysis approach to evaluate cognition-related proteins in the prefrontal cortex of young BDL rats and analyzed the effect of minocycline on these proteins and spatial memory. BDL was induced in young rats at postnatal day 17. Minocycline as a slow-release pellet was implanted into the peritoneum. Morris water maze test and two-dimensional liquid chromatography-tandem mass spectrometry were used to evaluate spatial memory and prefrontal cortex protein expression, respectively. We used 2D/LC-MS/MS to analyze for affected proteins in the prefrontal cortex of young BDL rats. Results were verified with Western blotting, immunohistochemistry, and quantitative real-time PCR. The effect of minocycline in BDL rats was assessed. BDL induced spatial deficits, while minocycline rescued it. Collapsin response mediator protein 2 (CRMP2) and manganese-dependent superoxide dismutase (MnSOD) were upregulated and nucleoside diphosphate kinase B (NME2) was downregulated in young BDL rats. BDL rats exhibited decreased levels of brain-derived neurotrophic factor (BDNF) mRNA as compared with those by the control. However, minocycline treatment restored CRMP2 and NME2 protein expression, BDNF mRNA level, and MnSOD activity to control levels. We demonstrated that BDL altered the expression of CRMP2, NME2, MnSOD, and BDNF in the prefrontal cortex of young BDL rats. However, minocycline treatment restored the expression of the affected mediators that are implicated in cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Advantages and disadvantages of intraoperative language tasks in awake surgery: a three-task approach for prefrontal tumors.

Science.gov (United States)

Rofes, A; Spena, G; Miozzo, A; Fontanella, M M; Miceli, G

2015-12-01

Multidisciplinary efforts are being made to provide surgical teams with sensitive and specific tasks for language mapping in awake surgery. Researchers and clinicians have elaborated different tasks over time. A fair amount of work has been directed to study the neurofunctional correlates of some of these tasks, and there is recent interest in their standardization. However, little discussion exists on the advantages and disadvantages that each task poses from the perspective of the cognitive neuroscience of language. Such an approach may be a relevant step to assess task validity, to avoid using tasks that tap onto similar processes, and to provide patients with a surgical treatment that ensures maximal tumor resection while avoiding postoperative language deficits. An understanding of the language components that each task entails may also be relevant to improve the current assessments and the ways in which tasks are administered, and to disentangle neurofunctional questions. We reviewed 17 language mapping tasks that have been used in awake surgery. Overt production tasks have been a preferred choice over comprehension tasks. Tasks tapping lexico-semantic processes, particularly object-naming, maintain their role as gold standards. Automated speech tasks are used to detect speech errors and to set the amplitude of the stimulator. Comprehension tasks, reading and writing tasks, and tasks that assess grammatical aspects of language may be regularly administered in the near future. We provide examples of a three-task approach we are administering to patients with prefrontal lesions. We believe that future advances in this area are contingent upon reviewing gold standards and introducing new assessment tools.

An exploratory study of the effects of spatial working-memory load on prefrontal activation in low- and high-performing elderly.

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Vermeij, Anouk; van Beek, Arenda H E A; Reijs, Babette L R; Claassen, Jurgen A H R; Kessels, Roy P C

2014-01-01

Older adults show more bilateral prefrontal activation during cognitive performance than younger adults, who typically show unilateral activation. This over-recruitment has been interpreted as compensation for declining structure and function of the brain. Here we examined how the relationship between behavioral performance and prefrontal activation is modulated by different levels of working-memory load. Eighteen healthy older adults (70.8 ± 5.0 years; MMSE 29.3 ± 0.9) performed a spatial working-memory task (n-back). Oxygenated ([O2Hb]) and deoxygenated ([HHb]) hemoglobin concentration changes were registered by two functional Near-Infrared Spectroscopy (fNIRS) channels located over the left and right prefrontal cortex. Increased working-memory load resulted in worse performance compared to the control condition. [O2Hb] increased with rising working-memory load in both fNIRS channels. Based on the performance in the high working-memory load condition, the group was divided into low and high performers. A significant interaction effect of performance level and hemisphere on [O2Hb] increase was found, indicating that high performers were better able to keep the right prefrontal cortex engaged under high cognitive demand. Furthermore, in the low performers group, individuals with a larger decline in task performance from the control to the high working-memory load condition had a larger bilateral increase of [O2Hb]. The high performers did not show a correlation between performance decline and working-memory load related prefrontal activation changes. Thus, additional bilateral prefrontal activation in low performers did not necessarily result in better cognitive performance. Our study showed that bilateral prefrontal activation may not always be successfully compensatory. Individual behavioral performance should be taken into account to be able to distinguish successful and unsuccessful compensation or declined neural efficiency.

Attention, emotion, and deactivation of default activity in inferior medial prefrontal cortex

DEFF Research Database (Denmark)

Geday, Jacob; Gjedde, Albert

2008-01-01

Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC...... with positron emission tomography (PET) of labeled water (H(15)2O) uptake in brain of 14 healthy subjects. The subjects performed either a less demanding or a more demanding task of attention while they watched neutral and emotive images of people in realistic indoor or outdoor situations. In the less demanding...... cortices, revealed significant activation in the fusiform gyrus, independently of the task. In contrast, we found no effect of emotional content in the IMPC, where emotions failed to override the effect of the task. The results are consistent with a role of the IMPC in the selection among competitive...

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

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Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

2018-01-01

to form the anatomical basis for the impaired functioning of this brain area. Indeed, impaired functioning of the prefrontal cortex, such as cognitive deficits are common in stressed individuals as well as in depressed patients. PMID:29440995

Reduced Synapse and Axon Numbers in the Prefrontal Cortex of Rats Subjected to a Chronic Stress Model for Depression

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Dávid Csabai

2018-01-01

connectivity is likely to form the anatomical basis for the impaired functioning of this brain area. Indeed, impaired functioning of the prefrontal cortex, such as cognitive deficits are common in stressed individuals as well as in depressed patients.

Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders.

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Shepard, Ryan; Page, Chloe E; Coutellier, Laurence

2016-09-22

Stress-induced modifications of the prefrontal cortex (PFC) are believed to contribute to the onset of mood disorders, such as depression and anxiety, which are more prevalent in women. In depression, the PFC is hypoactive; however the origin of this hypoactivity remains unclear. Possibly, stress could impact the prefrontal GABAergic inhibitory system that, as a result, impairs the functioning of downstream limbic structures controlling emotions. Preclinical evidence indicates that the female PFC is more sensitive to the effects of stress. These findings suggest that exposure to stress could lead to sex-specific alterations in prefrontal GABAergic signaling, which contribute to sex-specific abnormal functioning of limbic regions. These limbic changes could promote the onset of depressive and anxiety behaviors in a sex-specific manner, providing a possible mechanism mediating sex differences in the clinical presentation of stress-related mood disorders. We addressed this hypothesis using a mouse model of stress-induced depressive-like behaviors: the unpredictable chronic mild stress (UCMS) paradigm. We observed changes in prefrontal GABAergic signaling after exposure to UCMS most predominantly in females. Increased parvalbumin (PV) expression and decreased prefrontal neuronal activity were correlated in females with severe emotionality deficit following UCMS, and with altered activity of the amygdala. In males, small changes in emotionality following UCMS were associated with minor changes in prefrontal PV expression, and with hypoactivity of the nucleus accumbens. Our data suggest that prefrontal hypoactivity observed in stress-related mood disorders could result from stress-induced increases in PV expression, particularly in females. This increased vulnerability of the female prefrontal PV system to stress could underlie sex differences in the prevalence and symptomatology of stress-related mood disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All

Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.

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van der Schaaf, Marieke E; De Lange, Floris P; Schmits, Iris C; Geurts, Dirk E M; Roelofs, Karin; van der Meer, Jos W M; Toni, Ivan; Knoop, Hans

2017-02-15

Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity). We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls. The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups. CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment

NARCIS (Netherlands)

van Harmelen, A.L.; van Tol, M.J.; Dalgleish, T.; van der Wee, N.J.A.; Veltman, D.J.; Aleman, A.; Spinhoven, P.; Penninx, B.W.J.H.; Elzinga, B.M.

2014-01-01

Childhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional

Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS

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Yukifumi Monden

2015-01-01

Full Text Available While a growing body of neurocognitive research has explored the neural substrates associated with attention deficit hyperactive disorder (ADHD, an objective biomarker for diagnosis has not been established. The advent of functional near-infrared spectroscopy (fNIRS, which is a noninvasive and unrestrictive method of functional neuroimaging, raised the possibility of introducing functional neuroimaging diagnosis in young ADHD children. Previously, our fNIRS-based measurements successfully visualized the hypoactivation pattern in the right prefrontal cortex during a go/no-go task in ADHD children compared with typically developing control children at a group level. The current study aimed to explore a method of individual differentiation between ADHD and typically developing control children using multichannel fNIRS, emphasizing how spatial distribution and amplitude of hemodynamic response are associated with inhibition-related right prefrontal dysfunction. Thirty ADHD and thirty typically developing control children underwent a go/no-go task, and their cortical hemodynamics were assessed using fNIRS. We explored specific regions of interest (ROIs and cut-off amplitudes for cortical activation to distinguish ADHD children from control children. The ROI located on the border of inferior and middle frontal gyri yielded the most accurate discrimination. Furthermore, we adapted well-formed formulae for the constituent channels of the optimized ROI, leading to improved classification accuracy with an area under the curve value of 85% and with 90% sensitivity. Thus, the right prefrontal hypoactivation assessed by fNIRS would serve as a potentially effective biomarker for classifying ADHD children at the individual level.

Top-Down Control of Visual Attention by the Prefrontal Cortex. Functional Specialization and Long-Range Interactions

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Paneri, Sofia; Gregoriou, Georgia G.

2017-01-01

The ability to select information that is relevant to current behavioral goals is the hallmark of voluntary attention and an essential part of our cognition. Attention tasks are a prime example to study at the neuronal level, how task related information can be selectively processed in the brain while irrelevant information is filtered out. Whereas, numerous studies have focused on elucidating the mechanisms of visual attention at the single neuron and population level in the visual cortices, considerably less work has been devoted to deciphering the distinct contribution of higher-order brain areas, which are known to be critical for the employment of attention. Among these areas, the prefrontal cortex (PFC) has long been considered a source of top-down signals that bias selection in early visual areas in favor of the attended features. Here, we review recent experimental data that support the role of PFC in attention. We examine the existing evidence for functional specialization within PFC and we discuss how long-range interactions between PFC subregions and posterior visual areas may be implemented in the brain and contribute to the attentional modulation of different measures of neural activity in visual cortices. PMID:29033784

Top-Down Control of Visual Attention by the Prefrontal Cortex. Functional Specialization and Long-Range Interactions

Directory of Open Access Journals (Sweden)

Sofia Paneri

2017-09-01

Full Text Available The ability to select information that is relevant to current behavioral goals is the hallmark of voluntary attention and an essential part of our cognition. Attention tasks are a prime example to study at the neuronal level, how task related information can be selectively processed in the brain while irrelevant information is filtered out. Whereas, numerous studies have focused on elucidating the mechanisms of visual attention at the single neuron and population level in the visual cortices, considerably less work has been devoted to deciphering the distinct contribution of higher-order brain areas, which are known to be critical for the employment of attention. Among these areas, the prefrontal cortex (PFC has long been considered a source of top-down signals that bias selection in early visual areas in favor of the attended features. Here, we review recent experimental data that support the role of PFC in attention. We examine the existing evidence for functional specialization within PFC and we discuss how long-range interactions between PFC subregions and posterior visual areas may be implemented in the brain and contribute to the attentional modulation of different measures of neural activity in visual cortices.

Extrapunitive and intropunitive individuals activate different parts of the prefrontal cortex under an ego-blocking frustration.

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Minamoto, Takehiro; Osaka, Mariko; Yaoi, Ken; Osaka, Naoyuki

2014-01-01

Different people make different responses when they face a frustrating situation: some punish others (extrapunitive), while others punish themselves (intropunitive). Few studies have investigated the neural structures that differentiate extrapunitive and intropunitive individuals. The present fMRI study explored these neural structures using two different frustrating situations: an ego-blocking situation which blocks a desire or goal, and a superego-blocking situation which blocks self-esteem. In the ego-blocking condition, the extrapunitive group (n = 9) showed greater activation in the bilateral ventrolateral prefrontal cortex, indicating that these individuals prefer emotional processing. On the other hand, the intropunitive group (n = 9) showed greater activation in the left dorsolateral prefrontal cortex, possibly reflecting an effortful control for anger reduction. Such patterns were not observed in the superego-blocking condition. These results indicate that the prefrontal cortex is the source of individual differences in aggression direction in the ego-blocking situation.

Predicting Treatment Outcomes from Prefrontal Cortex Activation for Self-Harming Patients with Borderline Personality Disorder: A Preliminary Study

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Anthony Charles Ruocco

2016-05-01

Full Text Available Self-harm is a potentially lethal symptom of borderline personality disorder (BPD that often improves with dialectical behavior therapy (DBT. While DBT is effective for reducing self-harm in many patients with BPD, a small but significant number of patients either does not improve in treatment or ends treatment prematurely. Accordingly, it is crucial to identify factors that may prospectively predict which patients are most likely to benefit from and remain in treatment. In the present preliminary study, twenty-nine actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex during impulse control prior to beginning DBT and after seven months of treatment. Patients that reduced their frequency of self-harm the most over treatment displayed lower levels of neural activation in the bilateral dorsolateral prefrontal cortex prior to beginning treatment, and they showed the greatest increases in activity within this region after seven months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial prefrontal cortex and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right dorsolateral prefrontal cortex even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the prefrontal cortex underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT.

Association between catechol-O-methyltrasferase Val108/158Met genotype and prefrontal hemodynamic response in schizophrenia.

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Ryu Takizawa

Full Text Available BACKGROUND: "Imaging genetics" studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS. METHODOLOGY/PRINCIPAL FINDINGS: Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls. CONCLUSIONS/SIGNIFICANCE: These data suggest that the prefrontal NIRS signals can noninvasively detect the impact

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

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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.

Positive and Negative Affect and Adolescent Adjustment: Moderation Effects of Prefrontal Functioning.

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Brieant, Alexis; Holmes, Christopher J; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

2018-03-01

We examined whether cognitive control moderates the effects of emotion on adolescent internalizing and externalizing symptomatology in a longitudinal study of 138 adolescents. Self-reported positive affect (PA) and negative affect and behavioral and neural indicators of cognitive control, indexed by performance and prefrontal hemodynamic response during a cognitive interference task, were collected at Time 1. Self-reported internalizing and externalizing symptomatology were collected at Time 1 and Time 2 (1 year later). Results indicated that higher PA predicted decreases in externalizing symptomatology, but only for adolescents with poor neural cognitive control. No moderation effects were found for behavioral cognitive control. Findings imply the beneficial effects of PA on the development of externalizing problems among adolescents with poor prefrontal functioning. © 2018 Society for Research on Adolescence.

