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Sample records for prefrontal cortex support

  1. Multiple component networks support working memory in prefrontal cortex.

    PubMed

    Markowitz, David A; Curtis, Clayton E; Pesaran, Bijan

    2015-09-01

    Lateral prefrontal cortex (PFC) is regarded as the hub of the brain's working memory (WM) system, but it remains unclear whether WM is supported by a single distributed network or multiple specialized network components in this region. To investigate this problem, we recorded from neurons in PFC while monkeys made delayed eye movements guided by memory or vision. We show that neuronal responses during these tasks map to three anatomically specific modes of persistent activity. The first two modes encode early and late forms of information storage, whereas the third mode encodes response preparation. Neurons that reflect these modes are concentrated at different anatomical locations in PFC and exhibit distinct patterns of coordinated firing rates and spike timing during WM, consistent with distinct networks. These findings support multiple component models of WM and consequently predict distinct failures that could contribute to neurologic dysfunction. PMID:26283366

  2. Medial prefrontal cortex supports source memory for self-referenced materials in young and older adults

    PubMed Central

    Leshikar, Eric D.; Duarte, Audrey

    2013-01-01

    Behavioral evidence suggests that young and older adults show a benefit in source memory accuracy when processing materials in reference to the self. In the young, activity within the medial prefrontal cortex supports this source memory benefit at study. This investigation examined whether the same neural regions support this memory benefit in both age groups. Using fMRI, participants were scanned while studying and retrieving pictures of objects paired with one of three scenes (source) under self-reference and other-reference conditions. At the time of study, half of the items were presented once and half twice, allowing us to match behavioral performance between groups. Both groups showed equivalent source accuracy benefit for objects encoded self-referentially. Activity in the left dorsal medial prefrontal cortex supported subsequent source memory in both age groups for the self-referenced relative to the other-referenced items. At the time of test, source accuracy for both self- and other-referenced items was supported by a network of regions including the precuneus in both age groups. At both study and test, little in the way of age-differences emerged, suggesting that when matched on behavioral performance young and older adults engage similar regions in support of source memory when processing materials in reference to the self; however, when performance was not matched, age differences in functional recruitment were prevalent. These results suggest that by capitalizing on preserved processes (self-referential encoding), older adults can show improvement in memory for source details which typically are not well remembered relative to the young. PMID:23904335

  3. MRI volumetry of prefrontal cortex

    NASA Astrophysics Data System (ADS)

    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 prefrontal cortex boundaries on 3D images was critical to obtaining accurate measurements. MR prefrontal cortex 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.

  4. Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

    PubMed Central

    Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot; Wulff, Peer

    2015-01-01

    Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements. PMID:26608841

  5. Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex.

    PubMed

    Barredo, Jennifer; Verstynen, Timothy D; Badre, David

    2016-09-01

    Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC [inferior frontal gyrus (IFG) pars orbitalis] functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (IFG pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with postretrieval control processes. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular-resolution diffusion spectrum imaging and functional connectivity analysis in unanesthetized humans to address whether the organization of white matter connectivity differs between subregions of VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Although several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the midfrontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of VLPFC support prior functional distinctions among these regions observed in task-based and functional connectivity fMRI studies. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general. PMID:27281745

  6. Mapping Prefrontal Cortex Functions in Human Infancy

    ERIC Educational Resources Information Center

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  7. Inputs to prefrontal cortex support visual recognition in the aging brain

    PubMed Central

    Gilbert, Jessica R.; Moran, Rosalyn J.

    2016-01-01

    Predictive coding models of brain function propose that top-down cortical signals promote efficient neural codes by carrying predictions of upcoming sensory events. We hypothesized that older brains would employ these codes more prominently given their longer repertoire of sensory experience. We measured the connectivity underlying stimulus-evoked responses in cortical visual networks using electroencephalography and dynamic causal modeling and found that in young adults with reported normal or corrected-to-normal vision, signals propagated from early visual regions and reverberated along reciprocal connections to temporal, parietal and frontal cortices, while in contrast, the network was driven by both early visual and prefrontal inputs in older adults with reported normal or corrected-to-normal vision. Previously thought of as exceptions to the rule of bottom-up signal propagation, our results demonstrate a prominent role for prefrontal inputs in driving vision in aged brains in line with lifespan-dependent predictive neural codes. PMID:27550752

  8. Inputs to prefrontal cortex support visual recognition in the aging brain.

    PubMed

    Gilbert, Jessica R; Moran, Rosalyn J

    2016-01-01

    Predictive coding models of brain function propose that top-down cortical signals promote efficient neural codes by carrying predictions of upcoming sensory events. We hypothesized that older brains would employ these codes more prominently given their longer repertoire of sensory experience. We measured the connectivity underlying stimulus-evoked responses in cortical visual networks using electroencephalography and dynamic causal modeling and found that in young adults with reported normal or corrected-to-normal vision, signals propagated from early visual regions and reverberated along reciprocal connections to temporal, parietal and frontal cortices, while in contrast, the network was driven by both early visual and prefrontal inputs in older adults with reported normal or corrected-to-normal vision. Previously thought of as exceptions to the rule of bottom-up signal propagation, our results demonstrate a prominent role for prefrontal inputs in driving vision in aged brains in line with lifespan-dependent predictive neural codes. PMID:27550752

  9. Auditory connections and functions of prefrontal cortex

    PubMed Central

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

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

  10. Finding prefrontal cortex in the rat.

    PubMed

    Leonard, Christiana M

    2016-08-15

    The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID:26867704

  11. Dissociation in prefrontal cortex of affective and attentional shifts.

    PubMed

    Dias, R; Robbins, T W; Roberts, A C

    1996-03-01

    The prefrontal cortex is implicated in such human characteristics as volition, planning, abstract reasoning and affect. Frontal-lobe damage can cause disinhibition such that the behaviour of a subject is guided by previously acquired responses that are inappropriate to the current situation. Here we demonstrate that disinhibition, or a loss of inhibitory control, can be selective for particular cognitive functions and that different regions of the prefrontal cortex provide inhibitory control in different aspects of cognitive processing. Thus, whereas damage to the lateral prefrontal cortex (Brodmann's area 9) in monkeys causes a loss of inhibitory control in attentional selection, damage to the orbito-frontal cortex in monkeys causes a loss of inhibitory control in 'affective' processing, thereby impairing the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli. These findings not only support the view that the prefrontal cortex has multiple functions, but also provide evidence for the distribution of different cognitive functions within specific regions of prefrontal cortex. PMID:8598908

  12. Interplay of hippocampus and prefrontal cortex in memory

    PubMed Central

    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

  13. Developmental Outcomes after Early Prefrontal Cortex Damage

    ERIC Educational Resources Information Center

    Eslinger, Paul J.; Flaherty-Craig, Claire V.; Benton, Arthur L.

    2004-01-01

    The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical…

  14. Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

    ERIC Educational Resources Information Center

    Cruse, Damian; Wilding, Edward L.

    2009-01-01

    Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation--the right-frontal ERP old/new effect--which is thought to reflect activity in PFC. The functional…

  15. The role of prefrontal cortex in psychopathy

    PubMed Central

    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

  16. Revisiting the Role of the Prefrontal Cortex in the Pathophysiology of Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Halperin, Jeffrey M.; Schulz, Kurt P.

    2006-01-01

    Most neural models for the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) have centered on the prefrontal cortex and its interconnections with the striatum and other subcortical structures. However, research only partially supports these models, and they do not correspond with the development of the prefrontal cortex and its…

  17. Altered functional connectivity of the insular cortex across prefrontal networks in cocaine addiction.

    PubMed

    Cisler, Josh M; Elton, Amanda; Kennedy, Ashley P; Young, Jonathan; Smitherman, Sonet; Andrew James, George; Kilts, Clinton D

    2013-07-30

    Interoception is theorized to be an important process mediating substance use disorders, and the insular cortex is recognized as a core neural region supporting interoception. The purpose of this study was to compare the integration of the insular cortex into prefrontal-related resting-state networks between individuals with cocaine dependence and healthy controls. Participants comprised 41 patients with cocaine dependence and 19 controls who underwent a resting-state 3-T functional magnetic resonance imaging scan. Individuals with cocaine dependence demonstrated altered functional connectivity of the insular cortex, predominantly the right insular cortex, with all eight prefrontal-related resting-state networks identified through Independent Component Analysis (ICA). A conjunction analysis demonstrated that the right insular cortex was the neural region with the highest number of common group differences across the networks. There was no evidence that insular cortex connectivity commonly differed between groups for non-prefrontal-related networks. Further, seed-based functional connectivity analyses extended the network analyses and indicated that cocaine dependence was associated with greater connectivity of the right insula with the dorsomedial prefrontal cortex, inferior frontal gyrus, and bilateral dorsolateral prefrontal cortex. These data support the hypothesis that cocaine dependence is related to altered functional interactions of the insular cortex with prefrontal networks. The results suggest possible neural mechanisms by which the insular cortex and interoceptive information influence cognitive control and decision-making processes presumably mediated by prefrontal networks in the cocaine dependence process. PMID:23684980

  18. Discourse Production Following Injury to the Dorsolateral Prefrontal Cortex

    ERIC Educational Resources Information Center

    Coelho, Carl; Le, Karen; Mozeiko, Jennifer; Krueger, Frank; Grafman, Jordan

    2012-01-01

    Individuals with damage to the prefrontal cortex, and the dorsolateral prefrontal cortex (DLPFC) in particular, often demonstrate difficulties with the formulation of complex language not attributable to aphasia. The present study employed a discourse analysis procedure to characterize the language of individuals with left (L) or right (R) DLPFC…

  19. Medial Prefrontal Cortex Lesions Abolish Contextual Control of Competing Responses

    ERIC Educational Resources Information Center

    Haddon, J. E.; Killcross, A. S.

    2005-01-01

    There is much debate as to the extent and nature of functional specialization within the different subregions of the prefrontal cortex. The current study was undertaken to investigate the effect of damage to medial prefrontal cortex subregions in the rat. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in…

  20. Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

    PubMed

    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. PMID:24691392

  1. Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition

    PubMed Central

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

    2014-01-01

    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. PMID:24691392

  2. Divergent Plasticity of Prefrontal Cortex Networks

    PubMed Central

    Moghaddam, Bita; Homayoun, Houman

    2010-01-01

    The ‘executive’ regions of the prefrontal cortex (PFC) such as the dorsolateral PFC (dlPFC) and its rodent equivalent medial PFC (mPFC) are thought to respond in concert with the ‘limbic’ regions of the PFC such as the orbitofrontal (OFC) cortex to orchestrate behavior that is consistent with context and expected outcome. Both groups of regions have been implicated in behavioral abnormalities associated with addiction and psychiatric disorders, in particular, schizophrenia and mood disorders. Theories about the pathophysiology of these disorders, however, incorporate abnormalities in discrete PFC regions independently of each other or assume they are one and the same and, thus, bunch them under umbrella of ‘PFC dysfunction.’ Emerging data from animal studies suggest that mPFC and OFC neurons display opposing patterns of plasticity during associative learning and in response to repeated exposure to psychostimulants. These data corroborate clinical studies reporting different patterns of activation in OFC versus dlPFC in individuals with schizophrenia or addictive disorders. These suggest that concomitant but divergent engagement of discrete PFC regions is critical for learning stimulus-outcome associations, and the execution of goal-directed behavior that is based on these associations. An atypical interplay between these regions may lead to abnormally high or low salience assigned to stimuli, resulting in symptoms that are fundamental to many psychiatric and addictive disorders, including attentional deficits, improper affective response to stimuli, and inflexible or impulsive behavior. PMID:17912252

  3. Altered Functional Connectivity of the Insular Cortex across Prefrontal Networks in Cocaine Addiction

    PubMed Central

    Cisler, Josh M.; Elton, Amanda; Kennedy, Ashley P.; Young, Jonathan; Smitherman, Sonet; James, George Andrew; Kilts, Clinton D.

    2013-01-01

    Interoception is theorized to be an important process mediating substance use disorders, and the insular cortex is recognized as a core neural region supporting interoception. The purpose of this study was to compare the integration of the insular cortex into prefrontal-related resting-state networks between individuals with cocaine dependence and healthy controls. 41 participants with cocaine dependence and 19 control participants underwent a resting-state 3T fMRI scan. Individuals with cocaine dependence demonstrated altered functional connectivity of the insular cortex, predominantly the right insular cortex, with all eight prefrontal-related resting-state networks identified through Independent Component Analysis (ICA). A conjunction analysis demonstrated that the right insular cortex was the neural region with the highest number of common group differences across the networks. There was no evidence that insular cortex connectivity commonly differed between groups for non-prefrontal-related networks. Further, seed-based functional connectivity analyses extended the network analyses and indicated that cocaine dependence was associated with greater connectivity of the right insula with the dorsomedial PFC, inferior frontal gyrus, and bilateral dlPFC. These data support the hypothesis that cocaine dependence is related to altered functional interactions of the insular cortex with prefrontal networks. The results suggest possible neural mechanisms by which the insular cortex and interoceptive information influence cognitive control and decision-making processes presumably mediated by prefrontal networks in the cocaine dependence process. PMID:23684980

  4. Optogenetic dissection of medial prefrontal cortex circuitry

    PubMed Central

    Riga, Danai; Matos, Mariana R.; Glas, Annet; Smit, August B.; Spijker, Sabine; Van den Oever, Michel C.

    2014-01-01

    The medial prefrontal cortex (mPFC) is critically involved in numerous cognitive functions, including attention, inhibitory control, habit formation, working memory and long-term memory. Moreover, through its dense interconnectivity with subcortical regions (e.g., thalamus, striatum, amygdala and hippocampus), the mPFC is thought to exert top-down executive control over the processing of aversive and appetitive stimuli. Because the mPFC has been implicated in the processing of a wide range of cognitive and emotional stimuli, it is thought to function as a central hub in the brain circuitry mediating symptoms of psychiatric disorders. New optogenetics technology enables anatomical and functional dissection of mPFC circuitry with unprecedented spatial and temporal resolution. This provides important novel insights in the contribution of specific neuronal subpopulations and their connectivity to mPFC function in health and disease states. In this review, we present the current knowledge obtained with optogenetic methods concerning mPFC function and dysfunction and integrate this with findings from traditional intervention approaches used to investigate the mPFC circuitry in animal models of cognitive processing and psychiatric disorders. PMID:25538574

  5. The medial prefrontal cortex exhibits money illusion

    PubMed Central

    Weber, Bernd; Rangel, Antonio; Wibral, Matthias; Falk, Armin

    2009-01-01

    Behavioral economists have proposed that money illusion, which is a deviation from rationality in which individuals engage in nominal evaluation, can explain a wide range of important economic and social phenomena. This proposition stands in sharp contrast to the standard economic assumption of rationality that requires individuals to judge the value of money only on the basis of the bundle of goods that it can buy—its real value—and not on the basis of the actual amount of currency—its nominal value. We used fMRI to investigate whether the brain's reward circuitry exhibits money illusion. Subjects received prizes in 2 different experimental conditions that were identical in real economic terms, but differed in nominal terms. Thus, in the absence of money illusion there should be no differences in activation in reward-related brain areas. In contrast, we found that areas of the ventromedial prefrontal cortex (vmPFC), which have been previously associated with the processing of anticipatory and experienced rewards, and the valuation of goods, exhibited money illusion. We also found that the amount of money illusion exhibited by the vmPFC was correlated with the amount of money illusion exhibited in the evaluation of economic transactions. PMID:19307555

  6. Differential Effects of Insular and Ventromedial Prefrontal Cortex Lesions on Risky Decision-Making

    ERIC Educational Resources Information Center

    Clark, L.; Bechara, A.; Damasio, H.; Aitken, M. R. F.; Sahakian, B. J.; Robbins, T. W.

    2008-01-01

    The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear…

  7. Evidence for inhibitory deficits in the prefrontal cortex in schizophrenia

    PubMed Central

    Radhu, Natasha; Garcia Dominguez, Luis; Farzan, Faranak; Richter, Margaret A.; Semeralul, Mawahib O.; Chen, Robert; Fitzgerald, Paul B.

    2015-01-01

    Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the

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

    PubMed

    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. PMID:26115848

  9. Ventromedial prefrontal cortex, adding value to autobiographical memories.

    PubMed

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

    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 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. PMID:27338616

  10. Is the Medial Prefrontal Cortex Necessary for Theory of Mind?

    PubMed Central

    Otti, Alexander; Wohlschlaeger, Afra M.; Noll-Hussong, Michael

    2015-01-01

    Background Successful social interaction relies on the ability to attribute mental states to other people. Previous functional neuroimaging studies have shown that this process, described as Theory of Mind (ToM) or mentalization, is reliably associated with activation of the medial prefrontal cortex (mPFC). However, this study presents a novel and surprising finding that provides new insight into the role of the mPFC in mentalization tasks. Methodology/Principal Findings Twenty healthy individuals were recruited from a wide range of ages and social backgrounds. Participants underwent functional magnetic resonance imaging (fMRI) while viewing a well-established ToM visual paradigm involving moving triangles. Functional MRI data were analyzed using a classical general linear model. No activation was detected in the medial prefrontal cortex (mPFC) during movement patterns that typically elicit ToM. However, increased activity was observed in the right middle occipital gyrus, right temporoparietal junction (TPJ), left middle occipital gyrus and right inferior frontal gyrus. No correlation was found between participants’ age and BOLD response. Conclusions/Significance In contrast with previous neuroimaging research, our findings support the notion that mPFC function is not critical for reasoning about the mental states of others; furthermore, our data indicate that the right TPJ and right inferior frontal gyrus are able to perform mentalization without any contributions from the mPFC. PMID:26301900

  11. Ventromedial prefrontal cortex, adding value to autobiographical memories

    PubMed Central

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

    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 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. PMID:27338616

  12. Neurodynamics of the prefrontal cortex during conditional visuomotor associations.

    PubMed

    Loh, Marco; Pasupathy, Anitha; Miller, Earl K; Deco, Gustavo

    2008-03-01

    The prefrontal cortex is believed to be important for cognitive control, working memory, and learning. It is known to play an important role in the learning and execution of conditional visuomotor associations, a cognitive task in which stimuli have to be associated with actions by trial-and-error learning. In our modeling study, we sought to integrate several hypotheses on the function of the prefrontal cortex using a computational model, and compare the results to experimental data. We constructed a module of prefrontal cortex neurons exposed to two different inputs, which we envision to originate from the inferotemporal cortex and the basal ganglia. We found that working memory properties do not describe the dominant dynamics in the prefrontal cortex, but the activation seems to be transient, probably progressing along a pathway from sensory to motor areas. During the presentation of the cue, the dynamics of the prefrontal cortex is bistable, yielding a distinct activation for correct and error trails. We find that a linear change in network parameters relates to the changes in neural activity in consecutive correct trials during learning, which is important evidence for the underlying learning mechanisms. PMID:18004947

  13. Deficits in prospective memory following damage to the prefrontal cortex.

    PubMed

    Umeda, Satoshi; Kurosaki, Yoshiko; Terasawa, Yuri; Kato, Motoichiro; Miyahara, Yasuyuki

    2011-07-01

    Neuropsychological investigations of prospective memory (PM), representing memory of future intentions or plans, have evolved over the past two decades. The broadly accepted divisions involved in PM consist of a prospective memory component (PMC), a process for remembering to remember, and a retrospective memory component, a process for remembering the content of the intended action. Previous functional neuroimaging studies have provided some evidence that the rostral prefrontal cortex (BA10) is one of areas that is critical for prospective remembering. However, the question of whether damage to part of the prefrontal cortex affects attenuated performance for PMC remains unresolved. In this study, 74 participants with traumatic brain injury (TBI) including focal damage to frontal or temporal lobe areas were administered thirteen standard neuropsychological tests and the PM task. To identify influential areas contributing to PM performance, discriminant function analysis was conducted. The results indicated that the following three areas are highly contributory to PM performance: the right dorsolateral prefrontal cortex; the right ventromedial prefrontal cortex; and the left dorsomedial prefrontal cortex. Comparing differences in neuropsychological test scores showed that orientation scores were significantly higher in the greater PM performance group, suggesting that PMC represents an integrated memory function associated with awareness of current status. These data contribute to our understanding of the neural substrates and functional characteristics of the PMC. PMID:21477605

  14. A parametric relief signal in human ventrolateral prefrontal cortex.

    PubMed

    Fujiwara, Juri; Tobler, Philippe N; Taira, Masato; Iijima, Toshio; Tsutsui, Ken-Ichiro

    2009-02-01

    People experience relief whenever outcomes are better than they would have been, had an alternative course of action been chosen. Here we investigated the neuronal basis of relief with functional resonance imaging in a choice task in which the outcome of the chosen option and that of the unchosen option were revealed sequentially. We found parametric activation increases in anterior ventrolateral prefrontal cortex with increasing relief (chosen outcomes better than unchosen outcomes). Conversely, anterior ventrolateral prefrontal activation was unrelated to the opposite of relief, increasing regret (chosen outcomes worse than unchosen outcomes). Furthermore, the anterior ventrolateral prefrontal activation was unrelated to primary gains and increased with relief irrespective of whether the chosen outcome was a loss or a gain. These results suggest that the anterior ventrolateral prefrontal cortex encodes a higher-order reward signal that lies at the core of current theories of emotion. PMID:18992349

  15. Abstract context representations in primate amygdala and prefrontal cortex

    PubMed Central

    Saez, A.; Rigotti, M.; Ostojic, S.; Fusi, S.; Salzman, C. D.

    2015-01-01

    Summary Neurons in prefrontal cortex (PFC) encode rules, goals and other abstract information thought to underlie cognitive, emotional, and behavioral flexibility. Here we show that the amygdala, a brain area traditionally thought to mediate emotions, also encodes abstract information that could underlie this flexibility. Monkeys performed a task in which stimulus-reinforcement contingencies varied between two sets of associations, each defining a context. Reinforcement prediction required identifying a stimulus and knowing the current context. Behavioral evidence indicated that monkeys utilized this information to perform inference and adjust their behavior. Neural representations in both amygdala and PFC reflected the linked sets of associations implicitly defining each context, a process requiring a level of abstraction characteristic of cognitive operations. Surprisingly, when errors were made, the context signal weakened substantially in the amygdala. These data emphasize the importance of maintaining abstract cognitive information in the amygdala to support flexible behavior. PMID:26291167

  16. Abstract Context Representations in Primate Amygdala and Prefrontal Cortex.

    PubMed

    Saez, A; Rigotti, M; Ostojic, S; Fusi, S; Salzman, C D

    2015-08-19

    Neurons in prefrontal cortex (PFC) encode rules, goals, and other abstract information thought to underlie cognitive, emotional, and behavioral flexibility. Here we show that the amygdala, a brain area traditionally thought to mediate emotions, also encodes abstract information that could underlie this flexibility. Monkeys performed a task in which stimulus-reinforcement contingencies varied between two sets of associations, each defining a context. Reinforcement prediction required identifying a stimulus and knowing the current context. Behavioral evidence indicated that monkeys utilized this information to perform inference and adjust their behavior. Neural representations in both amygdala and PFC reflected the linked sets of associations implicitly defining each context, a process requiring a level of abstraction characteristic of cognitive operations. Surprisingly, when errors were made, the context signal weakened substantially in the amygdala. These data emphasize the importance of maintaining abstract cognitive information in the amygdala to support flexible behavior. PMID:26291167

  17. Medial prefrontal cortex predicts internally driven strategy shifts

    PubMed Central

    Schuck, Nicolas W.; Gaschler, Robert; Wenke, Dorit; Heinzle, Jakob; Frensch, Peter A.; Haynes, John-Dylan; Reverberi, Carlo

    2015-01-01

    Summary Many daily behaviors require us to actively focus on the current task and ignore all other distractions. Yet, ignoring everything else might hinder the ability to discover new ways to achieve the same goal. Here, we studied the neural mechanisms that support the spontaneous change to better strategies while an established strategy is executed. Multivariate neuroimaging analysis showed that before the spontaneous change to an alternative strategy, medial prefrontal cortex (MPFC) encoded information that was irrelevant for the current strategy but necessary for the later strategy. Importantly, this neural effect was related to future behavioral changes: information encoding in MPFC was changed only in participants who eventually switched their strategy and started before the actual strategy change. This allowed us to predict spontaneous strategy shifts ahead of time. These findings suggest that MPFC might internally simulate alternative strategies and sheds new light on the organization of PFC. PMID:25819613

  18. Prefrontal Cortex Activity Related to Abstract Response Strategies

    PubMed Central

    Genovesio, Aldo; Brasted, Peter J.; Mitz, Andrew R.; Wise, Steven P.

    2005-01-01

    Overview In monkeys, foraging strategies depend not only on a context established by spatial or symbolic cues, but also on the relations among cues. Genovesio et al. recorded the activity of prefrontal cortex neurons while monkeys chose a strategy based on the relation between consecutive symbolic cues. For the same cues and actions, the monkeys also learned fixed responses to the same symbols. Many neurons had activity selective for a given strategy, others for whether the monkeys’ response choice depended on a symbol or the relation between symbols. These findings indicate that the primate prefrontal cortex contributes to implementing abstract strategies. PMID:16039571

  19. Development of Rostral Prefrontal Cortex and Cognitive and Behavioural Disorders

    ERIC Educational Resources Information Center

    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…

  20. Extinction Circuits for Fear and Addiction Overlap in Prefrontal Cortex

    ERIC Educational Resources Information Center

    Peters, Jamie; Kalivas, Peter W.; Quirk, Gregory J.

    2009-01-01

    Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is…

  1. Anterior prefrontal cortex inhibition impairs control over social emotional actions.

    PubMed

    Volman, Inge; Roelofs, Karin; Koch, Saskia; Verhagen, Lennart; Toni, Ivan

    2011-10-25

    When dealing with emotional situations, we often need to rapidly override automatic stimulus-response mappings and select an alternative course of action [1], for instance, when trying to manage, rather than avoid, another's aggressive behavior. The anterior prefrontal cortex (aPFC) has been linked to the control of these social emotional behaviors [2, 3]. We studied how this control is implemented by inhibiting the left aPFC with continuous theta burst stimulation (cTBS; [4]). The behavioral and cerebral consequences of this intervention were assessed with a task quantifying the control of social emotional actions and with concurrent measurements of brain perfusion. Inhibition of the aPFC led participants to commit more errors when they needed to select rule-driven responses overriding automatic action tendencies evoked by emotional faces. Concurrently, task-related perfusion decreased in bilateral aPFC and posterior parietal cortex and increased in amygdala and left fusiform face area. We infer that the aPFC controls social emotional behavior by upregulating regions involved in rule selection [5] and downregulating regions supporting the automatic evaluation of emotions [6]. These findings illustrate how exerting emotional control during social interactions requires the aPFC to coordinate rapid action selection processes, the detection of emotional conflicts, and the inhibition of emotionally-driven responses. PMID:22000109

  2. Social cognition in patients following surgery to the prefrontal cortex.

    PubMed

    Jenkins, Lisanne Michelle; Andrewes, David Gordon; Nicholas, Christian Luke; Drummond, Katharine Jann; Moffat, Bradford Armstrong; Phal, Pramit; Desmond, Patricia; Kessels, Roy Peter Caspar

    2014-12-30

    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 sought to investigate social cognition in patients with discrete, surgically circumscribed prefrontal lesions. Twenty-seven patients between 1 and 12 months post-neurosurgery were divided into groups based on Brodmann areas resected, determined by post-surgical magnetic resonance imaging. We hypothesised that patients with lesions to the VMPFC (n=5), anterior cingulate cortex (n=4), orbitofrontal cortex (n=7) and dorsolateral prefrontal cortex (DLPFC, n=11) would perform worse than a control group of 26 extra-cerebral neurosurgery patients on measures of dynamic facial emotion recognition, theory of mind (ToM) and empathy. Results indicated the VMPFC-lesioned group performed significantly worse than the control group on the facial emotion recognition task overall, and for fear specifically, and performed worse on the ToM measure. The DLPFC group also performed worse on the ToM and empathy measures, but DLPFC lesion location was not a predictor of performance in hierarchical multiple regressions that accounted for other variables, including the reduced estimated verbal IQ in this group. It was concluded that isolated orbital or medial prefrontal lesions are not sufficient to produce impairments in social cognition. This is the first study to demonstrate that it is the combination of lesions to both areas that affect social cognition, irrespective of lesion volume. While group sizes were similar to other comparable studies that included patients with discrete, surgically circumscribed lesions to the prefrontal cortex, future large, multi-site studies are needed to collect larger samples and confirm these results. PMID:25284626

  3. Architecture of Explanatory Inference in the Human Prefrontal Cortex

    PubMed Central

    Barbey, Aron K.; Patterson, Richard

    2011-01-01

    Causal reasoning is a ubiquitous feature of human cognition. We continuously seek to understand, at least implicitly and often explicitly, the causal scenarios in which we live, so that we may anticipate what will come next, plan a potential response and envision its outcome, decide among possible courses of action in light of their probable outcomes, make midstream adjustments in our goal-related activities as our situation changes, and so on. A considerable body of research shows that the lateral prefrontal cortex (PFC) is crucial for causal reasoning, but also that there are significant differences in the manner in which ventrolateral PFC, dorsolateral PFC, and anterolateral PFC support causal reasoning. We propose, on the basis of research on the evolution, architecture, and functional organization of the lateral PFC, a general framework for understanding its roles in the many and varied sorts of causal reasoning carried out by human beings. Specifically, the ventrolateral PFC supports the generation of basic causal explanations and inferences; dorsolateral PFC supports the evaluation of these scenarios in light of some given normative standard (e.g., of plausibility or correctness in light of real or imagined causal interventions); and anterolateral PFC supports explanation and inference at an even higher level of complexity, coordinating the processes of generation and evaluation with further cognitive processes, and especially with computations of hedonic value and emotional implications of possible behavioral scenarios – considerations that are often critical both for understanding situations causally and for deciding about our own courses of action. PMID:21845182

  4. Architecture of explanatory inference in the human prefrontal cortex.

    PubMed

    Barbey, Aron K; Patterson, Richard

    2011-01-01

    Causal reasoning is a ubiquitous feature of human cognition. We continuously seek to understand, at least implicitly and often explicitly, the causal scenarios in which we live, so that we may anticipate what will come next, plan a potential response and envision its outcome, decide among possible courses of action in light of their probable outcomes, make midstream adjustments in our goal-related activities as our situation changes, and so on. A considerable body of research shows that the lateral prefrontal cortex (PFC) is crucial for causal reasoning, but also that there are significant differences in the manner in which ventrolateral PFC, dorsolateral PFC, and anterolateral PFC support causal reasoning. We propose, on the basis of research on the evolution, architecture, and functional organization of the lateral PFC, a general framework for understanding its roles in the many and varied sorts of causal reasoning carried out by human beings. Specifically, the ventrolateral PFC supports the generation of basic causal explanations and inferences; dorsolateral PFC supports the evaluation of these scenarios in light of some given normative standard (e.g., of plausibility or correctness in light of real or imagined causal interventions); and anterolateral PFC supports explanation and inference at an even higher level of complexity, coordinating the processes of generation and evaluation with further cognitive processes, and especially with computations of hedonic value and emotional implications of possible behavioral scenarios - considerations that are often critical both for understanding situations causally and for deciding about our own courses of action. PMID:21845182

  5. A dorsolateral prefrontal cortex semi-automatic segmenter

    NASA Astrophysics Data System (ADS)

    Al-Hakim, Ramsey; Fallon, James; Nain, Delphine; Melonakos, John; Tannenbaum, Allen

    2006-03-01

    Structural, functional, and clinical studies in schizophrenia have, for several decades, consistently implicated dysfunction of the prefrontal cortex in the etiology of the disease. Functional and structural imaging studies, combined with clinical, psychometric, and genetic analyses in schizophrenia have confirmed the key roles played by the prefrontal cortex and closely linked "prefrontal system" structures such as the striatum, amygdala, mediodorsal thalamus, substantia nigra-ventral tegmental area, and anterior cingulate cortices. The nodal structure of the prefrontal system circuit is the dorsal lateral prefrontal cortex (DLPFC), or Brodmann area 46, which also appears to be the most commonly studied and cited brain area with respect to schizophrenia. 1, 2, 3, 4 In 1986, Weinberger et. al. tied cerebral blood flow in the DLPFC to schizophrenia.1 In 2001, Perlstein et. al. demonstrated that DLPFC activation is essential for working memory tasks commonly deficient in schizophrenia. 2 More recently, groups have linked morphological changes due to gene deletion and increased DLPFC glutamate concentration to schizophrenia. 3, 4 Despite the experimental and clinical focus on the DLPFC in structural and functional imaging, the variability of the location of this area, differences in opinion on exactly what constitutes DLPFC, and inherent difficulties in segmenting this highly convoluted cortical region have contributed to a lack of widely used standards for manual or semi-automated segmentation programs. Given these implications, we developed a semi-automatic tool to segment the DLPFC from brain MRI scans in a reproducible way to conduct further morphological and statistical studies. The segmenter is based on expert neuroanatomist rules (Fallon-Kindermann rules), inspired by cytoarchitectonic data and reconstructions presented by Rajkowska and Goldman-Rakic. 5 It is semi-automated to provide essential user interactivity. We present our results and provide details on

  6. Prefrontal Cortex and Social Cognition in Mouse and Man

    PubMed Central

    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

  7. Prefrontal Cortex and Social Cognition in Mouse and Man.

    PubMed

    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

  8. The hierarchical organization of the lateral prefrontal cortex

    PubMed Central

    Nee, Derek Evan; D'Esposito, Mark

    2016-01-01

    Higher-level cognition depends on the lateral prefrontal cortex (LPFC), but its functional organization has remained elusive. An influential proposal is that the LPFC is organized hierarchically whereby progressively rostral areas of the LPFC process/represent increasingly abstract information facilitating efficient and flexible cognition. However, support for this theory has been limited. Here, human fMRI data revealed rostral/caudal gradients of abstraction in the LPFC. Dynamic causal modeling revealed asymmetrical LPFC interactions indicative of hierarchical processing. Contrary to dominant assumptions, the relative strength of efferent versus afferent connections positioned mid LPFC as the apex of the hierarchy. Furthermore, cognitive demands induced connectivity modulations towards mid LPFC consistent with a role in integrating information for control operations. Moreover, the strengths of these dynamics were related to trait-measured higher-level cognitive ability. Collectively, these results suggest that the LPFC is hierarchically organized with the mid LPFC positioned to synthesize abstract and concrete information to control behavior. DOI: http://dx.doi.org/10.7554/eLife.12112.001 PMID:26999822

  9. Nature experience reduces rumination and subgenual prefrontal cortex activation

    PubMed Central

    Bratman, Gregory N.; Hamilton, J. Paul; Hahn, Kevin S.; Daily, Gretchen C.; Gross, James J.