Processing and Integration of Contextual Information in Monkey Ventrolateral Prefrontal Neurons during Selection and Execution of Goal-Directed Manipulative Actions.

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Bruni, Stefania; Giorgetti, Valentina; Bonini, Luca; Fogassi, Leonardo

2015-08-26

The prefrontal cortex (PFC) is deemed to underlie the complexity, flexibility, and goal-directedness of primates' behavior. Most neurophysiological studies performed so far investigated PFC functions with arm-reaching or oculomotor tasks, thus leaving unclear whether, and to which extent, PFC neurons also play a role in goal-directed manipulative actions, such as those commonly used by primates during most of their daily activities. Here we trained two macaques to perform or withhold grasp-to-eat and grasp-to-place actions, depending on the combination of two subsequently presented cues: an auditory go/no-go cue (high/low tone) and a visually presented target (food/object). By varying the order of presentation of the two cues, we could segment and independently evaluate the processing and integration of contextual information allowing the monkey to make a decision on whether or not to act, and what action to perform. We recorded 403 task-related neurons from the ventrolateral prefrontal cortex (VLPFC): unimodal sensory-driven (37%), motor-related (21%), unimodal sensory-and-motor (23%), and multisensory (19%) neurons. Target and go/no-go selectivity characterized most of the recorded neurons, particularly those endowed with motor-related discharge. Interestingly, multisensory neurons appeared to encode a behavioral decision independently from the sensory modality of the stimulus allowing the monkey to make it: some of them reflected the decision to act or refraining from acting (56%), whereas others (44%) encoded the decision to perform (or withhold) a specific action (e.g., grasp-to-eat). Our findings indicate that VLPFC neurons play a role in the processing of contextual information underlying motor decision during goal-directed manipulative actions. We demonstrated that macaque ventrolateral prefrontal cortex (VLPFC) neurons show remarkable selectivity for different aspects of the contextual information allowing the monkey to select and execute goal

Reward Inference by Primate Prefrontal and Striatal Neurons

OpenAIRE

Pan, Xiaochuan; Fan, Hongwei; Sawa, Kosuke; Tsuda, Ichiro; Tsukada, Minoru; Sakagami, Masamichi

2014-01-01

The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Im...

Brain activation during fast driving in a driving simulator: the role of the lateral prefrontal cortex.

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Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

2008-07-16

Little is currently known about the neural underpinnings of the cognitive control of driving behavior in realistic situations and of the driver's speeding behavior in particular. In this study, participants drove in realistic scenarios presented in a high-end driving simulator. Scalp-recorded EEG oscillations in the alpha-band (8-13 Hz) with a 30-electrode montage were recorded while the participants drove under different conditions: (i) excessively fast (Fast), (ii) in a controlled manner at a safe speed (Correct), and (iii) impatiently in the context of testing traffic conditions (Impatient). Intracerebral sources of alpha-band activation were estimated using low resolution electrical tomography. Given that previous studies have shown a strong negative correlation between the Bold response in the frontal cortex and the alpha-band power, we used alpha-band-related activity as an estimation of frontal activation. Statistical analysis revealed more alpha-band-related activity (i.e. less neuronal activation) in the right lateral prefrontal cortex, including the dorsolateral prefrontal cortex, during fast driving. Those participants who speeded most and exhibited greater risk-taking behavior demonstrated stronger alpha-related activity (i.e. less neuronal activation) in the left anterior lateral prefrontal cortex. These findings are discussed in the context of current theories about the role of the lateral prefrontal cortex in controlling risk-taking behavior, task switching, and multitasking.

Changes of heart rate variability and prefrontal oxygenation during Tai Chi practice versus arm ergometer cycling.

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Lu, Xi; Hui-Chan, Christina Wan-Ying; Tsang, William Wai-Nam

2016-11-01

[Purpose] Exercise has been shown to improve cardiovascular fitness and cognitive function. Whether the inclusion of mind over exercise would increase parasympathetic control of the heart and brain activities more than general exercise at a similar intensity is not known. The aim of this study was to compare the effects of Tai Chi (mind-body exercise) versus arm ergometer cycling (body-focused exercise) on the heart rate variability and prefrontal oxygenation level. [Subjects and Methods] A Tai Chi master was invited to perform Tai Chi and arm ergometer cycling with similar exercise intensity on two separate days. Heart rate variability and prefrontal oxyhemoglobin levels were measured continuously by a RR recorder and near-infrared spectroscopy, respectively. [Results] During Tai Chi exercise, spectral analysis of heart rate variability demonstrated a higher high-frequency power as well as a lower low-frequency/high-frequency ratio than during ergometer cycling, suggesting increased parasympathetic and decreased sympathetic control of the heart. Also, prefrontal oxyhemoglobin and total hemoglobin levels were higher than those during arm ergometer exercise. [Conclusion] These findings suggest that increased parasympathetic control of the heart and prefrontal activities may be associated with Tai Chi practice. Having a "mind" component in Tai Chi could be more beneficial for older adults' cardiac health and cognitive function than body-focused ergometer cycling.

The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant-induced dopamine release in the prefrontal cortex.

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Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Bini, Valentina; Gessa, Gian Luigi

2014-07-01

The dopamine-beta-hydroxylase inhibitor nepicastat has been shown to reproduce disulfiram ability to suppress the reinstatement of cocaine seeking after extinction in rats. To clarify its mechanism of action, we examined the effect of nepicastat, given alone or in association with cocaine or amphetamine, on catecholamine release in the medial prefrontal cortex and the nucleus accumbens, two key regions involved in the reinforcing and motivational effects of cocaine and in the reinstatement of cocaine seeking. Nepicastat effect on catecholamines was evaluated by microdialysis in freely moving rats. Nepicastat reduced noradrenaline release both in the medial prefrontal cortex and in the nucleus accumbens, and increased dopamine release in the medial prefrontal cortex but not in the nucleus accumbens. Moreover, nepicastat markedly potentiated cocaine- and amphetamine-induced extracellular dopamine accumulation in the medial prefrontal cortex but not in the nucleus accumbens. Extracellular dopamine accumulation produced by nepicastat alone or by its combination with cocaine or amphetamine was suppressed by the α2 -adrenoceptor agonist clonidine. It is suggested that nepicastat, by suppressing noradrenaline synthesis and release, eliminated the α2 -adrenoceptor mediated inhibitory mechanism that constrains dopamine release and cocaine- and amphetamine-induced dopamine release from noradrenaline or dopamine terminals in the medial prefrontal cortex. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

The Reduction of Ventrolateral Prefrontal Cortex Gray Matter Volume Correlates with Loss of Economic Rationality in Aging.

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Chung, Hui-Kuan; Tymula, Agnieszka; Glimcher, Paul

2017-12-06

The population of people above 65 years old continues to grow, and there is mounting evidence that as humans age they are more likely to make errors. However, the specific effect of neuroanatomical aging on the efficiency of economic decision-making is poorly understood. We used whole-brain voxel-based morphometry analysis to determine where reduction of gray matter volume in healthy female and male adults over the age of 65 years correlates with a classic measure of economic irrationality: violations of the Generalized Axiom of Revealed Preference. All participants were functionally normal with Mini-Mental State Examination scores ranging between 26 and 30. While our elders showed the previously reported decline in rationality compared with younger subjects, chronological age per se did not correlate with rationality measures within our population of elders. Instead, reduction of gray matter density in ventrolateral prefrontal cortex correlates tightly with irrational behavior. Interestingly, using a large fMRI sample and meta-analytic tool with Neurosynth, we found that this brain area shows strong coactivation patterns with nearly all of the value-associated regions identified in previous studies. These findings point toward a neuroanatomic locus for economic rationality in the aging brain and highlight the importance of understanding both anatomy and function in the study of aging, cognition, and decision-making. SIGNIFICANCE STATEMENT Age is a crucial factor in decision-making, with older individuals making more errors in choices. Using whole-brain voxel-based morphometry analysis, we found that reduction of gray matter density in ventrolateral prefrontal cortex correlates with economic irrationality: reduced gray matter volume in this area correlates with the frequency and severity of violations of the Generalized Axiom of Revealed Preference. Furthermore, this brain area strongly coactivates with other reward-associated regions identified with Neurosynth

The prefrontal cortex shows context-specific changes in effective connectivity to motor or visual cortex during the selection of action or colour

DEFF Research Database (Denmark)

Rowe, James B.; Stephan, Klaas E.; Friston, Karl

2005-01-01

The role of the prefrontal cortex remains controversial. Neuroimaging studies support modality-specific and process-specific functions related to working memory and attention. Its role may also be defined by changes in its influence over other brain regions including sensory and motor cortex. We...... used functional magnetic imaging (fMRI) to study the free selection of actions and colours. Control conditions used externally specified actions and colours. The prefrontal cortex was activated during free selection, regardless of modality, in contrast to modality-specific activations outside...... included high-order interactions between modality, selection and regional activity. There was greater coupling between prefrontal cortex and motor cortex during free selection and action tasks, and between prefrontal cortex and visual cortex during free selection of colours. The results suggest...

Absence of age-related prefrontal NAA change in adults with autism spectrum disorders.

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Aoki, Y; Abe, O; Yahata, N; Kuwabara, H; Natsubori, T; Iwashiro, N; Takano, Y; Inoue, H; Kawakubo, Y; Gonoi, W; Sasaki, H; Murakami, M; Katsura, M; Nippashi, Y; Takao, H; Kunimatsu, A; Matsuzaki, H; Tsuchiya, K J; Kato, N; Kasai, K; Yamasue, H

2012-10-23

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.

Prefrontal oxygenation correlates to the responses in facial skin blood flows during exposure to pleasantly charged movie.

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Matsukawa, Kanji; Endo, Kana; Asahara, Ryota; Yoshikawa, Miho; Kusunoki, Shinya; Ishida, Tomoko

2017-11-01

Our laboratory reported that facial skin blood flow may serve as a sensitive tool to assess an emotional status. Cerebral neural correlates during emotional interventions should be sought in relation to the changes in facial skin blood flow. To test the hypothesis that prefrontal activity has positive relation to the changes in facial skin blood flow during emotionally charged stimulation, we examined the dynamic changes in prefrontal oxygenation (with near-infrared spectroscopy) and facial skin blood flows (with two-dimensional laser speckle and Doppler flowmetry) during emotionally charged audiovisual challenges for 2 min (by viewing comedy, landscape, and horror movie) in 14 subjects. Hand skin blood flow and systemic hemodynamics were simultaneously measured. The extents of pleasantness and consciousness for each emotional stimulus were estimated by subjective rating from -5 (the most unpleasant; the most unconscious) to +5 (the most pleasant; the most conscious). Positively charged emotional stimulation (comedy) simultaneously decreased ( P  horror) or neutral (landscape) emotional stimulation did not alter or slightly decreased them. Any of hand skin blood flow and systemic cardiovascular variables did not change significantly during positively charged emotional stimulation. The changes in prefrontal oxygenation had a highly positive correlation with the changes in facial skin blood flow without altering perfusion pressure, and they were inversely correlated with the subjective rating of pleasantness. The reduction in prefrontal oxygenation during positively charged emotional stimulation suggests a decrease in prefrontal neural activity, which may in turn elicit neurally mediated vasoconstriction of facial skin blood vessels. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Stress-related methylation of the catechol-O-methyltransferase Val 158 allele predicts human prefrontal cognition and activity.

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Ursini, Gianluca; Bollati, Valentina; Fazio, Leonardo; Porcelli, Annamaria; Iacovelli, Luisa; Catalani, Assia; Sinibaldi, Lorenzo; Gelao, Barbara; Romano, Raffaella; Rampino, Antonio; Taurisano, Paolo; Mancini, Marina; Di Giorgio, Annabella; Popolizio, Teresa; Baccarelli, Andrea; De Blasi, Antonio; Blasi, Giuseppe; Bertolino, Alessandro

2011-05-04

DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory (WM), and it creates a CpG dinucleotide. We report that methylation of the Val(158) allele measured from peripheral blood mononuclear cells (PBMCs) of Val/Val humans is associated negatively with lifetime stress and positively with WM performance; it interacts with stress to modulate prefrontal activity during WM, such that greater stress and lower methylation are related to reduced cortical efficiency; and it is inversely related to mRNA expression and protein levels, potentially explaining the in vivo effects. Finally, methylation of COMT in prefrontal cortex and that in PBMCs of rats are correlated. The relationship of methylation of the COMT Val(158) allele with stress, gene expression, WM performance, and related brain activity suggests that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Moreover, these results demonstrate how stress-related DNA methylation of specific functional alleles impacts directly on human brain physiology beyond sequence variation.

The catechol-O-methyltransferase (COMT) Val158Met genotype modulates working memory-related dorsolateral prefrontal response and performance in bipolar disorder

DEFF Research Database (Denmark)

Miskowiak, K. W.; Kjærstad, H. L.; Støttrup, M. M.

2017-01-01

prefrontal cortex (dlPFC) (P=.016). Exploratory whole-brain analysis revealed a bilateral decrease in working memory-related dlPFC activity in the ValVal group vs the ValMet group which was not associated with differences in working memory performance during fMRI. Outside the MRI scanner, Val carriers...... performed worse in the CANTAB Spatial Working Memory task than Met homozygotes (P≤.006), with deficits being most pronounced in Val homozygotes. CONCLUSIONS: The association between Val allelic load, dlPFC activity and WM impairment points to a putative role of aberrant PFC dopamine tonus in the cognitive......-O-methyltransferase (COMT) gene is associated with reduced prefrontal cortex dopamine and exaggerated working memory-related prefrontal activity. This functional magnetic resonance imaging (fMRI) study investigated for the first time whether the COMT Val158Met genotype modulates prefrontal activity during spatial working...

tDCS of medial prefrontal cortex does not enhance interpersonal trust

NARCIS (Netherlands)

Colzato, L.S.; Sellaro, R.; van den Wildenberg, W.P.M.; Hommel, B.

2015-01-01

Interpersonal trust is an essential ingredient of many social relationships. Previous research has suggested that the medial Prefrontal Cortex (mPFC) may be a critical component in mediating the degree to which people trust others. Here we assessed the role of the mPFC in modulating interpersonal

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.

Extrapunitive and intropunitive individuals activate different parts of the prefrontal cortex under an ego-blocking frustration.