    2015-01-01

    Urbanization has many benefits, but it also is associated with increased levels of mental illness, including depression. It has been suggested that decreased nature experience may help to explain the link between urbanization and mental illness. This suggestion is supported by a growing body of correlational and experimental evidence, which raises a further question: what mechanism(s) link decreased nature experience to the development of mental illness? One such mechanism might be the impact of nature exposure on rumination, a maladaptive pattern of self-referential thought that is associated with heightened risk for depression and other mental illnesses. We show in healthy participants that a brief nature experience, a 90-min walk in a natural setting, decreases both self-reported rumination and neural activity in the subgenual prefrontal cortex (sgPFC), whereas a 90-min walk in an urban setting has no such effects on self-reported rumination or neural activity. In other studies, the sgPFC has been associated with a self-focused behavioral withdrawal linked to rumination in both depressed and healthy individuals. This study reveals a pathway by which nature experience may improve mental well-being and suggests that accessible natural areas within urban contexts may be a critical resource for mental health in our rapidly urbanizing world. PMID:26124129

  10. The hierarchical organization of the lateral prefrontal cortex.

    PubMed

    Nee, Derek Evan; D'Esposito, Mark

    2016-01-01

    Higher-level cognition depends on the lateral prefrontal cortex (LPFC), but its functional organization has remained elusive. An influential proposal is that the LPFC is organized hierarchically whereby progressively rostral areas of the LPFC process/represent increasingly abstract information facilitating efficient and flexible cognition. However, support for this theory has been limited. Here, human fMRI data revealed rostral/caudal gradients of abstraction in the LPFC. Dynamic causal modeling revealed asymmetrical LPFC interactions indicative of hierarchical processing. Contrary to dominant assumptions, the relative strength of efferent versus afferent connections positioned mid LPFC as the apex of the hierarchy. Furthermore, cognitive demands induced connectivity modulations towards mid LPFC consistent with a role in integrating information for control operations. Moreover, the strengths of these dynamics were related to trait-measured higher-level cognitive ability. Collectively, these results suggest that the LPFC is hierarchically organized with the mid LPFC positioned to synthesize abstract and concrete information to control behavior. PMID:26999822

  11. Nature experience reduces rumination and subgenual prefrontal cortex activation.

    PubMed

    Bratman, Gregory N; Hamilton, J Paul; Hahn, Kevin S; Daily, Gretchen C; Gross, James J

    2015-07-14

    Urbanization has many benefits, but it also is associated with increased levels of mental illness, including depression. It has been suggested that decreased nature experience may help to explain the link between urbanization and mental illness. This suggestion is supported by a growing body of correlational and experimental evidence, which raises a further question: what mechanism(s) link decreased nature experience to the development of mental illness? One such mechanism might be the impact of nature exposure on rumination, a maladaptive pattern of self-referential thought that is associated with heightened risk for depression and other mental illnesses. We show in healthy participants that a brief nature experience, a 90-min walk in a natural setting, decreases both self-reported rumination and neural activity in the subgenual prefrontal cortex (sgPFC), whereas a 90-min walk in an urban setting has no such effects on self-reported rumination or neural activity. In other studies, the sgPFC has been associated with a self-focused behavioral withdrawal linked to rumination in both depressed and healthy individuals. This study reveals a pathway by which nature experience may improve mental well-being and suggests that accessible natural areas within urban contexts may be a critical resource for mental health in our rapidly urbanizing world. PMID:26124129

  12. Lateral Prefrontal Cortex Contributes to Fluid Intelligence Through Multinetwork Connectivity.

    PubMed

    Cole, Michael W; Ito, Takuya; Braver, Todd S

    2015-10-01

    Our ability to effectively adapt to novel circumstances--as measured by general fluid intelligence--has recently been tied to the global connectivity of lateral prefrontal cortex (LPFC). Global connectivity is a broad measure that summarizes both within-network connectivity and across-network connectivity. We used additional graph theoretical measures to better characterize the nature of LPFC connectivity and its relationship with fluid intelligence. We specifically hypothesized that LPFC is a connector hub with an across-network connectivity that contributes to fluid intelligence independent of within-network connectivity. We verified that LPFC was in the top 10% of brain regions in terms of across-network connectivity, suggesting it is a strong connector hub. Importantly, we found that the LPFC across-network connectivity predicted individuals' fluid intelligence and this correlation remained statistically significant when controlling for global connectivity (which includes within-network connectivity). This supports the conclusion that across-network connectivity independently contributes to the relationship between LPFC connectivity and intelligence. These results suggest that LPFC contributes to fluid intelligence by being a connector hub with a truly global multisystem connectivity throughout the brain. PMID:26165732

  13. Flexible neural mechanisms of cognitive control within human prefrontal cortex.

    PubMed

    Braver, Todd S; Paxton, Jessica L; Locke, Hannah S; Barch, Deanna M

    2009-05-01

    A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) were examined that, in a prior study, exhibited contrasting temporal dynamics between older and younger adults during performance of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit a proactive control pattern (primarily cue-based activation), whereas in older adults a reactive control pattern was found (primarily probe-based activation). In the current study, we found that following a period of task-strategy training, these older adults exhibited a proactive shift within a subset of the PFC regions, normalizing their activity dynamics toward young adult patterns. Conversely, under conditions of penalty-based monetary incentives, the younger adults exhibited a reactive shift some of the same regions, altering their temporal dynamics toward the older adult baseline pattern. These experimentally induced crossover patterns of temporal dynamics provide strong support for dual modes of cognitive control that can be flexibly shifted within PFC regions, via modulation of neural responses to changing task conditions or behavioral goals. PMID:19380750

  14. Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia.

    PubMed

    Deppermann, S; Notzon, S; Kroczek, A; Rosenbaum, D; Haeussinger, F B; Diemer, J; Domschke, K; Fallgatter, A J; Ehlis, A-C; Zwanzger, P

    2016-07-01

    A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further. PMID:26996315

  15. Capturing the temporal evolution of choice across prefrontal cortex.

    PubMed

    Hunt, Laurence T; Behrens, Timothy E J; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

    2015-01-01

    Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. PMID:26653139

  16. Morphometric Correlation of Impulsivity in Medial Prefrontal Cortex

    PubMed Central

    Cho, Sang Soo; Pellecchia, Giovanna; Aminian, Kelly; Ray, Nicola; Segura, Barbara; Obeso, Ignacio

    2014-01-01

    Impulsivity is a complex behaviour composed of different domains encompassing behavioural disinhibition, risky decision-making and delay discounting abnormalities. To investigate regional brain correlates between levels of individual impulsivity and grey matter volume, we performed voxel-based morphometric correlation analysis in 34 young, healthy subjects using impulsivity scores measured with Barratt Impulsivity Scale-11 and computerized Kirby’s delay discounting task. The VBM analysis showed that impulsivity appears to be reliant on a network of cortical (medial prefrontal cortex and dorsolateral prefrontal cortex) and subcortical (ventral striatum) structures emphasizing the importance of brain networks associated with reward related decision-making in daily life as morphological biomarkers for impulsivity in a normal healthy population. While our results in healthy volunteers may not directly extend to pathological conditions, they provide an insight into the mechanisms of impulsive behaviour in patients with abnormalities in prefrontal/frontal-striatal connections, such as in drug abuse, pathological gambling, ADHD and Parkinson’s disease. PMID:23274773

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

    PubMed

    Ferrari, Chiara; Lega, Carlotta; Tamietto, Marco; Nadal, Marcos; Cattaneo, Zaira

    2015-06-01

    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 involved in high-level processes, so how does its activity relate to beauty appreciation? To shed light on this, we asked male and female participants to evaluate the attractiveness of faces of the same and other sex prior and after transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC). We found that increasing excitability via anodal tDCS in the right but not in the left DLPFC increased perceived attractiveness of the faces, irrespective of the sex of the faces or the sex of the viewers. Identical stimulation over the same site did not affect estimation of other facial characteristics, such as age, thereby suggesting that the effects of anodal tDCS over the right DLPFC might be selective for facial attractiveness, and might not generalize to decisions concerning other facial attributes. Overall, our data suggest that the right DLPFC plays a causal role in explicit judgment of facial attractiveness. The mechanisms mediating such effect are discussed. PMID:25912761

  18. Prefrontal cortex contributions to episodic retrieval monitoring and evaluation.

    PubMed

    Cruse, Damian; Wilding, Edward L

    2009-11-01

    Although the prefrontal cortex (PFC) plays roles in episodic memory judgments, the specific processes it supports are not understood fully. Event-related potential (ERP) studies of episodic retrieval have revealed an electrophysiological modulation - the right-frontal ERP old/new effect - which is thought to reflect activity in PFC. The functional significance of this old/new effect remains a matter of debate, and this study was designed to test two accounts: (i) that the effect indexes processes linked to the monitoring or evaluation of the products of retrieval in service of task demands, or (ii) that it indexes the number of internal decisions required for a task judgment. Participants studied words in one of two colours. In a subsequent retrieval task, old (studied) and new words were presented in a neutral colour. Participants made initial old/new judgments, along with study colour judgments to words thought to be old. They also indicated their confidence (high/low) in the colour decision. Right-frontal ERP old/new effects were larger for high than for low confidence correct colour judgments, and the magnitude of the right-frontal effect was correlated with the proportions of low confidence judgments that were made. Because the numbers of decisions associated with these response categories are equivalent, these findings do not support a decision-based account of the right-frontal ERP old/new effect. Rather, the correlation between confidence and the magnitude of the effect links it with retrieval monitoring and evaluation processes. PMID:19523968

  19. Disconnection Between Amygdala and Medial Prefrontal Cortex in Psychotic Disorders.

    PubMed

    Mukherjee, Prerona; Sabharwal, Amri; Kotov, Roman; Szekely, Akos; Parsey, Ramin; Barch, Deanna M; Mohanty, Aprajita

    2016-07-01

    Distracting emotional information impairs attention more in schizophrenia (SCZ) than in never-psychotic individuals. However, it is unclear whether this impairment and its neural circuitry is indicative generally of psychosis, or specifically of SCZ, and whether it is even more specific to certain SCZ symptoms (eg, deficit syndrome). It is also unclear if this abnormality contributes to impaired behavioral performance and real-world functioning. Functional imaging data were recorded while individuals with SCZ, bipolar disorder with psychosis (BDP) and no history of psychotic disorders (CON) attended to identity of faces while ignoring their emotional expressions. We examined group differences in functional connectivity between amygdala, involved in emotional evaluation, and sub-regions of medial prefrontal cortex (MPFC), involved in emotion regulation and cognitive control. Additionally, we examined correlation of this connectivity with deficit syndrome and real-world functioning. Behaviorally, SCZ showed the worst accuracy when matching the identity of emotional vs neutral faces. Neurally, SCZ showed lower amygdala-MPFC connectivity than BDP and CON. BPD did not differ from CON, neurally or behaviorally. In patients, reduced amygdala-MPFC connectivity during emotional distractors was related to worse emotional vs neutral accuracy, greater deficit syndrome severity, and unemployment. Thus, reduced amygdala-MPFC functional connectivity during emotional distractors reflects a deficit that is specific to SCZ. This reduction in connectivity is associated with worse clinical and real-world functioning. Overall, these findings provide support for the specificity and clinical utility of amygdala-MPFC functional connectivity as a potential neural marker of SCZ. PMID:26908926

  20. Medial Prefrontal Cortex: Adding Value to Imagined Scenarios

    PubMed Central

    Lin, Wen-Jing; Horner, Aidan J.; Bisby, James A.; Burgess, Neil

    2016-01-01

    The medial prefrontal cortex (mPFC) is consistently implicated in the network supporting autobiographical memory. Whereas more posterior regions in this network have been related to specific processes, such as the generation of visuospatial imagery or the association of items and contexts, the functional contribution of the mPFC remains unclear. However, the involvement of mPFC in estimation of value during decision-making suggests that it might play a similar role in memory. We investigated whether mPFC activity reflects the subjective value of elements in imagined scenarios. Participants in an MRI scanner imagined scenarios comprising a spatial context, a physiological state of need (e.g., thirst), and two items that could be congruent (e.g., drink) or incongruent (e.g., food) with the state of need. Memory for the scenarios was tested outside the scanner. Our manipulation of subjective value by imagined need was verified by increased subjective ratings of value for congruent items and improved subsequent memory for them. Consistent with our hypothesis, fMRI signal in mPFC reflected the modulation of an item’s subjective value by the imagined physiological state, suggesting the mPFC selectively tracked subjective value within our imagination paradigm. Further analyses showed uncorrected effects in non-mPFC regions, including increased activity in the insula when imagining states of need, the caudate nucleus when imagining congruent items, and the anterior hippocampus/amygdala when imagining subsequently remembered items. We therefore provide evidence that the mPFC plays a role in constructing the subjective value of the components of imagined scenarios and thus potentially in reconstructing the value of components of autobiographical recollection. PMID:26042501

  1. Complementary Patterns of Direct Amygdala and Hippocampal Projections to the Macaque Prefrontal Cortex

    PubMed Central

    Aggleton, John P.; Wright, Nicholas F.; Rosene, Douglas L.; Saunders, Richard C.

    2015-01-01

    The projections from the amygdala and hippocampus (including subiculum and presubiculum) to prefrontal cortex were compared using anterograde tracers injected into macaque monkeys (Macaca fascicularis, Macaca mulatta). Almost all prefrontal areas were found to receive some amygdala inputs. These connections, which predominantly arose from the intermediate and magnocellular basal nucleus, were particularly dense in parts of the medial and orbital prefrontal cortex. Contralateral inputs were not, however, observed. The hippocampal projections to prefrontal areas were far more restricted, being confined to the ipsilateral medial and orbital prefrontal cortex (within areas 11, 13, 14, 24a, 32, and 25). These hippocampal projections principally arose from the subiculum, with the fornix providing the sole route. Thus, while the lateral prefrontal cortex essentially receives only amygdala inputs, the orbital prefrontal cortex receives both amygdala and hippocampal inputs, though these typically target different areas. Only in medial prefrontal cortex do direct inputs from both structures terminate in common sites. But, even when convergence occurs within an area, the projections predominantly terminate in different lamina (hippocampal inputs to layer III and amygdala inputs to layers I, II, and VI). The resulting segregation of prefrontal inputs could enable the parallel processing of different information types in prefrontal cortex. PMID:25715284

  2. Synaptic Cytoskeletal Plasticity in the Prefrontal Cortex Following Psychostimulant Exposure.

    PubMed

    DePoy, Lauren M; Gourley, Shannon L

    2015-09-01

    Addiction is characterized by maladaptive decision-making, a loss of control over drug consumption and habit-like drug seeking despite adverse consequences. These cognitive changes may reflect the effects of drugs of abuse on prefrontal cortical neurobiology. Here, we review evidence that amphetamine and cocaine fundamentally remodel the structure of excitatory neurons in the prefrontal cortex. We summarize evidence in particular that these psychostimulants have opposing effects in the medial and orbital prefrontal cortices ('mPFC' and 'oPFC', respectively). For example, amphetamine and cocaine increase dendrite length and spine density in the mPFC, while dendrites are impoverished and dendritic spines are eliminated in the oPFC. We will discuss evidence that certain cytoskeletal regulatory proteins expressed in the oPFC and implicated in postnatal (adolescent) neural development also regulate behavioral sensitivity to cocaine. These findings potentially open a window of opportunity for the identification of novel pharmacotherapeutic targets in the treatment of drug abuse disorders in adults, as well as in drug-vulnerable adolescent populations. Finally, we will discuss the behavioral implications of drug-related dendritic spine elimination in the oPFC, with regard to reversal learning tasks and tasks that assess the development of reward-seeking habits, both used to model aspects of addiction in rodents. PMID:25951902

  3. Higher Order Spike Synchrony in Prefrontal Cortex during Visual Memory

    PubMed Central

    Pipa, Gordon; Munk, Matthias H. J.

    2009-01-01

    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 seven sites exhibit performance dependent modulation of their spike synchronization. PMID:21713065

  4. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression.