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Takehiro Minamoto

Full Text Available Different people make different responses when they face a frustrating situation: some punish others (extrapunitive, while others punish themselves (intropunitive. Few studies have investigated the neural structures that differentiate extrapunitive and intropunitive individuals. The present fMRI study explored these neural structures using two different frustrating situations: an ego-blocking situation which blocks a desire or goal, and a superego-blocking situation which blocks self-esteem. In the ego-blocking condition, the extrapunitive group (n = 9 showed greater activation in the bilateral ventrolateral prefrontal cortex, indicating that these individuals prefer emotional processing. On the other hand, the intropunitive group (n = 9 showed greater activation in the left dorsolateral prefrontal cortex, possibly reflecting an effortful control for anger reduction. Such patterns were not observed in the superego-blocking condition. These results indicate that the prefrontal cortex is the source of individual differences in aggression direction in the ego-blocking situation.

Converging models of schizophrenia - Network alterations of prefrontal cortex underlying cognitive impairments

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Sakurai, Takeshi; Gamo, Nao J; Hikida, Takatoshi; Kim, Sun-Hong; Murai, Toshiya; Tomoda, Toshifumi; Sawa, Akira

2015-01-01

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal. PMID:26408506

Functional connectivity of the ventral tegmental area and avolition in subjects with schizophrenia: a resting state functional MRI study.

Science.gov (United States)

Giordano, Giulia Maria; Stanziano, Mario; Papa, Michele; Mucci, Armida; Prinster, Anna; Soricelli, Andrea; Galderisi, Silvana

2018-04-10

Avolition, a deficit in goal-directed behavior, is a key aspect of negative symptoms. It is highly prevalent in schizophrenia and is associated to poor functional outcome and to measures of real life motivation, indicating that central to the concept is the lack of interest and motivation. In this study we tested the hypothesis that avolition is related to altered connectivity within dopaminergic cortico-striatal circuits involved in motivation processes. Since dopamine input to these circuits derives mostly from the ventro-tegmental area (VTA), we investigated the relationships between the resting-state functional connectivity (RS-FC) of the VTA and avolition in twenty-six subjects with schizophrenia (SCZ), treated with second-generation antipsychotics only, compared to twenty-two healthy controls (HC). SCZ, in comparison to HC, showed significantly reduced RS-FC of the VTA with bilateral ventro-lateral prefrontal cortex (VLPFC), bilateral insular cortex (IC) and right (R) lateral occipital complex (LOC) and increased RS-FC of the VTA with bilateral dorso-lateral prefrontal cortex (DLPFC). Significant negative correlations were found between avolition and RS-FC of the VTA with the bilateral IC, R VLPFC and R LOC. According to our findings, avolition is linked to a disconnectivity of the VTA from several key cortical regions involved in the integration of value information with action selection. These findings are in line with translational animal models of "auto-activation apathy". Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Prefrontal oxygenation correlates to the responses in facial skin blood flows during exposure to pleasantly charged movie

OpenAIRE

Matsukawa, Kanji; Endo, Kana; Asahara, Ryota; Yoshikawa, Miho; Kusunoki, Shinya; Ishida, Tomoko

2017-01-01

Abstract Our laboratory reported that facial skin blood flow may serve as a sensitive tool to assess an emotional status. Cerebral neural correlates during emotional interventions should be sought in relation to the changes in facial skin blood flow. To test the hypothesis that prefrontal activity has positive relation to the changes in facial skin blood flow during emotionally charged stimulation, we examined the dynamic changes in prefrontal oxygenation (with near‐infrared spectroscopy) and...

Prefrontal dopamine in associative learning and memory.

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Puig, M V; Antzoulatos, E G; Miller, E K

2014-12-12

Learning to associate specific objects or actions with rewards and remembering the associations are everyday tasks crucial for our flexible adaptation to the environment. These higher-order cognitive processes depend on the prefrontal cortex (PFC) and frontostriatal circuits that connect areas in the frontal lobe with the striatum in the basal ganglia. Both structures are densely innervated by dopamine (DA) afferents that originate in the midbrain. Although the activity of DA neurons is thought to be important for learning, the exact role of DA transmission in frontostriatal circuits during learning-related tasks is still unresolved. Moreover, the neural substrates of this modulation are poorly understood. Here, we review our recent work in monkeys utilizing local pharmacology of DA agents in the PFC to investigate the cellular mechanisms of DA modulation of associative learning and memory. We show that blocking both D1 and D2 receptors in the lateral PFC impairs learning of new stimulus-response associations and cognitive flexibility, but not the memory of highly familiar associations. In addition, D2 receptors may also contribute to motivation. The learning deficits correlated with reductions of neural information about the associations in PFC neurons, alterations in global excitability and spike synchronization, and exaggerated alpha and beta neural oscillations. Our findings provide new insights into how DA transmission modulates associative learning and memory processes in frontostriatal systems. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making

Directory of Open Access Journals (Sweden)

Regina A. Weilbächer

2016-12-01

Full Text Available Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making.

Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.

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Kegeles, Lawrence S; Mao, Xiangling; Stanford, Arielle D; Girgis, Ragy; Ojeil, Najate; Xu, Xiaoyan; Gil, Roberto; Slifstein, Mark; Abi-Dargham, Anissa; Lisanby, Sarah H; Shungu, Dikoma C

2012-05-01

Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. Case-control study. Inpatient psychiatric research unit and associated outpatient clinic. Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with

Converging evidence for the association of functional genetic variation in the serotonin receptor 2a gene with prefrontal function and olanzapine treatment.

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Blasi, Giuseppe; De Virgilio, Caterina; Papazacharias, Apostolos; Taurisano, Paolo; Gelao, Barbara; Fazio, Leonardo; Ursini, Gianluca; Sinibaldi, Lorenzo; Andriola, Ileana; Masellis, Rita; Romano, Raffaella; Rampino, Antonio; Di Giorgio, Annabella; Lo Bianco, Luciana; Caforio, Grazia; Piva, Francesco; Popolizio, Teresa; Bellantuono, Cesario; Todarello, Orlando; Kleinman, Joel E; Gadaleta, Gemma; Weinberger, Daniel R; Bertolino, Alessandro

2013-09-01

Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects. To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine. In silico predictions, in vitro, and case-control investigations. Academic and clinical facilities. The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. EXPOSURES Patients received olanzapine monotherapy for 8 weeks. In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia. Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment. Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and

Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

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Nair, Sunila G; Gudelsky, Gary A

2004-09-15

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

Prefrontal Dopamine D1 Receptors and Working Memory in Schizotypal Personality Disorder: A PET Study with [11C]NNC112

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Thompson, Judy L.; Rosell, Daniel R.; Slifstein, Mark; Girgis, Ragy R.; Xu, Xiaoyan; Ehrlich, Yosefa; Kegeles, Lawrence S.; Hazlett, Erin A.; Abi-Dargham, Anissa; Siever, Larry J.

2014-01-01

Rationale Schizotypal personality disorder (SPD) is associated with working memory (WM) impairments that are similar to those observed in schizophrenia. Imaging studies have suggested that schizophrenia is associated with alterations in dopamine D1-receptor availability in the prefrontal cortex (PFC) that may be related to the WM impairments that characterize this disorder. Objectives To characterize prefrontal D1-receptor availability and its relation to WM performance in SPD. Methods We used positron emission tomography (PET) and the radiotracer [11C]NNC112 with 18 unmedicated SPD and 21 healthy-control participants; as an index of D1-receptor availability, binding-potential (BP) measures (BPF, BPND, and BPP) were calculated for prefrontal and striatal subregions. To assess WM, SPD participants completed the 2-back and Paced Auditory Serial Addition Test (PASAT). Results There were no significant group differences in PFC BP. BPF and BPP in the medial PFC were significantly negatively related to PASAT performance (rs=-0.551, p=.022 and rs=-0.488, p=.047, respectively), but BP was not related to 2-back performance. Conclusions In contrast to what has been found in schizophrenia, SPD was not associated with significant prefrontal D1-receptor alterations. Similar to previous schizophrenia findings, however, higher prefrontal D1-receptor availability was associated with poorer WM performance (as measured by the PASAT) in SPD. These findings suggest that schizophrenia and SPD may share a common pathophysiological feature related to prefrontal dopamine functioning that contributes to WM dysfunction, but that in SPD, alterations in D1 may occur only in a subset of individuals and/or to an extent that is minor relative to what occurs in schizophrenia. PMID:24781514

Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation.

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Alexandra Dumitriu

2012-06-01

Full Text Available Parkinson disease (PD is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9 of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1 transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes, suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs selected from a recent meta-analysis of PD genome-wide association studies (GWAS were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK gene and a probe in the spermine oxidase (SMOX gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.

MPTP-induced executive dysfunction is associated with altered prefrontal serotonergic function.

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Maiti, Panchanan; Gregg, Laura C; McDonald, Michael P

2016-02-01

In Parkinson's disease, cognitive deficits manifest as fronto-striatally-mediated executive dysfunction, with impaired attention, planning, judgment, and impulse control. We examined changes in executive function in mice lesioned with subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a 3-choice serial reaction-time (SRT) task, which included measures of sustained attention and impulse control. Each trial of the baseline SRT task comprised a pseudo-random pre-cue period ranging from 3 to 8 s, followed by a 1-s cue duration. MPTP impaired all measures of impulsive behavior acutely, but with additional training their performance normalized to saline control levels. When challenged with shorter cue durations, MPTP-lesioned mice had significantly slower reaction times than wild-type mice. When challenged with longer pre-cue times, the MPTP-lesioned mice exhibited a loss of impulse control at the longer durations. In lesioned mice, striatal dopamine was depleted by 54% and the number of tyrosine-hydroxylase-positive neurons in the substantia nigra pars compacta was reduced by 75%. Serotonin (5-HT) was unchanged in the striatum and prefrontal cortex (PFC), but the ratio of 5-hydroxyindolacetic acid (5-HIAA) to 5-HT was significantly reduced in the MPTP group in the PFC. In lesioned mice, prefrontal 5-HIAA/5-HT was significantly correlated with the executive impairments and striatal norepinephrine was associated with slower reaction times. None of the neurochemical measures was significantly associated with behavior in saline-treated controls. Taken together, these results show that prefrontal 5-HT turnover may play a pivotal role in MPTP-induced executive dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

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Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

Neural correlates of auditory recognition memory in primate lateral prefrontal cortex.

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Plakke, B; Ng, C-W; Poremba, A

2013-08-06

The neural underpinnings of working and recognition memory have traditionally been studied in the visual domain and these studies pinpoint the lateral prefrontal cortex (lPFC) as a primary region for visual memory processing (Miller et al., 1996; Ranganath et al., 2004; Kennerley and Wallis, 2009). Herein, we utilize single-unit recordings for the same region in monkeys (Macaca mulatta) but investigate a second modality examining auditory working and recognition memory during delayed matching-to-sample (DMS) performance. A large portion of neurons in the dorsal and ventral banks of the principal sulcus (area 46, 46/9) show DMS event-related activity to one or more of the following task events: auditory cues, memory delay, decision wait time, response, and/or reward portions. Approximately 50% of the neurons show evidence of auditory-evoked activity during the task and population activity demonstrated encoding of recognition memory in the form of match enhancement. However, neither robust nor sustained delay activity was observed. The neuronal responses during the auditory DMS task are similar in many respects to those found within the visual working memory domain, which supports the hypothesis that the lPFC, particularly area 46, functionally represents key pieces of information for recognition memory inclusive of decision-making, but regardless of modality. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Single-trial regression elucidates the role of prefrontal theta oscillations in response conflict

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Michael X Cohen

2011-02-01

Full Text Available In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does not in any given trial, whereas some evidence and intuition suggests that conflict may vary in intensity from trial to trial. Here we demonstrate that single-trial multiple regression of time-frequency electrophysiological activity reveals neural mechanisms of cognitive control that are not apparent in cross-trial averages. We also introduce a novel extension to oscillation phase coherence and synchronization analyses, based on weighted phase modulation, that has advantages over standard coherence measures in terms of linking electrophysiological dynamics to trial-varying behavior and experimental variables. After replicating previous response conflict findings using trial-averaged data, we extend these findings using single trial analytic methods to provide novel evidence for the role of medial frontal-lateral prefrontal theta-band synchronization in conflict-induced response time dynamics, including a role for lateral prefrontal theta-band activity in biasing response times according to perceptual conflict. Given that these methods shed new light on the prefrontal mechanisms of response conflict, they are also likely to be useful for investigating other neurocognitive processes.

Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation.

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Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin

2014-04-14

Brain oscillations across all frequency bands play a key role for memory formation. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (∼18 Hz) has been shown to be central for encoding of verbal memories. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dynamic Hippocampal and Prefrontal Contributions to Memory Processes and Representations Blur the Boundaries of Traditional Cognitive Domains

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Rachael D. Rubin; Hillary Schwarb; Heather D. Lucas; Michael R. Dulas; Neal J. Cohen

2017-01-01

The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and tasks that require the flexible use of cognitive and social behavior, including domains traditionally linked to prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal cortex (PFC) has gained traction as a...

Medial prefrontal cortex role in recognition memory in rodents.

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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.

Impaired mixed emotion processing in the right ventrolateral prefrontal cortex in schizophrenia: an fMRI study.

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Szabó, Ádám György; Farkas, Kinga; Marosi, Csilla; Kozák, Lajos R; Rudas, Gábor; Réthelyi, János; Csukly, Gábor

2017-12-08

Schizophrenia has a negative effect on the activity of the temporal and prefrontal cortices in the processing of emotional facial expressions. However no previous research focused on the evaluation of mixed emotions in schizophrenia, albeit they are frequently expressed in everyday situations and negative emotions are frequently expressed by mixed facial expressions. Altogether 37 subjects, 19 patients with schizophrenia and 18 healthy control subjects were enrolled in the study. The two study groups did not differ in age and education. The stimulus set consisted of 10 fearful (100%), 10 happy (100%), 10 mixed fear (70% fear and 30% happy) and 10 mixed happy facial expressions. During the fMRI acquisition pictures were presented in a randomized order and subjects had to categorize expressions by button press. A decreased activation was found in the patient group during fear, mixed fear and mixed happy processing in the right ventrolateral prefrontal cortex (VLPFC) and the right anterior insula (RAI) at voxel and cluster level after familywise error correction. No difference was found between study groups in activations to happy facial condition. Patients with schizophrenia did not show a differential activation between mixed happy and happy facial expression similar to controls in the right dorsolateral prefrontal cortex (DLPFC). Patients with schizophrenia showed decreased functioning in right prefrontal regions responsible for salience signaling and valence evaluation during emotion recognition. Our results indicate that fear and mixed happy/fear processing are impaired in schizophrenia, while happy facial expression processing is relatively intact.

Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

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Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

2015-01-01

Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

The Efficacy of Daily Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for Burning Mouth Syndrome (BMS): A Randomized Controlled Single-blind Study.

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Umezaki, Yojiro; Badran, Bashar W; DeVries, William H; Moss, Jkeonye; Gonzales, Theresa; George, Mark S

2016-01-01

Burning mouth syndrome (BMS) is a burning oral sensation without any corresponding abnormal findings. In some cases, BMS is refractory to pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex induces analgesic effect in both acute and chronic pain. However, its effect for BMS has not been evaluated. The aim of this randomized, controlled, single-blind study was to assess the efficacy of prefrontal rTMS for BMS. Twenty patients with BMS were recruited and randomized to receive 30,000 pulses in total at 10 Hz TMS (n = 12) or sham TMS (n = 8). We assessed the change of BMS pain condition, functional status and mood until 2 months after the beginning of treatment. In the real group, the BMS pain intensity decreased 67%, and 75% of the patients reported >50% pain decrease on final assessment compared to baseline, without heavy side effects. There was significant pain reduction in subjects in the real group immediately after 1 week of treatment, whereas there was none in those in the sham group. Similar tendency was confirmed in change of functional status. Mood and the affective aspect of pain were not changed in this study. BMS pain was significantly improved with 2 weeks of treatment of high frequency rTMS over left DLPFC compared to sham stimulation. Further study is needed to refine and improve TMS as a potential treatment of BMS. Copyright © 2016 Elsevier Inc. All rights reserved.

Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

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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...

Layer-specific modulation of the prefrontal cortex by nicotinic acetylcholine receptors

NARCIS (Netherlands)

Poorthuis, R.B.; Bloem, B.; Schak, B.; Wester, J.; de Kock, C.P.J.; Mansvelder, H.D.

2013-01-01

Acetylcholine signaling through nicotinic receptors (nAChRs) in the prefrontal cortex (PFC) is crucial for attention. Nicotinic AChRs are expressed on glutamatergic inputs to layer V (LV) cells and on LV interneurons and LVI pyramidal neurons. Whether PFC layers are activated by nAChRs to a similar

Orbital and Ventromedial Prefrontal Cortex Functioning in Parkinson's Disease: Neuropsychological Evidence

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Poletti, Michele; Bonuccelli, Ubaldo

2012-01-01

A recent paper (Zald & Andreotti, 2010) reviewed neuropsychological tasks that assess the function of the orbital and ventromedial portions of the prefrontal cortex (OMPFC). Neuropathological studies have shown that the function of the OMPFC should be preserved in the early stages of Parkinson's disease (PD) but becomes affected in the advanced…

A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and extinction in animals

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Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard. J.; Myers, Catherine E.

2012-01-01

Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning. PMID:23164732

Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task

OpenAIRE

Asinof, Samuel K.; Paine, Tracie A.

2012-01-01

Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known. Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of γ-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia. Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parv...

Prefrontal responses to digit span memory phases in patients with post-traumatic stress disorder (PTSD: A functional near infrared spectroscopy study

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Fenghua Tian

2014-01-01

Full Text Available Neuroimaging studies of post-traumatic stress disorder (PTSD-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.

Prefrontal responses to digit span memory phases in patients with post-traumatic stress disorder (PTSD): a functional near infrared spectroscopy study.

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Tian, Fenghua; Yennu, Amarnath; Smith-Osborne, Alexa; Gonzalez-Lima, F; North, Carol S; Liu, Hanli

2014-01-01

Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related) forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.

Lateralized Contribution of Prefrontal Cortex in Controlling Task-Irrelevant Information during Verbal and Spatial Working Memory Tasks: rTMS Evidence

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Sandrini, Marco; Rossini, Paolo Maria; Miniussi, Carlo

2008-01-01

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs.…

Change in emotional self-concept following socio-cognitive training relates to structural plasticity of the prefrontal cortex.

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Lumma, Anna-Lena; Valk, Sofie L; Böckler, Anne; Vrtička, Pascal; Singer, Tania

2018-04-01

Self-referential processing is a key component of the emotional self-concept. Previous studies have shown that emotional self-referential processing is related to structure and function of cortical midline areas such as medial prefrontal cortex (mPFC), and that it can be altered on a behavioral level by specific mental training practices. However, it remains unknown how behavioral training-related change in emotional self-concept content relates to structural plasticity. To address this issue, we examined the relationship between training-induced change in participant's emotional self-concept measured through emotional word use in the Twenty Statement Test and change in cortical thickness in the context of a large-scale longitudinal mental training study called the ReSource Project . Based on prior behavioral findings showing increased emotional word use particularly after socio-cognitive training targeting perspective-taking capacities, this study extended these results by revealing that individual differences in the degree to which participants changed their emotional self-concept after training was positively related to cortical thickness change in right mPFC extending to dorsolateral PFC (dlPFC). Furthermore, increased self-related negative emotional word use after training was positively associated with cortical thickness change in left pars orbitalis and bilateral dlPFC. Our findings reveal training-related structural brain change in regions known to be involved in self-referential processing and cognitive control, and could indicate a relationship between restructuring of the emotional self-concept content as well as reappraisal of negative aspects and cortical thickness change. As such, our findings can guide the development of psychological interventions targeted to alter specific facets of the self-concept.

Context-dependent representation of response-outcome in monkey prefrontal neurons.

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Tsujimoto, Satoshi; Sawaguchi, Toshiyuki

2005-07-01

For behaviour to be purposeful, it is important to monitor the preceding behavioural context, particularly for factors regarding stimulus, response and outcome. The dorsolateral prefrontal cortex (DLPFC) appears to play a major role in such a context-dependent, flexible behavioural control system, and this area is likely to have a neuronal mechanism for such retrospective coding, which associates response-outcome with the information and/or neural systems that guided the response. To address this hypothesis, we recorded neuronal activity from the DLPFC of monkeys performing memory- and sensory-guided saccade tasks, each of which had two conditions with reward contingencies. We found that post-response activity of a subset of DLPFC neurons was modulated by three factors relating to earlier events: the direction of the immediately preceding response, its outcome (reward or non-reward) and the information type (memory or sensory) that guided the response. Such neuronal coding should play a role in associating response-outcome with information and/or neural systems used to guide behaviour - that is, 'retrospective monitoring' of behavioural context and/or neural systems used for guiding behaviour - thereby contributing to context-dependent, flexible control of behaviours.

Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268.

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Kimoto, Sohei; Bazmi, H Holly; Lewis, David A

2014-09-01

Cognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia. The authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes. GAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes. Deficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia.

Prefrontal cortical GABA transmission modulates discrimination and latent inhibition of conditioned fear: relevance for schizophrenia.

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Piantadosi, Patrick T; Floresco, Stan B

2014-09-01

Inhibitory gamma-aminobutyric acid (GABA) transmission within the prefrontal cortex (PFC) regulates numerous functions, and perturbations in GABAergic transmission within this region have been proposed to contribute to some of the cognitive and behavioral abnormalities associated with disorders such as schizophrenia. These abnormalities include deficits in emotional regulation and aberrant attributions of affective salience. Yet, how PFC GABA regulates these types of emotional processes are unclear. To address this issue, we investigated the contribution of PFC GABA transmission to different aspects of Pavlovian emotional learning in rats using translational discriminative fear conditioning and latent inhibition (LI) assays. Reducing prelimbic PFC GABAA transmission via infusions of the antagonist bicuculline before the acquisition or expression of fear conditioning eliminated the ability to discriminate between an aversive conditioned stimulus (CS+) paired with footshock vs a neutral CS-, resembling similar deficits observed in schizophrenic patients. In a separate experiment, blockade of PFC GABAA receptors before CS preexposure (PE) and conditioning did not affect subsequent expression of LI, but did enhance fear in rats that were not preexposed to the CS. In contrast, PFC GABA-blockade before a fear expression test disrupted the recall of learned irrelevance and abolished LI. These data suggest that normal PFC GABA transmission is critical for regulating and mitigating multiple aspects of aversive learning, including discrimination between fear vs safety signals and recall of information about the irrelevance of stimuli. Furthermore, they suggest that similar deficits in emotional regulation observed in schizophrenia may be driven in part by deficient PFC GABA activity.

Autobiographical memory loss following a right prefrontal lobe tumour resection: a case report and review of the literature.

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Jamjoom, A A B; Gallo, P; Kandasamy, J; Phillips, J; Sokol, D

2017-07-01

The right prefrontal lobe has not traditionally been considered eloquent brain. Resection of tumours within this region does not typically lead to permanent functional impairment. In this report, we highlight the case of a patient who developed autobiographical memory loss following an uncomplicated resection of a right prefrontal tumour. A previously fit and well 15-year old presented with a persistent right-sided headache. An MRI demonstrated an expanded right mid-frontal gyrus with changes consistent with a low-grade tumour. The patient underwent a right-sided craniotomy and resection of the lesion which was confirmed as a WHO grade II diffuse astrocytoma. Postoperatively, the patient reported profound retrograde amnesia for a range of memory components, in particular autobiographical memory and semantic memory. Postoperative imaging showed a good resection margin with no evidence of underlying brain injury. Over an 18-month period, the patient showed no improvement in autobiographical memory; however, significant relearning of semantic knowledge took place and her academic performance was found to be in line with expectations for her age. In this report, we discuss a case and review the literature on the role of the right prefrontal cortex in memory and caution on the perception of right prefrontal non-eloquence.

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

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Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions.

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Perry, Jennifer L; Joseph, Jane E; Jiang, Yang; Zimmerman, Rick S; Kelly, Thomas H; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P; Bardo, Michael T

2011-01-01

Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. Copyright © 2010 Elsevier B.V. All rights reserved.

Bupropion Administration Increases Resting-State Functional Connectivity in Dorso-Medial Prefrontal Cortex.

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Rzepa, Ewelina; Dean, Zola; McCabe, Ciara

2017-06-01

Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown. Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity. Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Tangram solved? Prefrontal cortex activation analysis during geometric problem solving.

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Ayaz, Hasan; Shewokis, Patricia A; Izzetoğlu, Meltem; Çakır, Murat P; Onaral, Banu

2012-01-01

Recent neuroimaging studies have implicated prefrontal and parietal cortices for mathematical problem solving. Mental arithmetic tasks have been used extensively to study neural correlates of mathematical reasoning. In the present study we used geometric problem sets (tangram tasks) that require executive planning and visuospatial reasoning without any linguistic representation interference. We used portable optical brain imaging (functional near infrared spectroscopy--fNIR) to monitor hemodynamic changes within anterior prefrontal cortex during tangram tasks. Twelve healthy subjects were asked to solve a series of computerized tangram puzzles and control tasks that required same geometric shape manipulation without problem solving. Total hemoglobin (HbT) concentration changes indicated a significant increase during tangram problem solving in the right hemisphere. Moreover, HbT changes during failed trials (when no solution found) were significantly higher compared to successful trials. These preliminary results suggest that fNIR can be used to assess cortical activation changes induced by geometric problem solving. Since fNIR is safe, wearable and can be used in ecologically valid environments such as classrooms, this neuroimaging tool may help to improve and optimize learning in educational settings.

Inequality signals in dorsolateral prefrontal cortex inform social preference models.

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Holper, Lisa; Burke, Christopher J; Fausch, Christoph; Seifritz, Erich; Tobler, Philippe N

2018-05-01

Humans typically display inequality aversion in social situations, which manifests itself as a preference for fairer distributions of resources. However, people differ in the degree to which they dislike being worse off [disadvantageous inequality (DI) aversion] or better off [advantageous inequality (AI) aversion] than others. Competing models explain such behavior by focusing on aversion to payoff differences, maximization of total payoff or reciprocity. Using functional near-infrared spectroscopy, we asked which of these theories could better explain dorsolateral prefrontal cortex (dlPFC) activity while participants accepted or punished fair vs unfair monetary transfers in an anonymous norm compliance task. We found that while all participants exhibited DI aversion, there were substantial differences in preferences for AI, which were strongly predicted by dlPFC activation. Model comparisons revealed that both punishment behavior and prefrontal activity were best explained by a model that allowed for AI seeking rather than imposing aversion. Moreover, enhancing this model by taking into account behavioral response times, as a proxy for choice difficulty, further improved model fits. Our data provide evidence that the dlPFC encodes subjective values of payoff inequality and that this representation is richer than envisaged by standard models of social preferences.

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.

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Clarke, Hannah F; Horst, Nicole K; Roberts, Angela C

2015-03-31

Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach-avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala-anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

Hyper-Connectivity and Hyper-Plasticity in the Medial Prefrontal Cortex in the Valproic Acid Animal Model of Autism

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Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

2008-01-01

The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. Th...

Process-specific analysis in episodic memory retrieval using fast optical signals and hemodynamic signals in the right prefrontal cortex

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Dong, Sunghee; Jeong, Jichai

2018-02-01

Objective. Memory is formed by the interaction of various brain functions at the item and task level. Revealing individual and combined effects of item- and task-related processes on retrieving episodic memory is an unsolved problem because of limitations in existing neuroimaging techniques. To investigate these issues, we analyze fast and slow optical signals measured from a custom-built continuous wave functional near-infrared spectroscopy (CW-fNIRS) system. Approach. In our work, we visually encode the words to the subjects and let them recall the words after a short rest. The hemodynamic responses evoked by the episodic memory are compared with those evoked by the semantic memory in retrieval blocks. In the fast optical signal, we compare the effects of old and new items (previously seen and not seen) to investigate the item-related process in episodic memory. The Kalman filter is simultaneously applied to slow and fast optical signals in different time windows. Main results. A significant task-related HbR decrease was observed in the episodic memory retrieval blocks. Mean amplitude and peak latency of a fast optical signal are dependent upon item types and reaction time, respectively. Moreover, task-related hemodynamic and item-related fast optical responses are correlated in the right prefrontal cortex. Significance. We demonstrate that episodic memory is retrieved from the right frontal area by a functional connectivity between the maintained mental state through retrieval and item-related transient activity. To the best of our knowledge, this demonstration of functional NIRS research is the first to examine the relationship between item- and task-related memory processes in the prefrontal area using single modality.

Process-specific analysis in episodic memory retrieval using fast optical signals and hemodynamic signals in the right prefrontal cortex.