    PubMed

    Andersen, Anders H; Smith, Charles D; Slevin, John T; Kryscio, Richard J; Martin, Catherine A; Schmitt, Frederick A; Blonder, Lee X

    2015-01-01

    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. PMID:26793404

  5. Analysis of oxysterols and cholesterol in prefrontal cortex of suicides.

    PubMed

    Freemantle, Erika; Chen, Gary Gang; Cruceanu, Cristiana; Mechawar, Naguib; Turecki, Gustavo

    2013-07-01

    Brain oxysterol levels, which are enzymatic oxidation products of cholesterol (Chl), have been proposed to reflect the dynamic process of physiological synapse maintenance and repair of nerve terminals within the central nervous system (CNS), due to the turnover of membrane Chl. Modifications of oxysterols have important implications in neurological conditions, especially in neurodegenerative and psychiatric disorders in which alterations of synaptic plasticity or cell signalling are implicated, such as depression. Oxysterols can diffuse across the blood-brain barrier and have been hypothesized to provide a mechanism by which the brain can eliminate excess Chl to maintain a steady state. Relations of 24-hydroxycholesterol (24OH) and 27-hydroxycholesterol (27OH) specifically may provide a depiction of CNS Chl homeostasis. Thus, the objective of this study was to integrate oxysterol measures and gene expression measures in an effort to identify how they may relate to depression and suicide. Using post-mortem human prefrontal cortex tissue, quantification of metabolites by GC-MS and gene expression by qRT-PCR were performed with the aim to provide a characterization of enzymatic oxidative Chl homeostasis. Results show a significant increase in 24OH, which suggests a higher turnover of Chl to 24OH in the prefrontal cortex of suicide cases. An increase in 24OH may, in combination with liver-X receptor activation, explain the observed reduction of low central and peripheral Chl in suicide and would have implications for synapse maintenance and loss in the neuropathology of depression and suicide. PMID:23369504

  6. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression

    PubMed Central

    Andersen, Anders H.; Smith, Charles D.; Slevin, John T.; Kryscio, Richard J.; Martin, Catherine A.; Schmitt, Frederick A.; Blonder, Lee X.

    2015-01-01

    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. PMID:26793404

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

    ERIC Educational Resources Information Center

    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…

  8. Dyspnea-Related Cues Engage the Prefrontal Cortex

    PubMed Central

    Herigstad, Mari; Hayen, Anja; Evans, Eleanor; Hardinge, Frances M.; Davies, Robert J.; Wiech, Katja

    2015-01-01

    BACKGROUND: Dyspnea is the major source of disability in COPD. In COPD, environmental cues (eg, the prospect of having to climb stairs) become associated with dyspnea and may trigger dyspnea even before physical activity commences. We hypothesized that brain activation relating to such cues would be different between patients with COPD and healthy control subjects, reflecting greater engagement of emotional mechanisms in patients. METHODS: Using functional MRI (FMRI), we investigated brain responses to dyspnea-related word cues in 41 patients with COPD and 40 healthy age-matched control subjects. We combined these findings with scores on self-report questionnaires, thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enabled identification of brain networks responsible for pain processing despite absence of a physical challenge. RESULTS: Patients with COPD demonstrated activation in the medial prefrontal cortex and anterior cingulate cortex, which correlated with the visual analog scale (VAS) response to word cues. This activity independently correlated with patient responses on questionnaires of depression, fatigue, and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex, and precuneus correlated with the VAS dyspnea scale but not with the questionnaires. CONCLUSIONS: The findings suggest that engagement of the emotional circuitry of the brain is important for interpretation of dyspnea-related cues in COPD and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and the findings suggest that such mechanisms may be relevant in COPD. PMID:26134891

  9. Going and stopping: dichotomies in behavioral control by the prefrontal cortex.

    PubMed

    Gourley, Shannon L; Taylor, Jane R

    2016-04-26

    The rodent dorsal medial prefrontal cortex (PFC), specifically the prelimbic cortex (PL), regulates the expression of conditioned fear and behaviors interpreted as reward seeking. Meanwhile, the ventral medial PFC, namely the infralimbic cortex (IL), is essential to extinction conditioning in both appetitive and aversive domains. Here we review evidence that supports, or refutes, this "PL-go/IL-stop" dichotomy. We focus on the extinction of conditioned fear and the extinction and reinstatement of cocaine- or heroin-reinforced responding following abstinence. We then synthesize evidence that the PL is essential for developing goal-directed response strategies, while the IL supports habit behavior. Finally, we propose that some functions of the orbital PFC parallel those of the medial PFC in the regulation of response selection. Integration of these discoveries may provide points of intervention for inhibiting untethered drug seeking in drug use disorders, extinction failures in post-traumatic stress disorder, or co-morbidities between the two. PMID:27116390

  10. Memory for frequency in rats: role of the hippocampus and medial prefrontal cortex.

    PubMed

    Kesner, R P

    1990-05-01

    On a radial arm maze rats were tested for frequency memory of specific spatial locations, a task that presumably involves the coding of temporal information. On any trial during the study phase rats were allowed to visit three different spatial locations only once and one spatial location twice. During the test phase the rats were given a choice between a spatial location that had been visited once and spatial location that had been visited twice. The rats were reinforced for selecting the twice-visited spatial location. The number of spatial locations between a repetition (lag) was varied from one to three. After extensive training rats displayed memory for frequency only for a lag of three spatial locations, i.e., they displayed a repetition lag effect. Animals then received control, medial prefrontal cortex, or hippocampal lesions. Upon subsequent retests control rats continued to display frequency memory, but animals with medial prefrontal cortex or hippocampal lesions displayed a marked impairment. These data support the idea that both the hippocampus and medial prefrontal cortex code temporal order information. PMID:2350324

  11. Capturing the temporal evolution of choice across prefrontal cortex

    PubMed Central

    Hunt, Laurence T; Behrens, Timothy EJ; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

    2015-01-01

    Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi.org/10.7554/eLife.11945.001 PMID:26653139

  12. The relationship between brain cortical activity and brain oxygenation in the prefrontal cortex during hypergravity exposure.

    PubMed

    Smith, Craig; Goswami, Nandu; Robinson, Ryan; von der Wiesche, Melanie; Schneider, Stefan

    2013-04-01

    Artificial gravity has been proposed as a method to counteract the physiological deconditioning of long-duration spaceflight; however, the effects of hypergravity on the central nervous system has had little study. The study aims to investigate whether there is a relationship between prefrontal cortex brain activity and prefrontal cortex oxygenation during exposure to hypergravity. Twelve healthy participants were selected to undergo hypergravity exposure aboard a short-arm human centrifuge. Participants were exposed to hypergravity in the +Gz axis, starting from 0.6 +Gz for women, and 0.8 +Gz for men, and gradually increasing by 0.1 +Gz until the participant showed signs of syncope. Brain cortical activity was measured using electroencephalography (EEG) and localized to the prefrontal cortex using standard low-resolution brain electromagnetic tomography (LORETA). Prefrontal cortex oxygenation was measured using near-infrared spectroscopy (NIRS). A significant increase in prefrontal cortex activity (P < 0.05) was observed during hypergravity exposure compared with baseline. Prefrontal cortex oxygenation was significantly decreased during hypergravity exposure, with a decrease in oxyhemoglobin levels (P < 0.05) compared with baseline and an increase in deoxyhemoglobin levels (P < 0.05) with increasing +Gz level. No significant correlation was found between prefrontal cortex activity and oxy-/deoxyhemoglobin. It is concluded that the increase in prefrontal cortex activity observed during hypergravity was most likely not the result of increased +Gz values resulting in a decreased oxygenation produced through hypergravity exposure. No significant relationship between prefrontal cortex activity and oxygenation measured by NIRS concludes that brain activity during exposure to hypergravity may be difficult to measure using NIRS. Instead, the increase in prefrontal cortex activity might be attributable to psychological stress, which could pose a problem for the use of a

  13. The rostral prefrontal cortex underlies individual differences in working memory capacity: An approach from the hierarchical model of the cognitive control.

    PubMed

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

    2015-10-01

    Neuroimaging and behavioral evidence has suggested that the lateral prefrontal cortex is involved in individual differences in working memory capacity (WMC). However, few studies have localized the neural structures that differentiate high and low WMC individuals, considering the functional architecture of the prefrontal cortex. The present study aimed to identify a frontal region that underlies individual differences from the perspective of the hierarchical architecture of the frontal cortex. By manipulating an episodic factor of cognitive control (control in selecting an appropriate task set according to a temporal context) and using a parametric modulation analysis, we found that both high- and low- WMC individuals have similar activation patterns in the premotor cortex (BA6, 8), caudal prefrontal cortex (BA44, 45), and frontopolar cortex (BA10, 11), but differed in the rostral part of the prefrontal cortex (BA46/47); high WMC individuals showed greater activation in the higher episodic control condition, whereas low WMC individuals showed reduced activation when episodic control was required. Similar patterns of activation were found in the right inferior parietal and middle/inferior temporal cortices. These results indicate that the rostral prefrontal cortex, which supports episodic cognitive control, possibly by sending a weighting signal toward the inferior parietal and middle/inferior temporal cortices that modulate saliency and sensory processing, underlies individual differences in WMC. Episodic control account, which considers the organization of the prefrontal cortex, fits well with previous findings of individual differences in WMC. PMID:26280275

  14. The Cortical Connectivity of the Prefrontal Cortex in the Monkey Brain

    PubMed Central

    Yeterian, Edward H.; Pandya, Deepak N.; Tomaiuolo, Francesco; Petrides, Michael

    2011-01-01

    One dimension of understanding the functions of the prefrontal cortex is knowledge of cortical connectivity. We have surveyed three aspects of prefrontal cortical connections: local projections (within the frontal lobe), the termination patterns of long association (post-Rolandic) projections, and the trajectories of major fiber pathways. The local connections appear to be organized in relation to dorsal (hippocampal origin) and ventral (paleocortical origin) architectonic trends. According to the proposal of a dual origin of the cerebral cortex, cortical areas can be traced as originating from archicortex (hippocampus) on the one hand, and paleocortex, on the other hand, in a stepwise manner (e.g., Sanides, 1969; Pandya and Yeterian, 1985). Prefrontal areas within each trend are connected with less architectonically differentiated areas, and, on the other hand, with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend. The long connections of the prefrontal cortex with post-Rolandic regions seem to be organized preferentially in relation to dorsal and ventral prefrontal architectonic trends. Prefrontal areas are connected with post-Rolandic auditory, visual and somatosensory association areas, and with multimodal and paralimbic regions. This long connectivity likely works in conjunction with local connections to serve prefrontal cortical functions. The afferent and efferent connections of the prefrontal cortex with post-Rolandic regions are conveyed by specific long association pathways. These pathways as well appear to be organized in relation to dorsal and ventral prefrontal architectonic trends. Finally, although prefrontal areas have preferential connections in relation to dual architectonic trends, it is clear that there are interconnections between and among areas in each trend, which may provide a substrate for the overall integrative function of the prefrontal cortex. Prefrontal

  15. Response of dorsomedial prefrontal cortex predicts altruistic behavior

    PubMed Central

    Waytz, Adam; Zaki, Jamil; Mitchell, Jason P.

    2012-01-01

    Human beings have an unusual proclivity for altruistic behavior, and recent commentators have suggested that these prosocial tendencies arise from our unique capacity to understand the minds of others (i.e., to mentalize). The current studies test this hypothesis by examining the relation between altruistic behavior and the reflexive engagement of a neural system reliably associated with mentalizing. Results indicated that activity in the dorsomedial prefrontal cortex (dorsal MPFC)—a region consistently involved in understanding others’ mental states—predicts both monetary donations to others and time spent helping others. These findings address long-standing questions about the proximate source of human altruism by suggesting that prosocial behavior results, in part, from our broader tendency for social-cognitive thought. PMID:22649243

  16. Prefrontal cortex mediation of cognitive enhancement in rewarding motivational contexts.

    PubMed

    Jimura, Koji; Locke, Hannah S; Braver, Todd S

    2010-05-11

    Increasing the reward value of behavioral goals can facilitate cognitive processes required for goal achievement. This facilitation may be accomplished by the dynamic and flexible engagement of cognitive control mechanisms operating in distributed brain regions. It is still not clear, however, what are the characteristics of individuals, situations, and neural activation dynamics that optimize motivation-linked cognitive enhancement. Here we show that highly reward-sensitive individuals exhibited greater improvement of working memory performance in rewarding contexts, but exclusively on trials that were not rewarded. This effect was mediated by a shift in the temporal dynamics of activation within right lateral prefrontal cortex, from a transient to predominantly tonic mode, with an additional anticipatory transient boost. In contexts with intermittent rewards, a strategy of proactive cognitive control may enable globally optimal performance to facilitate reward attainment. Reward-sensitive individuals appear preferentially motivated to adopt this resource-demanding strategy, resulting in paradoxical benefits selectively for nonrewarded events. PMID:20421489

  17. Increased prefrontal cortex neurogranin enhances plasticity and extinction learning.

    PubMed

    Zhong, Ling; Brown, Joshua; Kramer, Audra; Kaleka, Kanwardeep; Petersen, Amber; Krueger, Jamie N; Florence, Matthew; Muelbl, Matthew J; Battle, Michelle; Murphy, Geoffrey G; Olsen, Christopher M; Gerges, Nashaat Z

    2015-05-13

    Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction. PMID:25972176

  18. Damage to ventromedial prefrontal cortex impairs judgment of harmful intent

    PubMed Central

    Young, Liane; Bechara, Antoine; Tranel, Daniel; Damasio, Hanna; Hauser, Marc; Damasio, Antonio

    2011-01-01

    Summary Moral judgments, whether delivered in ordinary experience or in the courtroom, depend on our ability to infer intentions. We forgive unintentional or accidental harms and condemn failed attempts to harm. Prior work demonstrates that patients with damage to the ventromedial prefrontal cortex (VMPC) deliver abnormal judgments in response to moral dilemmas, and that these patients are especially impaired in triggering emotional responses to inferred or abstract events (e.g., intentions), as opposed to real or actual outcomes. We therefore predicted that VMPC patients would deliver abnormal moral judgments of harmful intentions in the absence of harmful outcomes, as in failed attempts to harm. This prediction was confirmed in the current study: VMPC patients judged attempted harms including attempted murder as more morally permissible relative to controls. These results highlight the critical role of the VMPC in processing harmful intent for moral judgment. PMID:20346759

  19. Damage to the ventromedial prefrontal cortex reduces interpersonal disgust

    PubMed Central

    Ciaramelli, Elisa; Sperotto, Rebecca G.; Mattioli, Flavia

    2013-01-01

    Disgust for contaminating objects (core disgust), immoral behaviors (moral disgust) and unsavory others (interpersonal disgust), have been assumed to be closely related. It is not clear, however, whether different forms of disgust are mediated by overlapping or specific neural substrates. We report that 10 patients with damage to the ventromedial prefrontal cortex (vmPFC) avoided behaviors that normally elicit interpersonal disgust (e.g. using the scarf of a busker) less frequently than healthy and brain-damaged controls, whereas they avoided core and moral disgust elicitors at normal rates. These results indicate that different forms of disgust are dissociated neurally. We propose that the vmPFC is causally (and selectively) involved in mediating interpersonal disgust, shaping patterns of social avoidance and approach. PMID:22842816

  20. Increased Prefrontal Cortex Neurogranin Enhances Plasticity and Extinction Learning

    PubMed Central

    Zhong, Ling; Brown, Joshua; Kramer, Audra; Kaleka, Kanwardeep; Petersen, Amber; Krueger, Jamie N.; Florence, Matthew; Muelbl, Matthew J.; Battle, Michelle; Murphy, Geoffrey G.; Olsen, Christopher M.