Science.gov (United States)

Dong, Sunghee; Jeong, Jichai

2018-02-01

Memory is formed by the interaction of various brain functions at the item and task level. Revealing individual and combined effects of item- and task-related processes on retrieving episodic memory is an unsolved problem because of limitations in existing neuroimaging techniques. To investigate these issues, we analyze fast and slow optical signals measured from a custom-built continuous wave functional near-infrared spectroscopy (CW-fNIRS) system. In our work, we visually encode the words to the subjects and let them recall the words after a short rest. The hemodynamic responses evoked by the episodic memory are compared with those evoked by the semantic memory in retrieval blocks. In the fast optical signal, we compare the effects of old and new items (previously seen and not seen) to investigate the item-related process in episodic memory. The Kalman filter is simultaneously applied to slow and fast optical signals in different time windows. A significant task-related HbR decrease was observed in the episodic memory retrieval blocks. Mean amplitude and peak latency of a fast optical signal are dependent upon item types and reaction time, respectively. Moreover, task-related hemodynamic and item-related fast optical responses are correlated in the right prefrontal cortex. We demonstrate that episodic memory is retrieved from the right frontal area by a functional connectivity between the maintained mental state through retrieval and item-related transient activity. To the best of our knowledge, this demonstration of functional NIRS research is the first to examine the relationship between item- and task-related memory processes in the prefrontal area using single modality.

Left Prefrontal Activity Reflects the Ability of Vicarious Fear Learning: A Functional Near-Infrared Spectroscopy Study

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Qingguo Ma

2013-01-01

Full Text Available Fear could be acquired indirectly via social observation. However, it remains unclear which cortical substrate activities are involved in vicarious fear transmission. The present study was to examine empathy-related processes during fear learning by-proxy and to examine the activation of prefrontal cortex by using functional near-infrared spectroscopy. We simultaneously measured participants’ hemodynamic responses and skin conductance responses when they were exposed to a movie. In this movie, a demonstrator (i.e., another human being was receiving a classical fear conditioning. A neutral colored square paired with shocks (CSshock and another colored square paired with no shocks (CSno-shock were randomly presented in front of the demonstrator. Results showed that increased concentration of oxygenated hemoglobin in left prefrontal cortex was observed when participants watched a demonstrator seeing CSshock compared with that exposed to CSno-shock. In addition, enhanced skin conductance responses showing a demonstrator's aversive experience during learning object-fear association were observed. The present study suggests that left prefrontal cortex, which may reflect speculation of others’ mental state, is associated with social fear transmission.

Left prefrontal activity reflects the ability of vicarious fear learning: a functional near-infrared spectroscopy study.

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Ma, Qingguo; Huang, Yujing; Wang, Lei

2013-01-01

Fear could be acquired indirectly via social observation. However, it remains unclear which cortical substrate activities are involved in vicarious fear transmission. The present study was to examine empathy-related processes during fear learning by-proxy and to examine the activation of prefrontal cortex by using functional near-infrared spectroscopy. We simultaneously measured participants' hemodynamic responses and skin conductance responses when they were exposed to a movie. In this movie, a demonstrator (i.e., another human being) was receiving a classical fear conditioning. A neutral colored square paired with shocks (CS(shock)) and another colored square paired with no shocks (CS(no-shock)) were randomly presented in front of the demonstrator. Results showed that increased concentration of oxygenated hemoglobin in left prefrontal cortex was observed when participants watched a demonstrator seeing CS(shock) compared with that exposed to CS(no-shock). In addition, enhanced skin conductance responses showing a demonstrator's aversive experience during learning object-fear association were observed. The present study suggests that left prefrontal cortex, which may reflect speculation of others' mental state, is associated with social fear transmission.

The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

Directory of Open Access Journals (Sweden)

Pedro F. M. Ribeiro

2013-09-01

Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

Prefrontal Cortex Lesions and Sex Differences in Fear Extinction and Perseveration

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Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

2010-01-01

Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

Preliminary appraisal of the geohydrologic aspects of drainage wells, Orlando area, central Florida

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Kimrey, Joel O.

1978-01-01

The Floridan aquifer contains two highly transmissive cavernous zones in the Orlando area: an upper producing zone about 150-600 feet below land surface; and a lower producing zone about 1,100-1,500 feet below land surface. Natural head differences are downward and there is hydraulic connection between the two producing zones. Drainage wells are finished open-end into the upper producing zone and emplace surface waters directly into that zone by gravity. Quantitatively, their use constitutes an effective method of artificial recharge. Their negative aspects relate to the probably poor, but unknown, quality of the recharge water. Caution is suggested in drawing definite and final conclusions on the overall geohydrologic and environmental effects of drainage wells prior to the collection and interpretation of a considerable quantity of new data. Though few ground-water pollution problems have been documented to date, the potential for such pollution should be seriously considered in light of the prob-able continuing need to use drainage wells; the probable volumes and quality of water involved; and the hydraulic relations between the two producing zones.

Coding of vocalizations by single neurons in ventrolateral prefrontal cortex.

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Plakke, Bethany; Diltz, Mark D; Romanski, Lizabeth M

2013-11-01

Neuronal activity in single prefrontal neurons has been correlated with behavioral responses, rules, task variables and stimulus features. In the non-human primate, neurons recorded in ventrolateral prefrontal cortex (VLPFC) have been found to respond to species-specific vocalizations. Previous studies have found multisensory neurons which respond to simultaneously presented faces and vocalizations in this region. Behavioral data suggests that face and vocal information are inextricably linked in animals and humans and therefore may also be tightly linked in the coding of communication calls in prefrontal neurons. In this study we therefore examined the role of VLPFC in encoding vocalization call type information. Specifically, we examined previously recorded single unit responses from the VLPFC in awake, behaving rhesus macaques in response to 3 types of species-specific vocalizations made by 3 individual callers. Analysis of responses by vocalization call type and caller identity showed that ∼19% of cells had a main effect of call type with fewer cells encoding caller. Classification performance of VLPFC neurons was ∼42% averaged across the population. When assessed at discrete time bins, classification performance reached 70 percent for coos in the first 300 ms and remained above chance for the duration of the response period, though performance was lower for other call types. In light of the sub-optimal classification performance of the majority of VLPFC neurons when only vocal information is present, and the recent evidence that most VLPFC neurons are multisensory, the potential enhancement of classification with the addition of accompanying face information is discussed and additional studies recommended. Behavioral and neuronal evidence has shown a considerable benefit in recognition and memory performance when faces and voices are presented simultaneously. In the natural environment both facial and vocalization information is present simultaneously and

Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

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Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

2017-05-23

Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.

The effects of vision-related aspects on noise perception of wind turbines in quiet areas.

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Maffei, Luigi; Iachini, Tina; Masullo, Massimiliano; Aletta, Francesco; Sorrentino, Francesco; Senese, Vincenzo Paolo; Ruotolo, Francesco

2013-04-26

Preserving the soundscape and geographic extension of quiet areas is a great challenge against the wide-spreading of environmental noise. The E.U. Environmental Noise Directive underlines the need to preserve quiet areas as a new aim for the management of noise in European countries. At the same time, due to their low population density, rural areas characterized by suitable wind are considered appropriate locations for installing wind farms. However, despite the fact that wind farms are represented as environmentally friendly projects, these plants are often viewed as visual and audible intruders, that spoil the landscape and generate noise. Even though the correlations are still unclear, it is obvious that visual impacts of wind farms could increase due to their size and coherence with respect to the rural/quiet environment. In this paper, by using the Immersive Virtual Reality technique, some visual and acoustical aspects of the impact of a wind farm on a sample of subjects were assessed and analyzed. The subjects were immersed in a virtual scenario that represented a situation of a typical rural outdoor scenario that they experienced at different distances from the wind turbines. The influence of the number and the colour of wind turbines on global, visual and auditory judgment were investigated. The main results showed that, regarding the number of wind turbines, the visual component has a weak effect on individual reactions, while the colour influences both visual and auditory individual reactions, although in a different way.

Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

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Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

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Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

2017-10-01

Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.

Theta–gamma coordination between anterior cingulate and prefrontal cortex indexes correct attention shifts

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Voloh, Benjamin; Valiante, Taufik A.; Everling, Stefan; Womelsdorf, Thilo

2015-01-01

Anterior cingulate and lateral prefrontal cortex (ACC/PFC) are believed to coordinate activity to flexibly prioritize the processing of goal-relevant over irrelevant information. This between-area coordination may be realized by common low-frequency excitability changes synchronizing segregated high-frequency activations. We tested this coordination hypothesis by recording in macaque ACC/PFC during the covert utilization of attention cues. We found robust increases of 5–10 Hz (theta) to 35–55 Hz (gamma) phase–amplitude correlation between ACC and PFC during successful attention shifts but not before errors. Cortical sites providing theta phases (i) showed a prominent cue-induced phase reset, (ii) were more likely in ACC than PFC, and (iii) hosted neurons with burst firing events that synchronized to distant gamma activity. These findings suggest that interareal theta–gamma correlations could follow mechanistically from a cue-triggered reactivation of rule memory that synchronizes theta across ACC/PFC. PMID:26100868

Aspects regarding environmental impact of oil marine platforms from Black sea coast - Romanian area

International Nuclear Information System (INIS)

Szabo, N.

2005-01-01

Full text : As a result of investigations conducted by R.A.PETROM - PETROMAR Constanta subsidiary, reserves of oil and gas in geological structures LEBADA, EOCEN - LEBADA and SINOE from romanian sector of Black Sea Continental Platform, have been discovered. These reserves are exploited by marine platforms and ways of oil transportation to the shore are submarine pipe-lines and ships. To assess environmental impact of oil transportation, studies covered following steps; Characterization of the present status of environmental factors, in the range of pipe-lines and ships; Marine water characterization: salinity, ionic composition, dissolved gases, organic depositions on metallic bodies; Marine bicenosys: phytoplankton and zooplankton characteristics, phytobenthos and zoobenthos communities, marine ichtyofauna, marine mammals. Marine resources available for exploitation; Total radioactivity analysis results; Marine water hydrocarbons analysis results; Present pollution sources in the area; Air quality in oil marine platforms area and shore area; Potential pollution sources and pollutants resulted from oil products transport between marine platforms and shore; Sources and emissions in air; Sources and emissions in marine environment; Aspects regarding waste management; Environmental impact of oil products transport between marine platforms and shore; Impact on the air quality and marine environment of oil marine platforms activities; Assessment of environmental impact on atmosphere generated by the oil products transport between marine platforms and shore; Impact on the marine environment of oil transport ships; Effects of oil fractions on marine organisms; Acute effects of oil pollution on marine communities; Risks of causing major environmental impact accidents/failures on marine platforms PETROMAR; Chronic effects of low oil concentrations;Marine environment recovery potential after discharges accidents

Behavioral aspects of Lutzomyia longipalpis (Diptera: Psychodidae) in urban area endemic for visceral leishmaniasis.

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De Oliveira, E F; Silva, E A; Casaril, A E; Fernandes, C E S; Paranhos Filho, A C; Gamarra, R M; Ribeiro, A A; Brazil, R P; Oliveira, A G

2013-03-01

The study of some of the behavioral aspects of the main vector of Leishmania infantum chagasi Cunha & Chagas in the Americas, Lutzomyia longipalpis (Lutz & Neiva), such as dispersion, population size, and vector survival rates, is important for the elucidation of the mechanisms of visceral leishmaniasis transmission. These parameters were studied by means of capture-mark-release-recapture experiments in an urban area of Campo Grande municipality, an endemic area of visceral leishmaniasis, situated in Mato Grosso do Sul state, Brazil. Six capture-mark-release-recapture experiments were undertaken between November 2009 and November 2010 and once in January 2012 with a view to assessing the population size and survival rate of Lu. longipalpis. The insects were released in a peridomicile surrounded by 13 residences. The recaptures were undertaken with automatic light traps for four consecutive weeks after release in the surrounding area. In total, 3,354 sand flies were captured, marked, and released. The overall recapture rate during the capture-mark-release-recapture experiments was 4.23%, of which 92.45% were recaptured at the release site, indicating limited dispersal. The greatest distance recorded from the release site was 165 m for males and 241 m for females. The male daily survival rate, calculated on the basis of regressions from the numbers of marked recaptured insects during the 15 successive days after release was 0.897. The estimated male population size measured by the Lincoln Index was 10,947.127. Though Lu. longipalpis presented a limited dispersion the physical barriers typical of urban environments did not prevent the sand flies from flying long distances.

Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

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Bunce, Jamie G; Zikopoulos, Basilis; Feinberg, Marcia; Barbas, Helen

2013-12-15

To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. Copyright © 2013 Wiley Periodicals, Inc.

Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

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Cui Guang-bin

2012-02-01

Full Text Available Abstract Background Interleukin-8 (IL-8 is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC, is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. Findings In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC, and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. Conclusions Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

Noradrenergic action in prefrontal cortex in the late stage of memory consolidation

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Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

2004-01-01

These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively

Decoding the dopamine signal in macaque prefrontal cortex: a simulation study using the Cx3Dp simulator.

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Isabelle Ayumi Spühler

Full Text Available Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated 'teaching' signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson's disease, or induced through drugs blocking dopamine reuptake.

[Effect of Reading a Book on a Tablet Computer on Cerebral Blood Flow in the Prefrontal Cortex].

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Sugiura, Akihiro; Eto, Takuya; Kinoshita, Fumiya; Takada, Hiroki

2018-01-01

By measuring cerebral blood flow in the prefrontal cortex, we aimed to determine how reading a book on a tablet computer affects sleep. Seven students (7 men age range, 21-32 years) participated in this study. In a controlled illuminance environment, the subjects read a novel in printed form or on a tablet computer from any distance. As the subjects were reading, the cerebral blood flow in their prefrontal cortex was measured by near-infrared spectroscopy. The study protocol was as follows. 1) Subjects mentally counted a sequence of numbers for 30 s as a pretest to standardized thinking and then 2) read the novel for 10 min, using the printed book or tablet computer. In step 2), the use of the book or tablet computer was in a random sequence. Subjects rested between the two tasks. Significantly increased brain activity (increase in regional cerebral blood flow) was observed following reading a novel on a tablet computer compared with that after reading a printed book. Furthermore, the region around Broca's area was more active when reading on a tablet computer than when reading a printed book. Considering the results of this study and previous studies on physiological characteristics during nonrapid eye movement sleep, we concluded that reading a book on a tablet computer before the onset of sleep leads to the potential inhibition of sound sleep through mechanisms other than the suppression of melatonin secretion.

Decoding the Dopamine Signal in Macaque Prefrontal Cortex: A Simulation Study Using the Cx3Dp Simulator

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Spühler, Isabelle Ayumi; Hauri, Andreas

2013-01-01

Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake. PMID:23951205

Brain cells in the avian 'prefrontal cortex' code for features of slot-machine-like gambling.

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Damian Scarf

2011-01-01

Full Text Available Slot machines are the most common and addictive form of gambling. In the current study, we recorded from single neurons in the 'prefrontal cortex' of pigeons while they played a slot-machine-like task. We identified four categories of neurons that coded for different aspects of our slot-machine-like task. Reward-Proximity neurons showed a linear increase in activity as the opportunity for a reward drew near. I-Won neurons fired only when the fourth stimulus of a winning (four-of-a-kind combination was displayed. I-Lost neurons changed their firing rate at the presentation of the first nonidentical stimulus, that is, when it was apparent that no reward was forthcoming. Finally, Near-Miss neurons also changed their activity the moment it was recognized that a reward was no longer available, but more importantly, the activity level was related to whether the trial contained one, two, or three identical stimuli prior to the display of the nonidentical stimulus. These findings not only add to recent neurophysiological research employing simulated gambling paradigms, but also add to research addressing the functional correspondence between the avian NCL and primate PFC.

Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation.

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Armita Golkar

Full Text Available The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC and the lateral orbitofrontal cortex (OFC contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

Impaired Prefrontal-Amygdala Pathway, Self-Reported Emotion, and Erection in Psychogenic Erectile Dysfunction Patients With Normal Nocturnal Erection

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Jianhuai Chen

2018-04-01

Full Text Available Background: Neuroimaging studies have demonstrated that the prefrontal cortex and amygdala play an important role in sexual arousal (SA. However, little is known about the interactions between the prefrontal and cortex amygdala, which mediate the cognitive regulation of emotion and SA.Objective: We seek to determine whether nocturnal erection of psychogenic erectile dysfunction (pED patients are normal and whether there are changes of topological organization in the prefrontal-amygdala pathway of brain network in pED. In addition, whether there are correlations between network property changes and self-reported emotion and erection.Design, setting, and participants: We used the RigiScan device to evaluate erectile function of patients and employed diffusion MRI and graph theory to construct brain networks of 21 pED patients and 24 healthy controls.Outcome measurements and statistical analysis: We considered four nodal metrics and their asymmetry scores, and nocturnal penile tumescence (NPT parameters, to evaluate the topological properties of brain networks of pED and their relationships with the impaired self-reported emotion and erection.Results and limitations: All the pED patients showed normal nocturnal penile erection, however impaired self-reported erection and negative emotion. In addition, patients showed lower connectivity degree and strength in the left prefrontal-amygdala pathway. We also found that pED exhibited lower leftward asymmetry in the inferior frontal gyrus. Furthermore, patients showed more hub regions and fewer pivotal connections. Moreover, the degree of the left amygdala of pED showed significantly negative correlation with the self-reported erection and positive correlation with the self-reported negative emotion.Conclusions: Together, these results suggest normal nocturnal erection in pED. However, abnormalities of brain network organization in pED, particularly in the left prefrontal-amygdala pathway, are associated

Impaired Prefrontal-Amygdala Pathway, Self-Reported Emotion, and Erection in Psychogenic Erectile Dysfunction Patients With Normal Nocturnal Erection

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Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-01-01

Background: Neuroimaging studies have demonstrated that the prefrontal cortex and amygdala play an important role in sexual arousal (SA). However, little is known about the interactions between the prefrontal and cortex amygdala, which mediate the cognitive regulation of emotion and SA. Objective: We seek to determine whether nocturnal erection of psychogenic erectile dysfunction (pED) patients are normal and whether there are changes of topological organization in the prefrontal-amygdala pathway of brain network in pED. In addition, whether there are correlations between network property changes and self-reported emotion and erection. Design, setting, and participants: We used the RigiScan device to evaluate erectile function of patients and employed diffusion MRI and graph theory to construct brain networks of 21 pED patients and 24 healthy controls. Outcome measurements and statistical analysis: We considered four nodal metrics and their asymmetry scores, and nocturnal penile tumescence (NPT) parameters, to evaluate the topological properties of brain networks of pED and their relationships with the impaired self-reported emotion and erection. Results and limitations: All the pED patients showed normal nocturnal penile erection, however impaired self-reported erection and negative emotion. In addition, patients showed lower connectivity degree and strength in the left prefrontal-amygdala pathway. We also found that pED exhibited lower leftward asymmetry in the inferior frontal gyrus. Furthermore, patients showed more hub regions and fewer pivotal connections. Moreover, the degree of the left amygdala of pED showed significantly negative correlation with the self-reported erection and positive correlation with the self-reported negative emotion. Conclusions: Together, these results suggest normal nocturnal erection in pED. However, abnormalities of brain network organization in pED, particularly in the left prefrontal-amygdala pathway, are associated with the

DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine.

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Gelao, Barbara; Fazio, Leonardo; Selvaggi, Pierluigi; Di Giorgio, Annabella; Taurisano, Paolo; Quarto, Tiziana; Romano, Raffaella; Porcelli, Annamaria; Mancini, Marina; Masellis, Rita; Ursini, Gianluca; De Simeis, Giuseppe; Caforio, Grazia; Ferranti, Laura; Lo Bianco, Luciana; Rampino, Antonio; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2014-06-01

Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p < 0.05, family-wise error corrected) was used. On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.

Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

NARCIS (Netherlands)

Crunelle, Cleo L.; Kaag, Anne Marije; van den Munkhof, Hanna E.; Reneman, Liesbeth; Homberg, Judith R.; Sabbe, Bernard; van den Brink, Wim; van Wingen, Guido

2015-01-01

Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal

Reward-dependent modulation of working memory in lateral prefrontal cortex.

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Kennerley, Steven W; Wallis, Jonathan D

2009-03-11

Although research implicates lateral prefrontal cortex (PFC) in executive control and goal-directed behavior, it remains unclear how goals influence executive processes. One possibility is that goal-relevant information, such as expected rewards, could modulate the representation of information relating to executive control, thereby ensuring the efficient allocation of cognitive resources. To investigate this, we examined how reward modulated spatial working memory. Past studies investigating spatial working memory have focused on dorsolateral PFC, but this area only weakly connects with areas processing reward. Ventrolateral PFC has better connections in this regard. Thus, we contrasted the functional properties of single neurons in ventrolateral and dorsolateral PFC as two subjects performed a task that required them to hold spatial information in working memory under different expectancies of reward for correct performance. We balanced the order of presentation of spatial and reward information so we could assess the neuronal encoding of the two pieces of information independently and conjointly. Neurons in ventrolateral PFC encoded both spatial and reward information earlier, stronger and in a more sustained manner than neurons in dorsolateral PFC. Within ventrolateral PFC, spatial selectivity was more prevalent on the inferior convexity than within the principal sulcus. Finally, when reward increased spatial selectivity, behavioral performance improved, whereas when reward decreased spatial selectivity, behavioral performance deteriorated. These results suggest that ventrolateral PFC may be a locus whereby information about expected rewards can modulate information in working memory. The pattern of results is consistent with a role for ventrolateral PFC in attentional control.

Perceptual decision-making difficulty modulates feedforward effective connectivity to the dorsolateral prefrontal cortex

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Bidhan eLamichhane

2015-09-01

Full Text Available Diverse cortical structures are known to coordinate activity as a network in relaying and processing of visual information to discriminate visual objects. However, how this discrimination is achieved is still largely unknown. To contribute to answering this question, we used face-house categorization tasks with three levels of noise in face and house images in functional magnetic resonance imaging (fMRI experiments involving thirty-three participants. The behavioral performance error and response time (RT were correlated with noise in face-house images. We then built dynamical causal models (DCM of fMRI blood-oxygenation level dependent (BOLD signals from the face and house category-specific regions in ventral temporal cortex, the fusiform face area (FFA and parahippocampal place area (PPA, and the dorsolateral prefrontal cortex (dlPFC. We found a strong feed-forward intrinsic connectivity pattern from FFA and PPA to dlPFC. Importantly, the feed-forward connectivity to dlPFC was significantly modulated by the perception of both faces and houses. The dlPFC-BOLD activity, the connectivity from FFA and PPA to the dlPFC all increased with noise level. These results suggest that the FFA-PPA-dlPFC network plays an important role for relaying and integrating competing sensory information to arrive at perceptual decisions.

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

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Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

2010-02-22

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

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Alessandro Bertolino

2010-02-01

Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Lateral, Not Medial, Prefrontal Cortex Contributes to Punishment and Aversive Instrumental Learning

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Jean-Richard-dit-Bressel , Philip; McNally, Gavan P.

2016-01-01

Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral…

Modulation of the Left Prefrontal Cortex with High Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis

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Amer M. Burhan

2015-01-01

Full Text Available Multiple Sclerosis (MS is a chronic central nervous system (CNS demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F3 location (using 10-20 electroencephalography (EEG lead localization system. GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t-test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.

Reduced prefrontal cortical gray matter volume in young adults exposed to harsh corporal punishment.

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Tomoda, Akemi; Suzuki, Hanako; Rabi, Keren; Sheu, Yi-Shin; Polcari, Ann; Teicher, Martin H

2009-08-01

Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). 1455 young adults (18-25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3 T trio scanner. GMV was reduced by 19.1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P=0.037, corrected cluster level), by 14.5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA9) (P=0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA24) (P<0.001, uncorrected cluster level) of HCP subjects. There were significant correlations between GMV in these identified regions and performance IQ on the WAIS-III. Exposing children to harsh HCP may have detrimental effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP.

Localization of cortical areas activated by thinking.

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Roland, P E; Friberg, L

1985-05-01

These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work in the form of operations on internal information, done by an awake subject. The rCBF was measured in 254 cortical regions in 11 subjects with the intracarotid 133Xe injection technique. In normal man, changes in the regional cortical metabolic rate of O2 leads to proportional changes in rCBF. One control study was taken with the subjects at rest. Then the rCBF was measured during three different simple algorithm tasks, each consisting of retrieval of a specific memory followed by a simple operation on the retrieved information. Once started, the information processing went on in the brain without any communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined that they started at their front door and then walked alternatively to the left or the right each time they reached a corner. The rCBF increased only in homotypical cortical areas during thinking. The areas in the superior prefrontal cortex increased their rCBF equivalently during the three types of thinking. In the remaining parts of the prefrontal cortex there were multifocal increases of rCBF. The localizations and intensities of these rCBF increases depended on the type of internal operation occurring. The rCBF increased bilaterally in the angular cortex during 50-3 thinking. The rCBF increased in the right midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and

Personality disorder symptomatology is associated with anomalies in striatal and prefrontal morphology.

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Payer, Doris E; Park, Min Tae M; Kish, Stephen J; Kolla, Nathan J; Lerch, Jason P; Boileau, Isabelle; Chakravarty, M M

2015-01-01

Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness/surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects. Subjects reporting PD-Sx were then grouped into symptom-based clusters: N = 20 into Cluster B (reporting Antisocial, Borderline, Histrionic, or Narcissistic PD-Sx) and N = 28 into Cluster C (reporting Obsessive-Compulsive, Avoidant, or Dependent PD-Sx); N = 11 subjects reported PD-Sx from both clusters, and none reported Cluster A (Paranoid, Schizoid, or Schizotypal) PD-Sx. Compared to control, Cluster C PD-Sx was associated with greater striatal surface area localized to the caudate tail, smaller ventral striatum volumes, and greater cortical thickness in right prefrontal cortex. Both Cluster B and C PD-Sx groups also showed trends toward greater posterior caudate volumes and orbitofrontal surface area anomalies, but these findings did not survive correction for multiple comparisons. The results point to morphological abnormalities that could contribute to Cluster C PD-Sx. In addition, the observations parallel those in substance use disorders, pointing to the importance of considering PD-Sx when interpreting findings in often-comorbid psychiatric disorders.

Coordinated cell type-specific epigenetic remodeling in prefrontal cortex begins before birth and continues into early adulthood.

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Hennady P Shulha

2013-04-01

Full Text Available Development of prefrontal and other higher-order association cortices is associated with widespread changes in the cortical transcriptome, particularly during the transitions from prenatal to postnatal development, and from early infancy to later stages of childhood and early adulthood. However, the timing and longitudinal trajectories of neuronal gene expression programs during these periods remain unclear in part because of confounding effects of concomitantly occurring shifts in neuron-to-glia ratios. Here, we used cell type-specific chromatin sorting techniques for genome-wide profiling of a histone mark associated with transcriptional regulation--H3 with trimethylated lysine 4 (H3K4me3--in neuronal chromatin from 31 subjects from the late gestational period to 80 years of age. H3K4me3 landscapes of prefrontal neurons were developmentally regulated at 1,157 loci, including 768 loci that were proximal to transcription start sites. Multiple algorithms consistently revealed that the overwhelming majority and perhaps all of developmentally regulated H3K4me3 peaks were on a unidirectional trajectory defined by either rapid gain or loss of histone methylation during the late prenatal period and the first year after birth, followed by similar changes but with progressively slower kinetics during early and later childhood and only minimal changes later in life. Developmentally downregulated H3K4me3 peaks in prefrontal neurons were enriched for Paired box (Pax and multiple Signal Transducer and Activator of Transcription (STAT motifs, which are known to promote glial differentiation. In contrast, H3K4me3 peaks subject to a progressive increase in maturing prefrontal neurons were enriched for activating protein-1 (AP-1 recognition elements that are commonly associated with activity-dependent regulation of neuronal gene expression. We uncovered a developmental program governing the remodeling of neuronal histone methylation landscapes in the prefrontal

Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

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Chun Yang

2012-01-01

Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

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Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun

2007-01-01

Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8±0.75 y, 5 IGAs: male, 22.6±2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA

Mathematical aspects that extend the notion of scientific notation in the area of Physics of General Middle Education

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Yohan Godoy

2018-01-01

Full Text Available For this work, a constructivist didactic proposal was designed in which the students of the third year of General Media Education can acquire a significant learning in the use of Scientific Notation. The type of research used is among feasible projects with a non-experimental field design. For data collection, the survey technique was used, which was applied to 43 students of the Physics subject of the third year of the Liceo Rosario Almarza Trujillo-Venezuela. The analysis of the results indicated that they present deficiencies in terms of significant numbers and order magnitude, which are essential mathematical aspects for the understanding and use of Scientific Notation in the area of Physics, as well as highlighting the need for Implement other teaching and learning strategies, such as a series of complementary activities for the teacher in the classroom or the student. In view of these results, a didactic guide was carried out using the known mathematical aspects and various ludic activities to extend the notion and use of scientific notation.