    2015-01-01

    Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction. PMID:25972176

  1. Behavioral effects of congenital ventromedial prefrontal cortex malformation

    PubMed Central

    2011-01-01

    Background A detailed behavioral profile associated with focal congenital malformation of the ventromedial prefrontal cortex (vmPFC) has not been reported previously. Here we describe a 14 year-old boy, B.W., with neurological and psychiatric sequelae stemming from focal cortical malformation of the left vmPFC. Case Presentation B.W.'s behavior has been characterized through extensive review Patience of clinical and personal records along with behavioral and neuropsychological testing. A central feature of the behavioral profile is severe antisocial behavior. He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance. Conclusions The vmPFC has a profound contribution to the development of human prosocial behavior. B.W. demonstrates how a congenital lesion to this cortical region severely disrupts this process. PMID:22136635

  2. Involvement of prefrontal cortex in scalar implicatures: evidence from magnetoencephalography

    PubMed Central

    Politzer-Ahles, Stephen; Gwilliams, Laura

    2015-01-01

    The present study investigated the neural correlates of the realisation of scalar inferences, i.e., the interpretation of some as meaning some but not all. We used magnetoencephalography, which has high temporal resolution, to measure neural activity while participants heard stories that included the scalar inference trigger some in contexts that either provide strong cues for a scalar inference or provide weaker cues. The middle portion of the lateral prefrontal cortex (Brodmann area 46) showed an increased response to some in contexts with fewer cues to the inference, suggesting that this condition elicited greater effort. While the results are not predicted by traditional all-or-nothing accounts of scalar inferencing that assume the process is always automatic or always effortful, they are consistent with more recent gradient accounts which predict that the speed and effort of scalar inferences is strongly modulated by numerous contextual factors. PMID:26247054

  3. The Behavioral Relevance of Task Information in Human Prefrontal Cortex.

    PubMed

    Cole, Michael W; Ito, Takuya; Braver, Todd S

    2016-06-01

    Human lateral prefrontal cortex (LPFC) is thought to play a critical role in enabling cognitive flexibility, particularly when performing novel tasks. However, it remains to be established whether LPFC representation of task-relevant information in such situations actually contributes to successful performance. We utilized pattern classification analyses of functional MRI activity to identify novelty-sensitive brain regions as participants rapidly switched between performance of 64 complex tasks, 60 of which were novel. In three of these novelty-sensitive regions-located within distinct areas of left anterior LPFC-trial-evoked activity patterns discriminated correct from error trials. Further, these regions also contained information regarding the task-relevant decision rule, but only for successfully performed trials. This suggests that left anterior LPFC may be particularly important for representing task information that contributes to the cognitive flexibility needed to perform successfully in novel task situations. PMID:25870233

  4. Insights into Human Behavior from Lesions to the Prefrontal Cortex

    PubMed Central

    Szczepanski, Sara M.; Knight, Robert T.

    2014-01-01

    SUMMARY The prefrontal cortex (PFC), a cortical region that was once thought to be functionally insignificant, is now known to play an essential role in the organization and control of goal-directed thought and behavior. Neuroimaging, neurophysiological, and modeling techniques have lead to tremendous advances in our understanding of PFC functions over the last few decades. It should be noted, however, that neurological, neuropathological, and neuropsychological studies have contributed some of the most essential, historical, and often prescient, conclusions regarding the functions of this region. Importantly, examination of patients with brain damage allows one to draw conclusions about whether a brain area is necessary for a particular function. Here, we provide a broad overview of PFC functions based upon behavioral and neural changes resulting from damage to PFC in both human patients and non-human primates. PMID:25175878

  5. MDMA (ecstasy) modulates locomotor and prefrontal cortex sensory evoked activity.

    PubMed

    Atkins, Kristal; Burks, Tilithia; Swann, Alan C; Dafny, Nachum

    2009-12-11

    Ingestion of 3, 4-methylenedioxymethamphetamine (MDMA) leads to heightened response to sensory stimulation; thus, MDMA is referred to as "ecstasy" because it produces pleasurable enhancement of such sensation. There have been no electrophysiological studies that report the consequences of MDMA on sensory input. The present study was initiated to study the effects of acute and chronic MDMA on locomotor activity and sensory evoked field potential from freely behaving rats previously implanted with permanent electrodes in the prefrontal cortex (PFC). The main findings of this study are that: (1) acute MDMA augments locomotor behavior and attenuates the incoming sensory input, (2) chronic treatment of MDMA elicits behavioral sensitization, (3) chronic administration of MDMA results in attenuation of the baseline activity of the sensory evoked field potential, and (4) administration of rechallenge MDMA result in enhancement of the PFC sensory evoked field potential. PMID:19769950

  6. Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

    PubMed

    Hurlemann, René; Arndt, Stephan; Schlaepfer, Thomas E; Reul, Juergen; Maier, Wolfgang; Scheele, Dirk

    2015-01-01

    From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress. PMID:25752944

  7. Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex

    PubMed Central

    Hurlemann, René; Arndt, Stephan; Schlaepfer, Thomas E.; Reul, Juergen; Maier, Wolfgang; Scheele, Dirk

    2015-01-01

    From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress. PMID:25752944

  8. NUCLEUS REUNIENS OF THE MIDLINE THALAMUS: LINK BETWEEN THE MEDIAL PREFRONTAL CORTEX AND THE HIPPOCAMPUS

    PubMed Central

    Vertes, Robert P.; Hoover, Walter B.; Szigeti-Buck, Klara; Leranth, Csaba

    2016-01-01

    The medial prefrontal cortex and the hippocampus serve well recognized roles in memory processing. The hippocampus projects densely to, and exerts strong excitatory actions on, the medial prefrontal cortex. Interestingly, the medial prefrontal cortex, in rats and other species, has no direct return projections to the hippocampus, and few projections to parahippocampal structures including the entorhinal cortex. It is well established that the nucleus reuniens of the midline thalamus is the major source of thalamic afferents to the hippocampus. Since the medial prefrontal cortex also distributes to nucleus reuniens, we examined medial prefrontal connections with populations of nucleus reuniens neurons projecting to hippocampus. We used a combined anterograde and retrograde tracing procedure at the light and electron microscopic levels. Specifically, we made Phaseolus vulgaris-leuccoagglutinin (PHA-L) injections into the medial prefrontal cortex and Fluorogold injections into the hippocampus (CA1/subiculum) and examined termination patterns of anterogradely PHA-L labeled fibers on retrogradely FG labeled cells of nucleus reuniens. At the light microscopic level, we showed that fibers from the medial prefrontal cortex form multiple putative synaptic contacts with dendrites of hippocampally projecting neurons throughout the extent of nucleus reuniens. At ultrastructural level, we showed that medial prefrontal cortical fibers form asymmetric contacts predominantly with dendritic shafts of hippocampally projecting reuniens cells. These findings indicate that nucleus reuniens represents a critical link between the medial prefrontal cortex and the hippocampus. We discuss the possibility that nucleus reuniens gates the flow of information between the medial prefrontal cortex and hippocampus dependent upon attentive/arousal states of the organism. PMID:17292803

  9. Decreased chloride channel expression in the dorsolateral prefrontal cortex in schizophrenia.

    PubMed

    Sullivan, Courtney R; Funk, Adam J; Shan, Dan; Haroutunian, Vahram; McCullumsmith, Robert E

    2015-01-01

    Alterations in GABAergic neurotransmission are implicated in several psychiatric illnesses, including schizophrenia. The Na-K-Cl and K-Cl cotransporters regulate intracellular chloride levels. Abnormalities in cotransporter expression levels could shift the chloride electrochemical gradient and impair GABAergic transmission. In this study, we performed Western blot analysis to investigate whether the Na-K-Cl and K-Cl cotransporter protein is abnormally expressed in the dorsal lateral prefrontal cortex and the anterior cingulate cortex in patients with schizophrenia versus a control group. We found decreased K-Cl cotransporter protein expression in the dorsal lateral prefrontal cortex, but not the anterior cingulate cortex, in subjects with schizophrenia, supporting the hypothesis of region level abnormal GABAergic function in the pathophysiology of schizophrenia. Subjects with schizophrenia off antipsychotic medication at the time of death had decreased K-Cl cotransporter protein expression compared to both normal controls and subjects with schizophrenia on antipsychotics. Our results provide evidence for KCC2 protein abnormalities in schizophrenia and suggest that antipsychotic medications might reverse deficits of this protein in the illness. PMID:25826365

  10. Decreased Chloride Channel Expression in the Dorsolateral Prefrontal Cortex in Schizophrenia

    PubMed Central

    Sullivan, Courtney R.; Funk, Adam J.; Shan, Dan; Haroutunian, Vahram; McCullumsmith, Robert E.

    2015-01-01

    Alterations in GABAergic neurotransmission are implicated in several psychiatric illnesses, including schizophrenia. The Na-K-Cl and K-Cl cotransporters regulate intracellular chloride levels. Abnormalities in cotransporter expression levels could shift the chloride electrochemical gradient and impair GABAergic transmission. In this study, we performed Western blot analysis to investigate whether the Na-K-Cl and K-Cl cotransporter protein is abnormally expressed in the dorsal lateral prefrontal cortex and the anterior cingulate cortex in patients with schizophrenia versus a control group. We found decreased K-Cl cotransporter protein expression in the dorsal lateral prefrontal cortex, but not the anterior cingulate cortex, in subjects with schizophrenia, supporting the hypothesis of region level abnormal GABAergic function in the pathophysiology of schizophrenia. Subjects with schizophrenia off antipsychotic medication at the time of death had decreased K-Cl cotransporter protein expression compared to both normal controls and subjects with schizophrenia on antipsychotics. Our results provide evidence for KCC2 protein abnormalities in schizophrenia and suggest that antipsychotic medications might reverse deficits of this protein in the illness. PMID:25826365

  11. Trace and Contextual Fear Conditioning Require Neural Activity and NMDA Receptor-Dependent Transmission in the Medial Prefrontal Cortex

    ERIC Educational Resources Information Center

    Gilmartin, Marieke R.; Helmstetter, Fred J.

    2010-01-01

    The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a…

  12. Electrolytic Lesions of the Medial Prefrontal Cortex Do Not Interfere with Long-Term Memory of Extinction of Conditioned Fear

    ERIC Educational Resources Information Center

    Garcia, Rene; Chang, Chun-hui; Maren, Stephen

    2006-01-01

    Lesion studies indicate that rats without the medial prefrontal cortex (mPFC) have difficulty recalling fear extinction acquired the previous day. Several electrophysiological studies have also supported this observation by demonstrating that extinction-related increases in neuronal activity in the mPFC participate in expression of fear…

  13. Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex

    PubMed Central

    Tsutsui-Kimura, Iku; Yoshida, Takayuki; Izumi, Takeshi; Yoshioka, Mitsuhiro

    2015-01-01

    Background: Deficits in impulse control are often observed in psychiatric disorders in which abnormalities of the prefrontal cortex are observed, including attention-deficit/hyperactivity disorder and bipolar disorder. We recently found that milnacipran, a serotonin/noradrenaline reuptake inhibitor, could suppress impulsive action in normal rats. However, whether milnacipran could suppress elevated impulsive action in rats with lesions of the ventromedial prefrontal cortex, which is functionally comparable with the human prefrontal cortex, remains unknown. Methods: Selective lesions of the ventromedial prefrontal cortex were made using quinolinic acid in rats previously trained on a 3-choice serial reaction time task. Sham rats received phosphate buffered saline. Following a period of recovery, milnacipran (0 or 10mg/kg/d × 14 days) was orally administered 60 minutes prior to testing on the 3-choice task. After 7 days of drug cessation, Western blotting, immunohistochemistry, electrophysiological analysis, and morphological analysis were conducted. Results: Lesions of the ventromedial prefrontal cortex induced impulsive deficits, and repeated milnacipran ameliorated the impulsive deficit both during the dosing period and after the cessation of the drug. Repeated milnacipran remediated the protein levels of mature brain-derived neurotrophic factor and postsynaptic density-95, dendritic spine density, and excitatory currents in the few surviving neurons in the ventromedial prefrontal cortex of ventromedial prefrontal cortex-lesioned rats. Conclusions: The findings of this study suggest that milnacipran treatment could be a novel strategy for the treatment of psychiatric disorders that are associated with a lack of impulse control. PMID:25522418

  14. Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control.

    PubMed

    Rodrigo, Achala H; Di Domenico, Stefano I; Graves, Bryanna; Lam, Jaeger; Ayaz, Hasan; Bagby, R Michael; Ruocco, Anthony C

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control. PMID:26163672

  15. Ventromedial prefrontal cortex and the regulation of physiological arousal.

    PubMed

    Zhang, Sheng; Hu, Sien; Chao, Herta H; Ide, Jaime S; Luo, Xi; Farr, Olivia M; Li, Chiang-shan R

    2014-07-01

    Neuroimaging studies show a correlation between activity of the ventromedial prefrontal cortex (vmPFC) and skin conductance measurements. However, little is known whether this brain region plays a causal role in regulating physiological arousal. To address this question, we employed Granger causality analysis (GCA) to establish causality between cerebral blood oxygenation level-dependent and skin conductance signals in 24 healthy adults performing a cognitive task during functional magnetic resonance imaging. The results showed that activity of the vmPFC not only negatively correlated with skin conductance level (SCL) but also Granger caused SCL, thus establishing the direction of influence. Importantly, across participants, the strength of Granger causality was negatively correlated to phasic skin conductance responses elicited by external events during the behavioral task. In contrast, activity of the dorsal anterior cingulate cortex positively correlated with SCL but did not show a causal relationship in GCA. These new findings indicate that the vmPFC plays a causal role in regulating physiological arousal. Increased vmPFC activity leads to a decrease in skin conductance. The findings may also advance our understanding of dysfunctions of the vmPFC in mood and anxiety disorders that involve altered control of physiological arousal. PMID:23620600

  16. Dynamic Construction of Stimulus Values in the Ventromedial Prefrontal Cortex

    PubMed Central

    Harris, Alison; Adolphs, Ralph; Camerer, Colin; Rangel, Antonio

    2011-01-01

    Signals representing the value assigned to stimuli at the time of choice have been repeatedly observed in ventromedial prefrontal cortex (vmPFC). Yet it remains unknown how these value representations are computed from sensory and memory representations in more posterior brain regions. We used electroencephalography (EEG) while subjects evaluated appetitive and aversive food items to study how event-related responses modulated by stimulus value evolve over time. We found that value-related activity shifted from posterior to anterior, and from parietal to central to frontal sensors, across three major time windows after stimulus onset: 150–250 ms, 400–550 ms, and 700–800 ms. Exploratory localization of the EEG signal revealed a shifting network of activity moving from sensory and memory structures to areas associated with value coding, with stimulus value activity localized to vmPFC only from 400 ms onwards. Consistent with these results, functional connectivity analyses also showed a causal flow of information from temporal cortex to vmPFC. Thus, although value signals are present as early as 150 ms after stimulus onset, the value signals in vmPFC appear relatively late in the choice process, and seem to reflect the integration of incoming information from sensory and memory related regions. PMID:21695081

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

    PubMed

    Kwapis, Janine L; Jarome, Timothy J; Helmstetter, Fred J

    2014-01-01

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

  18. Successful Face Recognition is Associated with Increased Prefrontal Cortex Activation in Autism Spectrum Disorder

    PubMed Central

    Herrington, John D.; Riley, Meghan E.; Grupe, Daniel W.; Schultz, Robert T.

    2014-01-01

    This study examines whether deficits in visual information processing in ASD can be offset by the recruitment of brain structures involved in selective attention. During functional MRI, 12 children with ASD and 19 control participants completed a selective attention one-back task in which images of faces and houses were superimposed. When attending to faces, the ASD group showed increased activation relative to control participants within multiple prefrontal cortex areas, including dorsolateral prefrontal cortex (DLPFC). DLPFC activation in ASD was associated with increased response times for faces. These data suggest that prefrontal cortex activation may represent a compensatory mechanism for diminished visual information processing abilities. PMID:25234479

  19. Bidirectional prefrontal-hippocampal interactions support context-guided memory.

    PubMed

    Place, Ryan; Farovik, Anja; Brockmann, Marco; Eichenbaum, Howard

    2016-08-01

    We compared the dynamics of hippocampal and prefrontal interactions in rats as they used spatial contexts to guide the retrieval of object memories. Functional connectivity analysis indicated a flow of contextual information from the hippocampus to prefrontal cortex upon the rat's entry into the spatial context. Conversely, upon the onset of object sampling, the direction of information flow reversed, consistent with prefrontal control over the retrieval of context-appropriate hippocampal memory representations. PMID:27322417

  20. Lesions to right prefrontal cortex impair real-world planning through premature commitments.

    PubMed

    Goel, Vinod; Vartanian, Oshin; Bartolo, Angela; Hakim, Lila; Ferraro, Anna Maria; Isella, Valeria; Appollonio, Ildebrando; Drei, Silvia; Nichelli, Paolo

    2013-03-01

    While it is well accepted that the left prefrontal cortex plays a critical role in planning and problem-solving tasks, very little is known about the role of the right prefrontal cortex. We addressed this issue by testing five neurological patients with focal lesions to right prefrontal cortex on a real-world travel planning task, and compared their performance with the performance of five neurological patients with focal lesions to left prefrontal cortex, five neurological patients with posterior lesions, and five normal controls. Only patients with lesions to right prefrontal cortex generated substandard solutions compared to normal controls. Examination of the underlying cognitive processes and strategies revealed that patients with lesions to right prefrontal cortex approached the task at an excessively precise, concrete level compared to normal controls, and very early locked themselves into substandard solutions relative to the comparison group. In contrast, the behavior of normal controls was characterized by a judicious interplay of concrete and abstract levels/modes of representations. We suggest that damage to the right prefrontal system impairs the encoding and processing of more abstract and vague representations that facilitate lateral transformations, resulting in premature commitment to precise concrete patterns, and hasty albeit substandard conclusions (because the space of possibilities has not been properly explored). PMID:23266766