The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen

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Chen, Xingui; Tao, Longxiang; Li, Jingjing; Wu, Jiaonan; Zhu, Chunyan; Yu, Fengqiong; Zhang, Lei; Zhang, Jingjie; Qiu, Bensheng; Yu, Yongqiang; He, Xiaoxuan

2017-01-01

Abstract Background: Tamoxifen is the most widely used drug for treating patients with estrogen receptor-sensitive breast cancer. There is evidence that breast cancer patients treated with tamoxifen exhibit cognitive dysfunction. However, the underlying neural mechanism remains unclear. The present study aimed to investigate the neural mechanisms underlying working memory deficits in combination with functional connectivity changes in premenopausal women with breast cancer who received long-term tamoxifen treatment. Methods: A total of 31 premenopausal women with breast cancer who received tamoxifen and 32 matched healthy control participants were included. The participants completed n-back tasks and underwent resting-state functional magnetic resonance imaging, which measure working memory performance and brain functional connectivity, respectively. A seed-based functional connectivity analysis within the whole brain was conducted, for which the dorsolateral prefrontal cortex was chosen as the seed region. Results: Our results indicated that the tamoxifen group had significant deficits in working memory and general executive function performance and significantly lower functional connectivity of the right dorsolateral prefrontal cortex with the right hippocampus compared with the healthy controls. There were no significant changes in functional connectivity in the left dorsolateral prefrontal cortex within the whole brain between the tamoxifen group and healthy controls. Moreover, significant correlations were found in the tamoxifen group between the functional connectivity strength of the dorsolateral prefrontal cortex with the right hippocampus and decreased working memory performance. Conclusion: This study demonstrates that the prefrontal cortex and hippocampus may be affected by tamoxifen treatment, supporting an antagonistic role of tamoxifen in the long-term treatment of breast cancer patients. PMID:28177081

MPLS for metropolitan area networks

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Tan, Nam-Kee

2004-01-01

METROPOLITAN AREA NETWORKS AND MPLSRequirements of Metropolitan Area Network ServicesMetropolitan Area Network OverviewThe Bandwidth DemandThe Metro Service Provider's Business ApproachesThe Emerging Metro Customer Expectations and NeedsSome Prevailing Metro Service OpportunitiesService Aspects and RequirementsRoles of MPLS in Metropolitan Area NetworksMPLS PrimerMPLS ApplicationsTRAFFIC ENGINEERING ASPECTS OF METROPOLITAN AREA NETWORKSTraffic Engineering ConceptsNetwork CongestionHyper Aggregation ProblemEasing CongestionNetwork ControlTactical versus Strategic Traffic EngineeringIP/ATM Overl

Mapping the Hierarchical Layout of the Structural Network of the Macaque Prefrontal Cortex

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Goulas, A.; Uylings, H.B.M.; Stiers, P.

2014-01-01

A consensus on the prefrontal cortex (PFC) holds that it is pivotal for flexible behavior and the integration of the cognitive, affective, and motivational domains. Certain models have been put forth and a dominant model postulates a hierarchical anterior-posterior gradient. The structural

Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

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Anders H. Andersen

2015-01-01

Full Text Available Parkinson’s disease (PD is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD patients. Participants included 18 ndPD patients (11 men, 7 women and 10 dPD patients (7 men, 3 women. Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN. DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

Visuomotor Binding in Older Adults

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Bloesch, Emily K.; Abrams, Richard A.

2010-01-01

Action integration is the process through which actions performed on a stimulus and perceptual aspects of the stimulus become bound as a unitary object. This process appears to be controlled by the dopaminergic system in the prefrontal cortex, an area that is known to decrease in volume and dopamine functioning in older adults. Although the…

Activation of type 4 dopaminergic receptors in the prelimbic area of medial prefrontal cortex is necessary for the expression of innate fear behavior.

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Vergara, Macarena D; Keller, Victor N; Fuentealba, José A; Gysling, Katia

2017-05-01

The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression. In fact, the mPFC is the brain region with the highest expression of D4R; however, the role of D4R in the expression of innate fear has not been fully elucidated. Therefore, the principal objective of this work was to evaluate the participation of mPFC D4R in the expression of innate fear. Rats were exposed to the elevated plus-maze (EPM) and to the cat odor paradigm after the intra PL injection of L-745,870, selective D4R antagonist, to measure the expression of fear-related behaviors. Intra PL injection of L-745,870 increased the time spent in the EPM open arms and decreased freezing behavior in the cat odor paradigm. Our results also showed that D4R is expressed in GABAergic and pyramidal neurons in the PL region of PFC. Thus, D4R antagonism in the PL decreases the expression of innate fear-behavior indicating that the activation of D4R in the PL is necessary for the expression of innate fear-behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Food seeking in spite of harmful consequences is under prefrontal cortical noradrenergic control

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Patrono Enrico

2010-02-01

Full Text Available Abstract Background Eating disorders are multifactorial psychiatric disorders. Chronic stressful experiences and caloric restriction are the most powerful triggers of eating disorders in human and animals. Although compulsive behavior is considered to characterize pathological excessive food intake, to our knowledge, no evidence has been reported of continued food seeking/intake despite its possible harmful consequences, an index of compulsive behavior. Brain monoamine transmission is considered to have a key role in vulnerability to eating disorders, and norepinephrine in medial prefrontal cortex has been shown to be critical for food-related motivated behavior. Here, using a new paradigm of conditioned suppression, we investigated whether the ability of a foot-shock-paired conditioned stimulus to suppress chocolate-seeking behavior was reversed by previous exposure to a food restriction experience, thus modeling food seeking in spite of harmful consequences in mice. Moreover, we assessed the effects of selective norepinephrine inactivation in medial prefrontal cortex on conditioned suppression test in stressed and caloric restricted mice. Results While Control (non food deprived animals showed a profound conditioned suppression of chocolate seeking during presentation of conditioned stimulus, previously food restricted animals showed food seeking/intake despite its possible harmful consequences. Moreover, food seeking in spite of harmful consequences was prevented by selective norepinephrine inactivation, thus showing that prefrontal cortical norepinephrine is critical also for maladaptive food-related behavior. Conclusions These findings indicate that adaptive food seeking/intake can be transformed into maladaptive behaviors and point to "top-down" influence on eating disturbances and to new targets for therapy of aberrant eating behaviors.

Prefrontal Cortical GABA Modulation of Spatial Reference and Working Memory

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Auger, Meagan L.; Floresco, Stan B.

2014-01-01

Background: Dysfunction in prefrontal cortex (PFC) GABA transmission has been proposed to contribute to cognitive dysfunction in schizophrenia, yet how this system regulates different cognitive and mnemonic functions remains unclear. Methods: We assessed the effects of pharmacological reduction of GABAA signaling in the medial PFC of rats on spatial reference/working memory using different versions of the radial-arm maze task. We used a massed-trials procedure to probe how PFC GABA regulates ...

Noradrenergic Action in Prefrontal Cortex in the Late Stage of Memory Consolidation

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Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

2004-01-01

These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory…

The Medial Prefrontal Cortex Is Critical for Memory Retrieval and Resolving Interference

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Peters, Gregory J.; David, Christopher N.; Marcus, Madison D.; Smith, David M.

2013-01-01

The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC…

[Neuroanatomy of the Parietal Association Areas].

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Kobayashi, Yasushi

2016-11-01

The parietal association cortex comprises the superior and inferior parietal lobules, the precuneus and the cortices in the intraparietal, parietooccipital and lunate sulci. By processing somatic, visual, acoustic and vestibular sensory information, the parietal association cortex plays a pivotal role in spatial cognition and motor control of the eyes and the extremities. Sensory information from the primary and secondary somatosensory areas enters the superior parietal lobule and is transferred to the inferior parietal lobule. Visual information is processed through the dorsal visual pathway and it reaches the inferior parietal lobule, the intraparietal sulcus and the precuneus. Acoustic information is transferred posteriorly from the primary acoustic area, and it reaches the posterior region of the inferior parietal lobule. The areas in the intraparietal sulcus project to the premotor area, the frontal eye fields, and the prefrontal area. These areas are involved in the control of ocular movements, reaching and grasping of the upper extremities, and spatial working memory. The posterior region of the inferior parietal lobule and the precuneus both project either directly, or indirectly via the posterior cingulate gyrus, to the parahippocampal and entorhinal cortices. Both these areas are strongly associated with hippocampal functions for long-term memory formation.

Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders

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Qi, Xin-Rui; Zhao, Juan; Liu, Ji; Fang, Hui; Swaab, Dick F; Zhou, Jiang-Ning

The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly

SELECTED ASPECTS OF THE IMPLEMENTATION OF ACTIVE MARKETING CAMPAIGN TO RAISE AWARENESS AND PROMOTE PUBLIC TRANSPORT SERVICES IN RURAL AREAS

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Katarzyna NOSAL

2016-09-01

Full Text Available The article presents selected aspects of the implementation of the EU’s SmartMove project, which aims to promote feeder public transport systems in rural areas through the implementation of an active marketing campaign (AMC. Campaigns of this type are connected with providing general and personalized information concerning the functioning of public transport services. In the article, characteristics of one of the implementation areas of the project are presented, namely, the Liszki district near Cracow. Transport services were also evaluated. In addition, selected results are presented from a survey that was conducted among residents of the area from the point of view of the implementation of the AMC. The results concerned data about the means of transport that were currently used for travelling, the knowledge of bus services, the reasons for their use and the factors that might encourage residents to use public transport

Enhanced pain expectation in migraine: EEG-based evidence for impaired prefrontal function.

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Lev, Rina; Granovsky, Yelena; Yarnitsky, David

2013-01-01

Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9 μV) and unchanged ones in MOAs (1.1 μV) but not in controls (decrease of 5 μV). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5 μV and 4.4 μV, respectively) compared with controls (decrease of 0.2 μV). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P < .05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P < .05) and concern of upcoming migraine attacks (P < .05) in MWAs, and with frequency of migraine attacks in MOAs (P < .05). Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks. © 2012 American Headache Society.

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

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Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

2015-01-01

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of Hemodynamic Responses in the Prefrontal Cortex According to Differences in Self-Efficacy.

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Hirao, Kazuki

2017-07-01

Although self-efficacy has been used extensively in the field of nursing (e.g., as an outcome measure of nursing interventions), its underlying nature is poorly understood. Investigation of the relationship between self-efficacy and brain activation will help explain the fundamental nature of self-efficacy. In this study, we compared prefrontal activation measured with near-infrared spectroscopy (NIRS) across 89 undergraduate students categorized into three groups based on their General Self-Efficacy Scale scores: low self-efficacy ( n = 59), moderate self-efficacy ( n = 17), and high self-efficacy ( n = 13). Changes in the hemoglobin levels of the prefrontal cortex (PFC) during a verbal fluency task were assessed using two-channel NIRS. Significant differences in the oxygenated hemoglobin (oxy-Hb) level of the left PFC (LPFC) were observed via analysis of variance. Post hoc Tukey's test showed a significant difference only between low self-efficacy and moderate self-efficacy groups. We found a medium between-group effect size in the moderate self-efficacy group versus the low self-efficacy group for the changes in oxy-Hb levels of the LPFC ( d = .78; 95% confidence interval for effect size [0.22, 1.33]). No significant between-group differences were observed with respect to changes in the oxy-Hb in the right PFC. The results indicate less left prefrontal activation in the low self-efficacy group than in the moderate self-efficacy group. These findings provide evidence to support the fundamental nature of self-efficacy.

Fascioliasis hepatis - computed tomography aspects

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Goebel, N.; Markwalder, K.; Siegenthaler, W.

1984-12-01

In a patient with liver fascioliasis (already excreting eggs with the faeces) a CT scan of the liver showed after i.v. contrast injection a relatively characteristic aspect with multiple, small, hypodense areas, partly in formations of bunches of grapes, partly in a street-like arrangement towards the portal vein - bile duct - areas. 9 months later the hypodense lesions had markedly decreased.

Efficiency of the Prefrontal Cortex during Working Memory in Attention-Deficit/Hyperactivity Disorder

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Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

2007-01-01

Objective: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical(PFC) activation compared to age-matched control participants. This pattern may reflect…

Nicotinic acetylcholine receptor β2-subunits in the medial prefrontal cortex control attention

NARCIS (Netherlands)

Guillem, K.; Bloem, B.; Poorthuis, R.B.; Loos, M.; Smit, A.B.; Maskos, U.; Spijker, S.; Mansvelder, H.D.

2011-01-01

More than one-third of all people are estimated to experience mild to severe cognitive impairment as they age. Acetylcholine (ACh) levels in the brain diminish with aging, and nicotinic ACh receptor (nAChR) stimulation is known to enhance cognitive performance. The prefrontal cortex (PFC) is

Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder

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Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

2012-01-01

Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

Atypical prefrontal cortical responses to joint/non-joint attention in children with autism spectrum disorder (ASD): A functional near-infrared spectroscopy study

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Zhu, Huilin; Li, Jun; Fan, Yuebo; Li, Xinge; Huang, Dan; He, Sailing

2015-01-01

Autism spectrum disorder (ASD) is a neuro-developmental disorder, characterized by impairments in one’s capacity for joint attention. In this study, functional near-infrared spectroscopy (fNIRS) was applied to study the differences in activation and functional connectivity in the prefrontal cortex between children with autism spectrum disorder (ASD) and typically developing (TD) children. 21 ASD and 20 TD children were recruited to perform joint and non-joint attention tasks. Compared with TD children, children with ASD showed reduced activation and atypical functional connectivity pattern in the prefrontal cortex during joint attention. The atypical development of left prefrontal cortex might play an important role in social cognition defects of children with ASD. PMID:25798296

Prefrontal-hippocampal-fusiform activity during encoding predicts intraindividual differences in free recall ability: an event-related functional-anatomic MRI study.

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Dickerson, B C; Miller, S L; Greve, D N; Dale, A M; Albert, M S; Schacter, D L; Sperling, R A

2007-01-01

The ability to spontaneously recall recently learned information is a fundamental mnemonic activity of daily life, but has received little study using functional neuroimaging. We developed a functional MRI (fMRI) paradigm to study regional brain activity during encoding that predicts free recall. In this event-related fMRI study, ten lists of fourteen pictures of common objects were shown to healthy young individuals and regional brain activity during encoding was analyzed based on subsequent free recall performance. Free recall of items was predicted by activity during encoding in hippocampal, fusiform, and inferior prefrontal cortical regions. Within-subject variance in free recall performance for the ten lists was predicted by a linear combination of condition-specific inferior prefrontal, hippocampal, and fusiform activity. Recall performance was better for lists in which prefrontal activity was greater for all items of the list and hippocampal and fusiform activity were greater specifically for items that were recalled from the list. Thus, the activity of medial temporal, fusiform, and prefrontal brain regions during the learning of new information is important for the subsequent free recall of this information. These fronto-temporal brain regions act together as a large-scale memory-related network, the components of which make distinct yet interacting contributions during encoding that predict subsequent successful free recall performance.