  1. Prefrontal Cortex Activation and Young Driver Behaviour: A fNIRS Study

    PubMed Central

    Foy, Hannah J.; Runham, Patrick; Chapman, Peter

    2016-01-01

    Road traffic accidents consistently show a significant over-representation for young, novice and particularly male drivers. This research examines the prefrontal cortex activation of young drivers and the changes in activation associated with manipulations of mental workload and inhibitory control. It also considers the explanation that a lack of prefrontal cortex maturation is a contributing factor to the higher accident risk in this young driver population. The prefrontal cortex is associated with a number of factors including mental workload and inhibitory control, both of which are also related to road traffic accidents. This experiment used functional near infrared spectroscopy to measure prefrontal cortex activity during five simulated driving tasks: one following task and four overtaking tasks at varying traffic densities which aimed to dissociate workload and inhibitory control. Age, experience and gender were controlled for throughout the experiment. The results showed that younger drivers had reduced prefrontal cortex activity compared to older drivers. When both mental workload and inhibitory control increased prefrontal cortex activity also increased, however when inhibitory control alone increased there were no changes in activity. Along with an increase in activity during overtaking manoeuvres, these results suggest that prefrontal cortex activation is more indicative of workload in the current task. There were no differences in the number of overtakes completed by younger and older drivers but males overtook significantly more than females. We conclude that prefrontal cortex activity is associated with the mental workload required for overtaking. We additionally suggest that the reduced activation in younger drivers may be related to a lack of prefrontal maturation which could contribute to the increased crash risk seen in this population. PMID:27227990

  2. Prefrontal Cortex Glutamate Correlates with Mental Perspective-Taking

    PubMed Central

    Montag, Christiane; Schubert, Florian; Heinz, Andreas; Gallinat, Jürgen

    2008-01-01

    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. PMID:19060949

  3. Prefrontal cortex white matter tracts in prodromal Huntington disease.

    PubMed

    Matsui, Joy T; Vaidya, Jatin G; Wassermann, Demian; Kim, Regina Eunyoung; Magnotta, Vincent A; Johnson, Hans J; Paulsen, Jane S

    2015-10-01

    Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717-3732, 2015. © 2015 Wiley Periodicals, Inc. PMID:26179962

  4. Intentional signal in prefrontal cortex generalizes across different sensory modalities.

    PubMed

    Choi, Kyuwan; Torres, Elizabeth B

    2014-07-01

    Biofeedback-EEG training to learn the mental control of an external device (e.g., a cursor on the screen) has been an important paradigm to attempt to understand the involvements of various areas of the brain in the volitional control and the modulation of intentional thought processes. Often the areas to adapt and to monitor progress are selected a priori. Less explored, however, has been the notion of automatically emerging activation in a particular area or subregions within that area recruited above and beyond the rest of the brain. Likewise, the notion of evoking such a signal as an amodal, abstract one remaining robust across different sensory modalities could afford some exploration. Here we develop a simple binary control task in the context of brain-computer interface (BCI) and use a Bayesian sparse probit classification algorithm to automatically uncover brain regional activity that maximizes task performance. We trained and tested 19 participants using the visual modality for instructions and feedback. Across training blocks we quantified coupling of the frontoparietal nodes and selective involvement of visual and auditory regions as a function of the real-time sensory feedback. The testing phase under both forms of sensory feedback revealed automatic recruitment of the prefrontal cortex with a parcellation of higher strength levels in Brodmann's areas 9, 10, and 11 significantly above those in other brain areas. We propose that the prefrontal signal may be a neural correlate of externally driven intended direction and discuss our results in the context of various aspects involved in the cognitive control of our thoughts. PMID:24259543

  5. Individuals' and groups' intentions in the medial prefrontal cortex.

    PubMed

    Chaminade, Thierry; Kawato, Mitsuo; Frith, Chris

    2011-11-16

    Functional MRI signal was recorded while participants perceived stimuli presented using moving dots. In two conditions of interest, the motion of dots depicted intentions: dots representing the joints of an agent performing an action, and dots representing individual agents behaving contingently. The finding of a common cluster in the posterior part of the medial frontal cortex involved in intentional action representation validates the hypothesis that perception of these two conditions requires a similar internal representation. A cluster responding to the behaving group only is found in the anterior medial frontal cortex. These results support a division of the medial frontal cortex according to social stimuli attributes, with anterior areas responding to higher-order group behaviours integrating the action of multiple individual agents. PMID:21897305

  6. Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS

    PubMed Central

    Hartmann, Christian J.; Lujan, J. Luis; Chaturvedi, Ashutosh; Goodman, Wayne K.; Okun, Michael S.; McIntyre, Cameron C.; Haq, Ihtsham U.

    2016-01-01

    Background: Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS. Methods: We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS. Results: Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non-responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results. Discussion: Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes. PMID:26834544

  7. microRNA Profiles in Parkinson's Disease Prefrontal Cortex

    PubMed Central

    Hoss, Andrew G.; Labadorf, Adam; Beach, Thomas G.; Latourelle, Jeanne C.; Myers, Richard H.

    2016-01-01

    Objective: The goal of this study was to compare the microRNA (miRNA) profile of Parkinson's disease (PD) frontal cortex with normal control brain, allowing for the identification of PD specific signatures as well as study the disease-related phenotypes of onset age and dementia. Methods: Small RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was employed to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses. Results: One twenty five miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q < 0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity = 81.2%, specificity = 88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q = 4.7e-2). Conclusions: Based on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is warranted. PMID:26973511

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

    ERIC Educational Resources Information Center

    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…

  9. Distinct Value Signals in Anterior and Posterior Ventromedial Prefrontal Cortex

    PubMed Central

    Smith, David V.; Hayden, Benjamin Y.; Truong, Trong-Kha; Song, Allen W.; Platt, Michael L.; Huettel, Scott A.

    2010-01-01

    The core feature of an economic exchange is a decision to trade one good for another, based on a comparison of relative value. Economists have long recognized, however, that the value an individual ascribes to a good during decision making (i.e., their relative willingness to trade for that good) does not always map onto the reward they actually experience. Here, we show that experienced value and decision value are represented in distinct regions of ventromedial prefrontal cortex (VMPFC) during the passive consumption of rewards. Participants viewed two categories of rewards – images of faces that varied in their attractiveness and monetary gains and losses – while being scanned using functional magnetic resonance imaging (fMRI). An independent market task, in which participants exchanged some of the money that they earned for brief views of attractive faces, determined the relative decision value associated with each category. We found that activation of anterior VMPFC increased with increasing experienced value, but not decision value, for both reward categories. In contrast, activation of posterior VMPFC predicted each individual's relative decision value for face and monetary stimuli. These results indicate not only that experienced value and decision value are represented in distinct regions of VMPFC, but also that decision value signals are evident even in the absence of an overt choice task. These results endorse the idea that decisions are made by comparing neural representations of the value of different goods encoded in posterior VMPFC in a common, relative currency. PMID:20164333

  10. The role of the medial prefrontal cortex in social categorization.

    PubMed

    Molenberghs, Pascal; Morrison, Samantha

    2014-03-01

    Group membership is an important aspect of our everyday behavior. Recently, we showed that existing relevant in-group labels increased activation in the medial prefrontal cortex (MPFC) compared with out-group labels, suggesting a role of the MPFC in social categorization. However, the question still remains whether this increase in MPFC activation for in-group representation is solely related with previous experience with the in-group. To test this, we randomly assigned participants to a red or blue team and in a subsequent functional magnetic resonance imaging experiment they categorized red and blue team words as belonging to either the in-group or the out-group. Results showed that even under these minimal conditions increased activation was found in the MPFC when participants indicated that they belonged to a group, as compared with when they did not. This effect was found to be associated with the level of group identification. These results confirm the role of MPFC in social categorization. PMID:23175678

  11. Electrical stimulation of the dorsolateral prefrontal cortex improves memory monitoring.

    PubMed

    Chua, Elizabeth F; Ahmed, Rifat

    2016-05-01

    The ability to accurately monitor one's own memory is an important feature of normal memory function. Converging evidence from neuroimaging and lesion studies have implicated the dorsolateral prefrontal cortex (DLPFC) in memory monitoring. Here we used high definition transcranial direct stimulation (HD-tDCS), a non-invasive form of brain stimulation, to test whether the DLPFC has a causal role in memory monitoring, and the nature of that role. We used a metamemory monitoring task, in which participants first attempted to recall the answer to a general knowledge question, then gave a feeling-of-knowing (FOK) judgment, followed by a forced choice recognition task. When participants received DLPFC stimulation, their feeling-of-knowing judgments were better predictors of memory performance, i.e., they had better memory monitoring accuracy, compared to stimulation of a control site, the anterior temporal lobe (ATL). Effects of DLPFC stimulation were specific to monitoring accuracy, as there was no significant increase in memory performance, and if anything, there was poorer memory performance with DLPFC stimulation. Thus we have demonstrated a causal role for the DLPFC in memory monitoring, and showed that electrically stimulating the left DLPFC led people to more accurately monitor and judge their own memory. PMID:26970142

  12. Regulation of prefrontal cortex myelination by the microbiota.

    PubMed

    Hoban, A E; Stilling, R M; Ryan, F J; Shanahan, F; Dinan, T G; Claesson, M J; Clarke, G; Cryan, J F

    2016-01-01

    The prefrontal cortex (PFC) is a key region implicated in a range of neuropsychiatric disorders such as depression, schizophrenia and autism. In parallel, the role of the gut microbiota in contributing to these disorders is emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been instrumental in elucidating the role of the microbiota in many aspects of physiology, especially the role of the microbiota in anxiety-related behaviours, impaired social cognition and stress responsivity. Here we aim to further elucidate the mechanisms of the microbial influence by investigating changes in the homeostatic regulation of neuronal transcription of GF mice within the PFC using a genome-wide transcriptome profiling approach. Our results reveal a marked, concerted upregulation of genes linked to myelination and myelin plasticity. This coincided with upregulation of neural activity-induced pathways, potentially driving myelin plasticity. Subsequent investigation at the ultrastructural level demonstrated the presence of hypermyelinated axons within the PFC of GF mice. Notably, these changes in myelin and activity-related gene expression could be reversed by colonization with a conventional microbiota following weaning. In summary, we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC. PMID:27045844

  13. Context-Dependent Duration Signals in the Primate Prefrontal Cortex.

    PubMed

    Genovesio, Aldo; Seitz, Lucia K; Tsujimoto, Satoshi; Wise, Steven P

    2016-08-01

    The activity of some prefrontal (PF) cortex neurons distinguishes short from long time intervals. Here, we examined whether this property reflected a general timing mechanism or one dependent on behavioral context. In one task, monkeys discriminated the relative duration of 2 stimuli; in the other, they discriminated the relative distance of 2 stimuli from a fixed reference point. Both tasks had a pre-cue period (interval 1) and a delay period (interval 2) with no discriminant stimulus. Interval 1 elapsed before the presentation of the first discriminant stimulus, and interval 2 began after that stimulus. Both intervals had durations of either 400 or 800 ms. Most PF neurons distinguished short from long durations in one task or interval, but not in the others. When neurons did signal something about duration for both intervals, they did so in an uncorrelated or weakly correlated manner. These results demonstrate a high degree of context dependency in PF time processing. The PF, therefore, does not appear to signal durations abstractedly, as would be expected of a general temporal encoder, but instead does so in a highly context-dependent manner, both within and between tasks. PMID:26209845

  14. Action planning in a virtual context after prefrontal cortex damage.

    PubMed

    Zalla, T; Plassiart, C; Pillon, B; Grafman, J; Sirigu, A

    2001-01-01

    Patients with frontal lobe lesions are known to encounter severe problems in the organisation of their behaviour in everyday life. Script generation tasks assess the subject's conceptual ability to formulate and evaluate a coherent and structured plan of action. In the present study, we investigated to what extent neuropsychological deficits observed at the conceptual level of action knowledge lead to impairments in action execution. We examined seven patients with prefrontal cortex damage and sixteen normal subjects. Subjects were first asked to verbally formulate a plan of action and then to use this knowledge for 'executing' the actions in a virtual 3-dimensional interactive apartment presented on a computer screen. The results indicated that the presence of the realistic context improved patients' performance. However, specific impairments were observed in patients in the execution condition, namely actions slips, omissions, failure in initiating actions and purposeless displacements. Moreover, an analysis of planning time showed that, differently of the patients group, normal subjects spent more time during plan execution as compared to plan generation. These results suggest that after a frontal lobe lesion a defective formulation of a routine plan might affect the execution of the corresponding course of actions. PMID:11369400

  15. Medial prefrontal cortex subserves diverse forms of self-reflection.

    PubMed

    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. PMID:20711940

  16. Regulation of prefrontal cortex myelination by the microbiota

    PubMed Central

    Hoban, A E; Stilling, R M; Ryan, F J; Shanahan, F; Dinan, T G; Claesson, M J; Clarke, G; Cryan, J F

    2016-01-01

    The prefrontal cortex (PFC) is a key region implicated in a range of neuropsychiatric disorders such as depression, schizophrenia and autism. In parallel, the role of the gut microbiota in contributing to these disorders is emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been instrumental in elucidating the role of the microbiota in many aspects of physiology, especially the role of the microbiota in anxiety-related behaviours, impaired social cognition and stress responsivity. Here we aim to further elucidate the mechanisms of the microbial influence by investigating changes in the homeostatic regulation of neuronal transcription of GF mice within the PFC using a genome-wide transcriptome profiling approach. Our results reveal a marked, concerted upregulation of genes linked to myelination and myelin plasticity. This coincided with upregulation of neural activity-induced pathways, potentially driving myelin plasticity. Subsequent investigation at the ultrastructural level demonstrated the presence of hypermyelinated axons within the PFC of GF mice. Notably, these changes in myelin and activity-related gene expression could be reversed by colonization with a conventional microbiota following weaning. In summary, we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC. PMID:27045844

  17. Susceptibility to social pressure following ventromedial prefrontal cortex damage.

    PubMed

    Chen, Kuan-Hua; Rusch, Michelle L; Dawson, Jeffrey D; Rizzo, Matthew; Anderson, Steven W

    2015-11-01

    Social pressure influences human behavior including risk taking, but the psychological and neural underpinnings of this process are not well understood. We used the human lesion method to probe the role of ventromedial prefrontal cortex (vmPFC) in resisting adverse social pressure in the presence of risk. Thirty-seven participants (11 with vmPFC damage, 12 with brain damage outside the vmPFC and 14 without brain damage) were tested in driving simulator scenarios requiring left-turn decisions across oncoming traffic with varying time gaps between the oncoming vehicles. Social pressure was applied by a virtual driver who honked aggressively from behind. Participants with vmPFC damage were more likely to select smaller and potentially unsafe gaps under social pressure, while gap selection by the comparison groups did not change under social pressure. Participants with vmPFC damage also showed prolonged elevated skin conductance responses (SCR) under social pressure. Comparison groups showed similar initial elevated SCR, which then declined prior to making left-turn decisions. The findings suggest that the vmPFC plays an important role in resisting explicit and immediately present social pressure with potentially negative consequences. The vmPFC appears to contribute to the regulation of emotional responses and the modulation of decision making to optimize long-term outcomes. PMID:25816815

  18. Thalamic control of layer 1 circuits in prefrontal cortex

    PubMed Central

    Cruikshank, Scott J.; Ahmed, Omar J.; Stevens, Tanya R.; Patrick, Saundra L.; Gonzalez, Amalia N.; Elmaleh, Margot; Connors, Barry W.

    2012-01-01

    Knowledge of thalamocortical (TC) processing comes mainly from studying core thalamic systems that project to middle layers of primary sensory cortices. However, most thalamic relay neurons comprise a matrix of cells that are densest in the “nonspecific” thalamic nuclei and usually target layer 1 of multiple cortical areas. A longstanding hypothesis is that matrix TC systems are crucial for regulating neocortical excitability during changing behavioral states, yet we know almost nothing about the mechanisms of such regulation. It is also unclear whether synaptic and circuit mechanisms that are well established for core sensory TC systems apply to matrix TC systems. Here we describe studies of thalamic matrix influences on mouse prefrontal cortex using optogenetic and in vitro electrophysiology techniques. Channelrhodopsin-2 was expressed in midline and paralaminar (matrix) thalamic neurons, and their layer 1-projecting TC axons were activated optically. Contrary to conventional views, we found that matrix TC projections to layer 1 could transmit relatively strong, fast, high-fidelity synaptic signals. Layer 1 TC projections preferentially drove inhibitory interneurons of layer 1, especially those of the late-spiking subtype, and often triggered feedforward inhibition in both layer 1 interneurons and pyramidal cells of layers 2/3. Responses during repetitive stimulation were far more sustained for matrix than for core sensory TC pathways. Thus, matrix TC circuits appear to be specialized for robust transmission over relatively extended periods, consistent with the sort of persistent activation observed during working memory and potentially applicable to state-dependent regulation of excitability. PMID:23223300

  19. Unilateral deactivation of macaque dorsolateral prefrontal cortex induces biases in stimulus selection.

    PubMed

    Johnston, Kevin; Lomber, Stephen G; Everling, Stefan

    2016-03-01

    Following unilateral brain injury, patients are often unable to detect a stimulus presented in the contralesional field when another is presented simultaneously ipsilesionally. This phenomenon has been referred to as extinction and has been conceptualized as a deficit in selective attention. Although most commonly observed following damage to posterior parietal areas, extinction has been observed following lesions of prefrontal cortex (PFC) in both humans and nonhuman primates. To date, most studies in nonhuman primates have examined lesions of multiple PFC subregions, including the frontal eye fields (FEF). Theoretical accounts of attentional disturbances from human patients, however, also implicate other PFC areas, including the middle frontal gyrus. Here, we investigated the effects of deactivating PFC areas anterior to the FEF on stimulus selection using a free-choice task. Macaque monkeys were presented with two peripheral stimuli appearing either simultaneously, or at varying stimulus onset asynchronies, and their performance was evaluated during unilateral cryogenic deactivation of part of dorsolateral prefrontal cortex or the cortex lining the caudal principal sulcus, the likely homologue of the human middle frontal gyrus. A decreased proportion of saccades was made to stimuli presented in the hemifield contralateral to the deactivated PFC. We also observed increases in reaction times to contralateral stimuli and decreases for stimuli presented in the hemifield ipsilateral to the deactivated hemisphere. In both cases, these results were greatest when both PFC subregions were deactivated. These findings demonstrate that selection biases result from PFC deactivation and support a role of dorsolateral prefrontal subregions anterior to FEF in stimulus selection. PMID:26792881

  20. Altered cerebellar and prefrontal cortex function in rhesus monkeys that previously self-administered cocaine

    PubMed Central

    Porter, Jessica N.; Minhas, Davneet; Lopresti, Brian J.; Price, Julie C.; Bradberry, Charles W.