The Limbic-Prefrontal Network Modulated by Electroacupuncture at CV4 and CV12

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Jiliang Fang

2012-01-01

Full Text Available fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture's modulation effects on brain functional networks by electroacupuncture (EA at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4 and Zhongwan (CV12 were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation.

Integration of auditory and visual communication information in the primate ventrolateral prefrontal cortex.

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Sugihara, Tadashi; Diltz, Mark D; Averbeck, Bruno B; Romanski, Lizabeth M

2006-10-25

The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O'Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication.

Functional connectivity in the prefrontal cortex measured by near-infrared spectroscopy during ultrarapid object recognition

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Medvedev, Andrei V.; Kainerstorfer, Jana M.; Borisov, Sergey V.; Vanmeter, John

2011-01-01

Near-infrared spectroscopy (NIRS) is a developing technology for low-cost noninvasive functional brain imaging. With multichannel optical instruments, it becomes possible to measure not only local changes in hemoglobin concentrations but also temporal correlations of those changes in different brain regions which gives an optical analog of functional connectivity traditionally measured by fMRI. We recorded hemodynamic activity during the Go-NoGo task from 11 right-handed subjects with probes placed bilaterally over prefrontal areas. Subjects were detecting animals as targets in natural scenes pressing a mouse button. Data were low-pass filtered right versus left hemisphere. Intra- and interhemispheric functional connectivity was also significantly stronger during the task compared to baseline. Functional connectivity between the inferior and the middle frontal regions was significantly stronger in the right hemisphere. Our results demonstrate that optical methods can be used to detect transient changes in functional connectivity during rapid cognitive processes.

The Blockade of Glutamate N-methyl-D-aspartate Receptors into the Prelimbic of Prefrontal Cortex Decreases Morphine-induced Conditioned Place Preference in Rat

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Samad Javadi

2017-12-01

Full Text Available BACKGROUND: The prelimbic area (PL of the prefrontal cortex is susceptible to abnormal developmental stimuli that raises the risk of addiction. Glutamate receptors play a key role in opiate reinforcement and reward functions in this area. Therefore, we examined the effect of the DL-2-amino-5-phosphonopentanoic acid (AP5, as N-methyl-D-aspartate (NMDA receptor antagonist into the PL on the phases of conditioned place preference (CPP induced by morphine. METHODS: Male Wistar rats were divided into 12 groups (3 surgical groups for each dose of morphine in any phase of CPP and anaesthetized with chloral hydrate. Cannula was implanted into the PL and the AP5 was injected into this area and morphine-induced CPP was investigated. Data were processed with the commercially available SPSS 22 software using one-way ANOVA and Tukey's test. p<0.05 were considered statistically significant. RESULTS: Our findings indicated, morphine in doses of 2.5 to 10 mg/kg induced CPP. Microinjection of various doses of the AP5 into the PL before the administration of the effective dose of morphine significantly reduced place preference in the acquisition and the expression phases of the CPP test compared to the sham group (p<0.001. In another set of our experiments was seen that, different doses of the AP5 with the ineffective dose of morphine only reduced the expression phase of the CPP (p<0.001 while, produced neither preference nor aversion effect on the acquisition phase (p=0.147. CONCLUSION: It seems that the glutamate NMDA receptors in the PL through memory formation and morphine-related reward signals play a critical role in addiction process during morphine-induced CPP. KEYWORDS: N-methyl-aspartate, morphine, glutamate receptor, prefrontal cortex, reward

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

Parameter-Based Evaluation of Attentional Impairments in Schizophrenia and Their Modulation by Prefrontal Transcranial Direct Current Stimulation

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Nadine Gögler

2017-11-01

Full Text Available BackgroundAttentional dysfunctions constitute core cognitive symptoms in schizophrenia, but the precise underlying neurocognitive mechanisms remain to be elucidated.MethodsIn this randomized, double-blind, sham-controlled study, we applied, for the first time, a theoretically grounded modeling approach based on Bundesen’s Theory of Visual Attention (TVA to (i identify specific visual attentional parameters affected in schizophrenia and (ii assess, as a proof of concept, the potential of single-dose anodal transcranial direct current stimulation (tDCS; 20 min, 2 mA to the left dorsolateral prefrontal cortex to modulate these attentional parameters. To that end, attentional parameters were measured before (baseline, immediately after, and 24 h after the tDCS intervention in 20 schizophrenia patients and 20 healthy controls.ResultsAt baseline, analyses revealed significantly reduced visual processing speed and visual short-term memory storage capacity in schizophrenia. A significant stimulation condition × time point interaction in the schizophrenia patient group indicated improved processing speed at the follow-up session only in the sham condition (a practice effect, whereas performance remained stable across the three time points in patients receiving verum stimulation. In healthy controls, anodal tDCS did not result in a significant change in attentional performance.ConclusionWith regard to question (i above, these findings are indicative of a processing speed and short-term memory deficit as primary sources of attentional deficits in schizophrenia. With regard to question (ii, the efficacy of single-dose anodal tDCS for improving (speed aspects of visual cognition, it appears that prefrontal tDCS (at the settings used in the present study, rather than ameliorating the processing speed deficit in schizophrenia, actually may interfere with practice-dependent improvements in the rate of visual information uptake. Such potentially

A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation.

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McKee, Sherry A; Potenza, Marc N; Kober, Hedy; Sofuoglu, Mehmet; Arnsten, Amy F T; Picciotto, Marina R; Weinberger, Andrea H; Ashare, Rebecca; Sinha, Rajita

2015-03-01

Stress and prefrontal cognitive dysfunction have key roles in driving smoking; however, there are no therapeutics for smoking cessation that attenuate the effects of stress on smoking and enhance cognition. Central noradrenergic pathways are involved in stress-induced reinstatement to nicotine and in the prefrontal executive control of adaptive behaviors. We used a novel translational approach employing a validated laboratory analogue of stress-precipitated smoking, functional magnetic resonance imaging (fMRI), and a proof-of-concept treatment period to evaluate whether the noradrenergic α2a agonist guanfacine (3 mg/day) versus placebo (0 mg/day) reduced stress-precipitated smoking in the laboratory, altered cortico-striatal activation during the Stroop cognitive-control task, and reduced smoking following a quit attempt. In nicotine-deprived smokers (n=33), stress versus a neutral condition significantly decreased the latency to smoke, and increased tobacco craving, ad-libitum smoking, and systolic blood pressure in placebo-treated subjects, and these effects were absent or reduced in guanfacine-treated subjects. Following stress, placebo-treated subjects demonstrated decreased cortisol levels whereas guanfacine-treated subjects demonstrated increased levels. Guanfacine, compared with placebo, altered prefrontal activity during a cognitive-control task, and reduced cigarette use but did not increase complete abstinence during treatment. These preliminary laboratory, neuroimaging, and clinical outcome data were consistent and complementary and support further development of guanfacine for smoking cessation. © The Author(s) 2014.

Prefrontal cognitive ability, intelligence, Big Five personality, and the prediction of advanced academic and workplace performance.

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Higgins, Daniel M; Peterson, Jordan B; Pihl, Robert O; Lee, Alice G M

2007-08-01

Studies 1 and 2 assessed performance on a battery of dorsolateral prefrontal cognitive ability (D-PFCA) tests, personality, psychometric intelligence, and academic performance (AP) in 2 undergraduate samples. In Studies 1 and 2, AP was correlated with D-PFCA (r=.37, ppersonality. Studies 3 and 4 assessed D-PFCA, personality, and workplace performance among (a) managerial-administrative workers and (b) factory floor workers at a manufacturing company. Prefrontal cognitive ability correlated with supervisor ratings of manager performance at values of r ranging from .42 to .57 (ps<.001), depending on experience, and with factory floor performance at pr=.21 (p=.02), after controlling for experience, age, and education. Conscientiousness correlated with factory floor performance at r=.23.

Decreased regional cerebral glucose metabolism in the prefrontal regions in adults' with internet game addiction

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Park, Hyun Soo; Bang, Soong Ae; Yoon, Eun Jin; Cho, Sang Soo; Kim, Sang Hee; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2007-07-01

Internet Game Addiction (IGA) is known to be associated with poor decision-making and diminished impulse control; however, the underlying neural substrates of IGA have not been identified. To investigate the neural substrates of IGA, we compared regional cerebral glucose metabolism between adults with and without IGA, primarily in the prefrontal brain regions, which have been implicated in inhibitory control. We studied 10 right-handed participants (5 controls: male, 23.8{+-}0.75 y, 5 IGAs: male, 22.6{+-}2.42 y) with FDG PET. A standardized questionnaire was used to assess the severity of IGA. Before scanning, all subjects carried out a computerized version of the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), as measures of behavioral inhibitory control. Statistical Parametric Mapping 2 (SPM2) was used to analyze differences in regional brain glucose metabolism between adults with and without IGA. Consistent with our predictions, compared to controls, significant reductions in FDG uptake in individuals with IGA were found in the bilateral orbitofrontal gyrus (BA 11, 47), bilateral inferior frontal gyrus (BA 44, 48), cingulate cortex (BA 24), and bilateral supplementary motor area (SMA) (BA 6); whereas increases were found in the bilateral hippocampus. Correlation analyses within the IGA group further showed that the level of glucose metabolism in the right orbitofrontal gyrus was marginally positively correlated with task scores in BART. Our results showed that IGA is associated with reduced glucose metabolism in the prefrontal regions involved in inhibitory control. This finding highlights dysfunctional inhibitory brain systems in individuals with IGA and offers implications for the development for therapeutic paradigms for IGA.

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.

Personality disorder symptomatology is associated with anomalies in striatal and prefrontal morphology

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Doris E Payer

2015-08-01

Full Text Available Personality disorder symptomatology (PD-Sx can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness / surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects. Subjects reporting PD-Sx were then grouped into symptom-based clusters: N=20 into Cluster B (reporting Antisocial, Borderline, Histrionic, or Narcissistic PD-Sx and N=28 into Cluster C (reporting Obsessive-Compulsive, Avoidant, or Dependent PD-Sx; N=11 subjects reported PD-Sx from both clusters, and none reported Cluster A (Paranoid, Schizoid, or Schizotypal PD-Sx. Compared to control, Cluster C PD-Sx was associated with greater striatal surface area localized to the caudate tail, smaller ventral striatum volumes, and greater cortical thickness in right prefrontal cortex. Both Cluster B and C PD-Sx groups also showed trends toward greater posterior caudate volumes and orbitofrontal surface area anomalies, but these findings did not survive correction for multiple comparisons. The results point to morphological abnormalities that could contribute to Cluster C PD-Sx. In addition, the observations parallel those in substance use disorders, pointing to the importance of considering PD-Sx when interpreting findings in often-comorbid psychiatric disorders.

Theory of mind difficulties in patients with alcohol dependence: beyond the prefrontal cortex dysfunction hypothesis.

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Maurage, François; de Timary, Philippe; Tecco, Juan Martin; Lechantre, Stéphane; Samson, Dana

2015-06-01

Previous studies have shown that alcohol-dependent (AD) individuals have difficulties inferring other people's emotion, understanding humor, and detecting a faux pas. This study aimed at further understanding the nature of such "Theory of Mind" (ToM) difficulties. A total of 34 recently detoxified AD and 34 paired controls were compared based on 2 nonverbal and video-based false belief tasks. These tasks were designed to identify 3 different types of deficits: (i) a deficit in dealing with the general task demands, (ii) a selective deficit in self-perspective inhibition, and (iii) a deficit in tracking the other person's mental state. (i) and (ii) are compatible with the hypothesis of a prefrontal cortex dysfunction being at the origin of AD individuals' social difficulties, while (iii) would suggest the possible contribution of a dysfunction of the temporo-parietal junction in explaining the social difficulties. Group analyses highlighted that AD individuals performed worse on the 2 false belief tasks than controls. Individual analyses showed, however, that just under half of the AD individuals were impaired compared to controls. Moreover, most of the AD individuals who were impaired showed a deficit in tracking the other person's belief. This deficit was linked to disease-related factors such as illness duration, average alcohol consumption, and craving but not to general reasoning abilities, depression, anxiety, or demographic variables. Just under half of the AD individuals tested showed a ToM deficit, and in most cases, the deficit concerned the tracking of other people's mental states. Such a type of deficit has previously been associated with lesions to the temporo-parietal brain areas, indicating that a prefrontal cortex dysfunction may not be the sole origin of the social cognition deficits observed in alcohol dependence. Copyright © 2015 by the Research Society on Alcoholism.

Distinct regions of prefrontal cortex are associated with the controlled retrieval and selection of social information.

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Satpute, Ajay B; Badre, David; Ochsner, Kevin N

2014-05-01

Research in social neuroscience has uncovered a social knowledge network that is particularly attuned to making social judgments. However, the processes that are being performed by both regions within this network and those outside of this network that are nevertheless engaged in the service of making a social judgment remain unclear. To help address this, we drew upon research in semantic memory, which suggests that making a semantic judgment engages 2 distinct control processes: A controlled retrieval process, which aids in bringing goal-relevant information to mind from long-term stores, and a selection process, which aids in selecting the information that is goal-relevant from the information retrieved. In a neuroimaging study, we investigated whether controlled retrieval and selection for social information engage distinct portions of both the social knowledge network and regions outside this network. Controlled retrieval for social information engaged an anterior ventrolateral portion of the prefrontal cortex, whereas selection engaged both the dorsomedial prefrontal cortex and temporoparietal junction within the social knowledge network. These results suggest that the social knowledge network may be more involved with the selection of social information than the controlled retrieval of it and incorporates lateral prefrontal regions in accessing memory for making social judgments.

Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

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Glen eAcosta

2012-01-01

Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

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Fan, Chunling; Zhang, Mengqi; Shang, Lei; Cynthia, Ngobe Akume; Li, Zhi; Yang, Zhenyu; Chen, Dan; Huang, Jufang; Xiong, Kun

2014-01-01

Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell proliferation), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs. PMID:25206818

Fascioliasis hepatis - computed tomography aspects

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Goebel, N.; Markwalder, K.; Siegenthaler, W.; Zurich Univ.

1984-01-01

In a patient with liver fascioliasis (already excreting eggs with the faeces) a CT scan of the liver showed after i.v. contrast injection a relatively characteristic aspect with multiple, small, hypodense areas, partly in formations of bunches of grapes, partly in a street-like arrangement towards the portal vein - bile duct - areas. 9 months later the hypodense lesions had markedly decreased. (orig.) [de