    2014-01-01

    Rationale Differences in brain function in cocaine users can occur even when frank deficits are not apparent, indicating neuroadaptive consequences of use. Using monkeys to investigate altered metabolic activity following chronic cocaine self-administration allows an assessment of altered function due to cocaine use, without the confound of pre-existing differences or polysubstance use often present in clinical studies. Objectives To evaluate alterations in metabolic function during a working memory task in prefrontal cortex and the cerebellum following one year of chronic cocaine self-administration followed by a 20 month drug-free period. Methods [18F] Fluorodeoxyglucose PET imaging was used to evaluate changes in relative regional metabolic activity associated with a delayed match to sample working memory task. Chronic cocaine animals were compared to a control group, and region of interest analyses focused on the dorsolateral prefrontal cortex (DLPFC) and cerebellum. Results Despite no differences in task performance, in the cocaine group, the cerebellum showed greater metabolic activity during the working memory task (relative to the control task) compared to the control group. There was also a trend towards a significant difference between the groups in DLPFC activity (p=0.054), with the cocaine group exhibiting lower DLPFC metabolic activity during the delay task (relative to the control task) than the control group. Conclusion The results support clinical indications of increased cerebellar activity associated with chronic cocaine exposure. Consistent with evidence of functional interactions between cerebellum and prefrontal cortex, these changes may serve to compensate for potential impairments in functionality of DLPFC. PMID:24733237

  1. Dysregulation of cell death machinery in the prefrontal cortex of human alcoholics

    PubMed Central

    Johansson, Sofia; Ekström, Tomas J.; Marinova, Zoya; Ökvist, Anna; Sheedy, Donna; Garrick, Therese; Harper, Clive; Kuzmin, Alexander; Yakovleva, Tatjana; Bakalkin, Georgy

    2012-01-01

    In human alcoholics, the cell density is decreased in the prefrontal cortex (PFC) and other brain areas. This may be due to persistent activation of cell death pathways. To address this hypothesis, we examined the status of cell death machinery in the dorsolateral PFC in alcoholics. Protein and mRNA expression levels of several key pro- and anti-apoptotic genes were compared in post-mortem samples of 14 male human alcoholics and 14 male controls. The findings do not support the hypothesis. On the contrary, they show that several components of intrinsic apoptotic pathway are decreased in alcoholics. No differences were evident in the motor cortex, which is less damaged in alcoholics and was analysed for comparison. Thus, cell death mechanisms may be dysregulated by inhibition of intrinsic apoptotic pathway in the PFC in human alcoholics. This inhibition may reflect molecular adaptations that counteract alcohol neurotoxicity in cells that survive after many years of alcohol exposure and withdrawal. PMID:18937880

  2. Effects of Physical Exercise on Working Memory and Prefrontal Cortex Function in Post-Stroke Patients.

    PubMed

    Moriya, M; Aoki, C; Sakatani, K

    2016-01-01

    Physical exercise enhances prefrontal cortex activity and improves working memory performance in healthy older adults, but it is not clear whether this remains the case in post-stroke patients. Therefore, the aim of this study was to examine the acute effect of physical exercise on prefrontal cortex activity in post-stroke patients using near-infrared spectroscopy (NIRS). We studied 11 post-stroke patients. The patients performed Sternberg-type working memory tasks before and after moderate intensity aerobic exercise (40 % of maximal oxygen uptake) with a cycling ergometer for 15 min. We measured the NIRS response at the prefrontal cortex during the working memory task. We evaluated behavioral performance (response time and accuracy) of the working memory task. It was found that physical exercise improved behavioral performance of the working memory task compared with the control condition (p < 0.01). In addition, NIRS analysis indicated that physical exercise enhanced prefrontal cortex activation, particularly in the right prefrontal cortex (p < 0.05), during the working memory task compared with the control condition. These findings suggest that the moderate-intensity aerobic exercise enhances prefrontal cortex activity and improves working memory performance in post-stroke patients. PMID:27526144

  3. Development of abstract thinking during childhood and adolescence: the role of rostrolateral prefrontal cortex.

    PubMed

    Dumontheil, Iroise

    2014-10-01

    Rostral prefrontal cortex (RPFC) has increased in size and changed in terms of its cellular organisation during primate evolution. In parallel emerged the ability to detach oneself from the immediate environment to process abstract thoughts and solve problems and to understand other individuals' thoughts and intentions. Rostrolateral prefrontal cortex (RLPFC) is thought to play an important role in supporting the integration of abstract, often self-generated, thoughts. Thoughts can be temporally abstract and relate to long term goals, or past or future events, or relationally abstract and focus on the relationships between representations rather than simple stimulus features. Behavioural studies have provided evidence of a prolonged development of the cognitive functions associated with RLPFC, in particular logical and relational reasoning, but also episodic memory retrieval and prospective memory. Functional and structural neuroimaging studies provide further support for a prolonged development of RLPFC during adolescence, with some evidence of increased specialisation of RLPFC activation for relational integration and aspects of episodic memory retrieval. Topics for future research will be discussed, such as the role of medial RPFC in processing abstract thoughts in the social domain, the possibility of training abstract thinking in the domain of reasoning, and links to education. PMID:25173960

  4. TMS-induced neural noise in sensory cortex interferes with short-term memory storage in prefrontal cortex

    PubMed Central

    Bancroft, Tyler D.; Hogeveen, Jeremy; Hockley, William E.; Servos, Philip

    2014-01-01

    In a previous study, Harris et al. (2002) found disruption of vibrotactile short-term memory after applying single-pulse transcranial magnetic stimulation (TMS) to primary somatosensory cortex (SI) early in the maintenance period, and suggested that this demonstrated a role for SI in vibrotactile memory storage. While such a role is compatible with recent suggestions that sensory cortex is the storage substrate for working memory, it stands in contrast to a relatively large body of evidence from human EEG and single-cell recording in primates that instead points to prefrontal cortex as the storage substrate for vibrotactile memory. In the present study, we use computational methods to demonstrate how Harris et al.'s results can be reproduced by TMS-induced activity in sensory cortex and subsequent feedforward interference with memory traces stored in prefrontal cortex, thereby reconciling discordant findings in the tactile memory literature. PMID:24634653

  5. Cognitive findings after transient global amnesia: role of prefrontal cortex.

    PubMed

    Le Pira, Francesco; Giuffrida, Salvatore; Maci, Tiziana; Reggio, Ester; Zappalà, Giuseppe; Perciavalle, Vincenzo

    2005-01-01

    The aim of this study is to verify, after recovery, the presence of specific patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen patients with the diagnosis of TGA were submitted to a battery of neuropsychological tests and compared to a matched control group. We found significant qualitative and quantitative differences between TGA patients and controls in the California Verbal Learning Test (CLVT) and Rey-Osterrieth Complex Figure Test. Our data support the presence of selective cognitive dysfunctions after the clinical recovery. Moreover, for Verbal Fluency, Digit Span Backward, and Number of Clusters in the CVLT short-term memory test, the relation resulted as positively related with the temporal interval from the TGA episode. Reduction of categorical learning, attention, and qualitative alterations of spatial strategy seem to postulate a planning defect due to a prefrontal impairment. PMID:16422663

  6. Lesions of the orbitofrontal but not medial prefrontal cortex disrupt conditioned reinforcement in primates.

    PubMed

    Pears, Andrew; Parkinson, John A; Hopewell, Lucy; Everitt, Barry J; Roberts, Angela C

    2003-12-01

    The ventromedial prefrontal cortex (PFC) is implicated in affective and motivated behaviors. Damage to this region, which includes the orbitofrontal cortex as well as ventral sectors of medial PFC, causes profound changes in emotional and social behavior, including impairments in certain aspects of decision making. One reinforcement mechanism that may well contribute to these behaviors is conditioned reinforcement, whereby previously neutral stimuli in the environment, by virtue of their association with primary rewards, take on reinforcing value and come to support instrumental action. Conditioned reinforcers are powerful determinants of behavior and can maintain responding over protracted periods of time in the absence of and potentially in conflict with primary reinforcers. It has already been shown that conditioned reinforcement is dependent on the amygdala, and because the amygdala projects to both the orbitofrontal cortex and the medial PFC, the present study determined whether conditioned reinforcement was also dependent on one or the other of these prefrontal regions. Comparison of the behavioral effects of selective excitotoxic lesions of the PFC in the common marmoset revealed that orbitofrontal but not medial PFC lesions disrupted two distinct measures of conditioned reinforcement: (1) acquisition of a new response and (2) sensitivity to conditioned stimulus omission on a second-order schedule. In contrast, the orbitofrontal lesion did not affect sensitivity to primary reinforcement as measured by responding on a progressive-ratio schedule and a home cage consumption test. Together, these findings demonstrate the critical and specific involvement of the orbitofrontal cortex but not the medial PFC in conditioned reinforcement. PMID:14657178

  7. Noradrenergic control of error perseveration in medial prefrontal cortex

    PubMed Central

    Caetano, Marcelo S.; Jin, Lu E.; Harenberg, Linda; Stachenfeld, Kimberly L.; Arnsten, Amy F. T.; Laubach, Mark

    2013-01-01

    The medial prefrontal cortex (mPFC) plays a key role in behavioral variability, action monitoring, and inhibitory control. The functional role of mPFC may change over the lifespan due to a number of aging-related issues, including dendritic regression, increased cAMP signaling, and reductions in the efficacy of neuromodulators to influence mPFC processing. A key neurotransmitter in mPFC is norepinephrine. Previous studies have reported aging-related changes in the sensitivity of mPFC-dependent tasks to noradrenergic agonist drugs, such as guanfacine. Here, we assessed the effects of yohimbine, an alpha-2 noradrenergic antagonist, in cohorts of younger and older rats in a classic test of spatial working memory (using a T-maze). Older rats (23–29 mo.) were impaired by a lower dose of yohimbine compared to younger animals (5–10 mo.). To determine if the drug acts on alpha-2 noradrenergic receptors in mPFC and if its effects are specific to memory-guided performance, we made infusions of yohimbine into mPFC of a cohort of young rats (6 mo.) using an operant delayed response task. The task involved testing rats in blocks of trials with memory- and stimulus-guided performance. Yohimbine selectively impaired memory-guided performance and was associated with error perseveration. Infusions of muscimol (a GABA-A agonist) at the same sites also selectively impaired memory-guided performance, but did not lead to error perseveration. Based on these results, we propose several potential interpretations for the role for the noradrenergic system in the performance of delayed response tasks, including the encoding of previous response locations, task rules (i.e., using a win-stay strategy instead of a win-shift strategy), and performance monitoring (e.g., prospective encoding of outcomes). PMID:23293590

  8. Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

    PubMed Central

    Schiller, Daniela; Kanen, Jonathan W.; LeDoux, Joseph E.; Monfils, Marie-H.; Phelps, Elizabeth A.

    2013-01-01

    Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the nonreminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders. PMID:24277809

  9. Medial prefrontal cortex stimulation modulates the processing of conditioned fear

    PubMed Central

    Guhn, Anne; Dresler, Thomas; Andreatta, Marta; Müller, Laura D.; Hahn, Tim; Tupak, Sara V.; Polak, Thomas; Deckert, Jürgen; Herrmann, Martin J.

    2014-01-01

    The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS−) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS− discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT). PMID:24600362

  10. Noradrenergic control of error perseveration in medial prefrontal cortex.

    PubMed

    Caetano, Marcelo S; Jin, Lu E; Harenberg, Linda; Stachenfeld, Kimberly L; Arnsten, Amy F T; Laubach, Mark

    2012-01-01

    The medial prefrontal cortex (mPFC) plays a key role in behavioral variability, action monitoring, and inhibitory control. The functional role of mPFC may change over the lifespan due to a number of aging-related issues, including dendritic regression, increased cAMP signaling, and reductions in the efficacy of neuromodulators to influence mPFC processing. A key neurotransmitter in mPFC is norepinephrine. Previous studies have reported aging-related changes in the sensitivity of mPFC-dependent tasks to noradrenergic agonist drugs, such as guanfacine. Here, we assessed the effects of yohimbine, an alpha-2 noradrenergic antagonist, in cohorts of younger and older rats in a classic test of spatial working memory (using a T-maze). Older rats (23-29 mo.) were impaired by a lower dose of yohimbine compared to younger animals (5-10 mo.). To determine if the drug acts on alpha-2 noradrenergic receptors in mPFC and if its effects are specific to memory-guided performance, we made infusions of yohimbine into mPFC of a cohort of young rats (6 mo.) using an operant delayed response task. The task involved testing rats in blocks of trials with memory- and stimulus-guided performance. Yohimbine selectively impaired memory-guided performance and was associated with error perseveration. Infusions of muscimol (a GABA-A agonist) at the same sites also selectively impaired memory-guided performance, but did not lead to error perseveration. Based on these results, we propose several potential interpretations for the role for the noradrenergic system in the performance of delayed response tasks, including the encoding of previous response locations, task rules (i.e., using a win-stay strategy instead of a win-shift strategy), and performance monitoring (e.g., prospective encoding of outcomes). PMID:23293590

  11. Molecular influences on working memory circuits in dorsolateral prefrontal cortex.

    PubMed

    Arnsten, Amy F T; Jin, Lu E

    2014-01-01

    The working memory circuits of the primate dorsolateral prefrontal cortex (dlPFC) are modulated in a unique manner, often opposite to the molecular mechanisms needed for long-term memory consolidation. Working memory, our "mental sketch pad" is an ephemeral process, whereby transient, mental representations form the foundation for abstract thought. The microcircuits that generate mental representations are found in deep layer III of the dlPFC, where pyramidal cells excite each other to keep information "in mind" through NMDA receptor synapses on spines. The catecholaminergic and cholinergic arousal systems have rapid and flexible influences on the strength of these connections, thus allowing coordination between arousal and cognitive states. These modulators can rapidly weaken connectivity, for example, as occurs during uncontrollable stress, via feedforward calcium-cAMP signaling opening potassium (K(+)) channels near synapses on spines. Lower levels of calcium-cAMP-K(+) channel signaling provide negative feedback within recurrent excitatory circuits, and help to gate inputs to shape the contents of working memory. There are also explicit mechanisms to inhibit calcium-cAMP signaling and strengthen connectivity, for example, postsynaptic α2A-adrenoceptors on spines. This work has led to the development of the α2A agonist, guanfacine, for the treatment of a variety of dlPFC disorders. In mental illness, there are a variety of genetic insults to the molecules that normally serve to inhibit calcium-cAMP signaling in spines, thus explaining why so many genetic insults can lead to the same phenotype of impaired dlPFC cognitive function. Thus, the molecular mechanisms that provide mental flexibility may also confer vulnerability when dysregulated in cognitive disorders. PMID:24484703

  12. Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats.

    PubMed

    Lima, A; Sardinha, V M; Oliveira, A F; Reis, M; Mota, C; Silva, M A; Marques, F; Cerqueira, J J; Pinto, L; Sousa, N; Oliveira, J F

    2014-07-01

    Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-α-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC. PMID:24419043

  13. Cortical thickness of the dorsolateral prefrontal cortex predicts strategic choices in economic games.

    PubMed

    Yamagishi, Toshio; Takagishi, Haruto; Fermin, Alan de Souza Rodrigues; Kanai, Ryota; Li, Yang; Matsumoto, Yoshie

    2016-05-17

    Human prosociality has been traditionally explained in the social sciences in terms of internalized social norms. Recent neuroscientific studies extended this traditional view of human prosociality by providing evidence that prosocial choices in economic games require cognitive control of the impulsive pursuit of self-interest. However, this view is challenged by an intuitive prosociality view emphasizing the spontaneous and heuristic basis of prosocial choices in economic games. We assessed the brain structure of 411 players of an ultimatum game (UG) and a dictator game (DG) and measured the strategic reasoning ability of 386. According to the reflective norm-enforcement view of prosociality, only those capable of strategically controlling their selfish impulses give a fair share in the UG, but cognitive control capability should not affect behavior in the DG. Conversely, we support the intuitive prosociality view by showing for the first time, to our knowledge, that strategic reasoning and cortical thickness of the dorsolateral prefrontal cortex were not related to giving in the UG but were negatively related to giving in the DG. This implies that the uncontrolled choice in the DG is prosocial rather than selfish, and those who have a thicker dorsolateral prefrontal cortex and are capable of strategic reasoning (goal-directed use of the theory of mind) control this intuitive drive for prosociality as a means to maximize reward when there are no future implications of choices. PMID:27140622

  14. Value signals in the prefrontal cortex predict individual preferences across reward categories.

    PubMed

    Gross, Jörg; Woelbert, Eva; Zimmermann, Jan; Okamoto-Barth, Sanae; Riedl, Arno; Goebel, Rainer

    2014-05-28

    Humans can choose between fundamentally different options, such as watching a movie or going out for dinner. According to the utility concept, put forward by utilitarian philosophers and widely used in economics, this may be accomplished by mapping the value of different options onto a common scale, independent of specific option characteristics (Fehr and Rangel, 2011; Levy and Glimcher, 2012). If this is the case, value-related activity patterns in the brain should allow predictions of individual preferences across fundamentally different reward categories. We analyze fMRI data of the prefrontal cortex while subjects imagine the pleasure they would derive from items belonging to two distinct reward categories: engaging activities (like going out for drinks, daydreaming, or doing sports) and snack foods. Support vector machines trained on brain patterns related to one category reliably predict individual preferences of the other category and vice versa. Further, we predict preferences across participants. These findings demonstrate that prefrontal cortex value signals follow a common scale representation of value that is even comparable across individuals and could, in principle, be used to predict choice. PMID:24872562

  15. Repeated cocaine administration promotes long-term potentiation induction in rat medial prefrontal cortex.

    PubMed

    Huang, Chiung-Chun; Lin, Hsiao-Ju; Hsu, Kuei-Sen

    2007-08-01

    Although drug-induced adaptations in the prefrontal cortex (PFC) may contribute to several core aspects of addictive behaviors, it is not clear yet whether drugs of abuse elicit changes in synaptic plasticity at the PFC excitatory synapses. Here we report that, following repeated cocaine administration (15 mg/kg/day intraperitoneal injection for 5 consecutive days) with a 3-day withdrawal, excitatory synapses to layer V pyramidal neurons in rat medial prefrontal cortex (mPFC) become highly sensitive to the induction of long-term potentiation (LTP) by repeated correlated presynaptic and postsynaptic activity. This promoted LTP induction is caused by cocaine-induced reduction of gamma-aminobutyric acid (GABA)(A) receptor-mediated inhibition of mPFC pyramidal neurons. In contrast, in slices from rats treated with saline or a single dose of cocaine, the same LTP induction protocol did not induce significant LTP unless the blockade of GABA(A) receptors. Blockade of the D1-like receptors specifically prevented the cocaine-induced enhancement of LTP. Repeated cocaine exposure reduced the GABA(A) receptor-mediated synaptic currents in mPFC pyramidal neurons. Biotinylation experiments revealed a significant reduction of surface GABA(A) receptor alpha1 subunit expression in mPFC slices from repeated cocaine-treated rats. These findings support an important role for cocaine-induced enhancement of synaptic plasticity in the PFC in the development of drug-associated behavioral plasticity. PMID:17050645

  16. Behavioral Regulation and the Modulation of Information Coding in the Lateral Prefrontal and Cingulate Cortex.

    PubMed

    Khamassi, Mehdi; Quilodran, René; Enel, Pierre; Dominey, Peter F; Procyk, Emmanuel

    2015-09-01

    To explain the high level of flexibility in primate decision-making, theoretical models often invoke reinforcement-based mechanisms, performance monitoring functions, and core neural features within frontal cortical regions. However, the underlying biological mechanisms remain unknown. In recent models, part of the regulation of behavioral control is based on meta-learning principles, for example, driving exploratory actions by varying a meta-parameter, the inverse temperature, which regulates the contrast between competing action probabilities. Here we investigate how complementary processes between lateral prefrontal cortex (LPFC) and dorsal anterior cingulate cortex (dACC) implement decision regulation during exploratory and exploitative behaviors. Model-based analyses of unit activity recorded in these 2 areas in monkeys first revealed that adaptation of the decision function is reflected in a covariation between LPFC neural activity and the control level estimated from the animal's behavior. Second, dACC more prominently encoded a reflection of outcome uncertainty useful for control regulation based on task monitoring. Model-based analyses also revealed higher information integration before feedback in LPFC, and after feedback in dACC. Overall the data support a role of dACC in integrating reinforcement-based information to regulate decision functions in LPFC. Our results thus provide biological evidence on how prefrontal cortical subregions may cooperate to regulate decision-making. PMID:24904073

  17. Rhinal and Dorsolateral Prefrontal Cortex Lesions Produce Selective Impairments in Object and Spatial Learning and Memory in Canines

    PubMed Central

    Christie, Lori-Ann; Saunders, Richard C.; Kowalska, Danuta, M.; MacKay, William A.; Head, Elizabeth; Cotman, Carl W.; Milgram, Norton W.

    2014-01-01

    To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed non-matching to sample, or DNMS) and a spatial (delayed non-matching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-sec delay, suggesting disrupted retention of the general task rules, however, this impairment was transient; long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a non-matching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals. PMID:18792072

  18. Category-dependent and category-independent goal-value codes in human ventromedial prefrontal cortex.

    PubMed

    McNamee, Daniel; Rangel, Antonio; O'Doherty, John P

    2013-04-01

    To choose between manifestly distinct options, it is suggested that the brain assigns values to goals using a common currency. Although previous studies have reported activity in ventromedial prefrontal cortex (vmPFC) correlating with the value of different goal stimuli, it remains unclear whether such goal-value representations are independent of the associated stimulus categorization, as required by a common currency. Using multivoxel pattern analyses on functional magnetic resonance imaging (fMRI) data, we found a region of medial prefrontal cortex to contain a distributed goal-value code that is independent of stimulus category. More ventrally in the vmPFC, we found spatially distinct areas of the medial orbitofrontal cortex to contain unique category-dependent distributed value codes for food and consumer items. These results implicate the medial prefrontal cortex in the implementation of a common currency and suggest a ventral versus dorsal topographical organization of value signals in the vmPFC. PMID:23416449

  19. Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

    PubMed Central

    Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

    2009-01-01

    ‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

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

    PubMed

    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. Hum Brain Mapp 37:896-912, 2016. © 2015 Wiley Periodicals, Inc. PMID:26663572

  1. Differential cognitive actions of norepinephrine a2 and a1 receptor signaling in the prefrontal cortex.

    PubMed

    Berridge, Craig W; Spencer, Robert C

    2016-06-15

    The prefrontal cortex (PFC) supports cognitive and behavioral processes that guide goal directed behavior. Moreover, dysregulated prefrontal cognitive dysfunction is associated with multiple psychiatric disorders. Norepinephrine (NE) signaling in the PFC is a critical modulator of prefrontal cognition and is targeted by a variety of drugs used to treat PFC-dependent cognitive dysfunction. Noradrenergic modulation of PFC-dependent cognition is complex, with concentration and receptor-specific actions that are likely dependent on neuronal activity state. Recent studies indicate that within the PFC, noradrenergic α1 and α2 receptors exert unique modulatory actions across distinct cognitive processes that allow for context-dependent modulation of cognition. Specifically, high affinity post-synaptic α2 receptors, engaged at moderate rates of NE release associated with moderate arousal levels, promote working memory. In contrast, lower affinity α1 receptors, engaged at higher rates of release associated with high arousal conditions (e.g. stress), impair working memory performance while promoting flexible attention. While these and other observations were initially interpreted to indicate high rates of NE release promotes the transition from focused to flexible/scanning attention, recent findings indicate that α1 receptors promote both focused and flexible attention. Collectively, these observations indicate that while α2 and α1 receptors in the PFC differentially modulate distinct cognitive processes, this cannot be simply ascribed to differential roles of these receptors in 'focused' vs. 'flexible' cognitive processes. Translationally, this information indicates that: (1) not all tests of prefrontal cognitive function may be appropriate for preclinical programs aimed at specific PFC-dependent disorders and (2) the treatment of specific PFC cognitive deficits may require the differential targeting of noradrenergic receptor subtypes. This article is part of a

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

    PubMed

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

    2016-02-15

    Postural instability represents a main source of disability in Parkinsonian syndromes and its pathophysiology is poorly understood. Indirect probes (i.e., mental imagery) of brain involvement support the role of prefrontal cortex as a key cortical region for postural control in older adults with and without Parkinsonian syndromes. Using functional near infrared spectroscopy (fNIRs) as a direct online cortical probe, this study aimed to compare neural activation patterns in prefrontal cortex, postural stability, and their respective interactions, in (1) patients with Parkinsonian syndromes; (2) those with mild parkinsonian signs; (3) and healthy older adults. Among 269 non-demented older adults (76.41 ± 6.70 years, 56% women), 26 individuals presented with Parkinsonian syndromes (Unified Parkinson's disease rating scale (UPDRS): 11.08 ± 3.60), 117 had mild parkinsonian signs (UPDRS: 3.21 ± 2.49), and 126 individuals were included as a healthy control group. Participants were asked to stand upright and count silently for ten seconds while changes in oxygenated hemoglobin levels over prefrontal cortex were measured using fNIRs. We simultaneously evaluated postural stability with center of pressure velocity data recorded on an instrumented walkway. Compared to healthy controls and patients with mild parkinsonian signs, patients with Parkinsonian syndromes demonstrated significantly higher prefrontal oxygenation levels to maintain postural stability. The pattern of brain activation and postural control of participants with mild parkinsonian signs were similar to that of normal controls. These findings highlight the online role of the prefrontal cortex in postural control in patients with Parkinsonian syndromes and afford the opportunity to improve therapeutic options for postural instability. PMID:26551767

  3. Oxidant/antioxidant effects of chronic exposure to predator odor in prefrontal cortex, amygdala, and hypothalamus.

    PubMed

    Mejia-Carmona, G E; Gosselink, K L; Pérez-Ishiwara, G; Martínez-Martínez, A

    2015-08-01

    The incidence of anxiety-related diseases is increasing these days, hence there is a need to understand the mechanisms that underlie its nature and consequences. It is known that limbic structures, mainly the prefrontal cortex and amygdala, are involved in the processing of anxiety, and that projections from prefrontal cortex and amygdala can induce activity of the hypothalamic-pituitary-adrenal axis with consequent cardiovascular changes, increase in oxygen consumption, and ROS production. The compensatory reaction can include increased antioxidant enzymes activities, overexpression of antioxidant enzymes, and genetic shifts that could include the activation of antioxidant genes. The main objective of this study was to evaluate the oxidant/antioxidant effect that chronic anxiogenic stress exposure can have in prefrontal cortex, amygdala, and hypothalamus by exposition to predator odor. Results showed (a) sensitization of the HPA axis response, (b) an enzymatic phase 1 and 2 antioxidant response to oxidative stress in amygdala, (c) an antioxidant stability without elevation of oxidative markers in prefrontal cortex, (d) an elevation in phase 1 antioxidant response in hypothalamus. Chronic exposure to predator odor has an impact in the metabolic REDOX state in amygdala, prefrontal cortex, and hypothalamus, with oxidative stress being prevalent in amygdala as this is the principal structure responsible for the management of anxiety. PMID:25981530

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Effects of Mandibular Retrusive Deviation on Prefrontal Cortex Activation: A Functional Near-Infrared Spectroscopy Study

    PubMed Central

    Otsuka, Takero; Yamasaki, Ryuichi; Shimazaki, Tateshi; Sasaguri, Kenichi; Kawata, Toshitsugu

    2015-01-01

    The objective of this study was to evaluate occlusal condition by assessing brain activity in the prefrontal cortex, which is associated with emotion. Functional near-infrared spectroscopy (fNIRS) was used to detect changes in cerebral blood flow in the prefrontal cortex of 12 healthy volunteers. The malocclusion model was a custom-made splint that forced the mandible into retrusion. A splint with no modification was used as a control. The cortical activation during clenching was compared between the retrusive position condition and the control condition. A visual analog scale score for discomfort was also obtained during clenching and used to evaluate the interaction between fNIRS data and psychiatric changes. Activation of the prefrontal cortex was significantly greater during clenching in the mandibular retrusive condition than during clenching in the control condition. Furthermore, Spearman rank-correlation coefficient revealed a parallel relation between prefrontal cortex activation and visual analog scale score for discomfort. These results indicate that fNIRS can be used to objectively evaluate the occlusal condition by evaluating activity in the prefrontal cortex. PMID:26075235

  6. Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum.

    PubMed

    Jarbo, Kevin; Verstynen, Timothy D

    2015-03-01

    Modification of spatial attention via reinforcement learning (Lee and Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander et al., 1986), but locally overlapping (Haber, 2003), topographical organization. Here we explore whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N = 60) was used to map frontostriatal and parietostriatal projections. In general, projections from cortex were organized according to both a medial-lateral and a rostral-caudal gradient along the striatal nuclei. Within rostral aspects of the striatum, we identified two bilateral convergence zones (one in the caudate nucleus and another in the putamen) that consisted of voxels with unique projections from orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data, in which a high percentage of structurally connected voxels also showed significant functional connectivity. The specificity of this convergent architecture to these regions of the rostral striatum was validated against control analysis of connectivity within the motor putamen. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning. PMID:25740516

  7. Converging Structural and Functional Connectivity of Orbitofrontal, Dorsolateral Prefrontal, and Posterior Parietal Cortex in the Human Striatum

    PubMed Central

    Jarbo, Kevin

    2015-01-01

    Modification of spatial attention via reinforcement learning (Lee and Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander et al., 1986), but locally overlapping (Haber, 2003), topographical organization. Here we explore whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N = 60) was used to map frontostriatal and parietostriatal projections. In general, projections from cortex were organized according to both a medial–lateral and a rostral–caudal gradient along the striatal nuclei. Within rostral aspects of the striatum, we identified two bilateral convergence zones (one in the caudate nucleus and another in the putamen) that consisted of voxels with unique projections from orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data, in which a high percentage of structurally connected voxels also showed significant functional connectivity. The specificity of this convergent architecture to these regions of the rostral striatum was validated against control analysis of connectivity within the motor putamen. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning. PMID:25740516

  8. Preferential encoding of visual categories in parietal cortex compared with prefrontal cortex.

    PubMed

    Swaminathan, Sruthi K; Freedman, David J

    2012-02-01

    The ability to recognize the behavioral relevance, or category membership, of sensory stimuli is critical for interpreting the meaning of events in our environment. Neurophysiological studies of visual categorization have found categorical representations of stimuli in prefrontal cortex (PFC), an area that is closely associated with cognitive and executive functions. Recent studies have also identified neuronal category signals in parietal areas that are typically associated with visual-spatial processing. It has been proposed that category-related signals in parietal cortex and other visual areas may result from 'top-down' feedback from PFC. We directly compared neuronal activity in the lateral intraparietal (LIP) area and PFC in monkeys performing a visual motion categorization task. We found that LIP showed stronger, more reliable and shorter latency category signals than PFC. These findings suggest that LIP is strongly involved in visual categorization and argue against the idea that parietal category signals arise as a result of feedback from PFC during this task. PMID:22246435

  9. Amygdala Perfusion Is Predicted by Its Functional Connectivity with the Ventromedial Prefrontal Cortex and Negative Affect

    PubMed Central

    Coombs III, Garth; Loggia, Marco L.; Greve, Douglas N.; Holt, Daphne J.

    2014-01-01

    Background Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states. Methods Here we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects. Results BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety. Conclusions These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach. PMID:24816735

  10. Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells

    PubMed Central

    Massart, Renaud; Dymov, Sergiy; Millecamps, Magali; Suderman, Matthew; Gregoire, Stephanie; Koenigs, Kevin; Alvarado, Sebastian; Tajerian, Maral; Stone, Laura S.; Szyf, Moshe

    2016-01-01

    We tested the hypothesis that epigenetic mechanisms in the brain and the immune system are associated with chronic pain. Genome-wide DNA methylation assessed in 9 months post nerve-injury (SNI) and Sham rats, in the prefrontal cortex (PFC) as well as in T cells revealed a vast difference in the DNA methylation landscape in the brain between the groups and a remarkable overlap (72%) between differentially methylated probes in T cells and prefrontal cortex. DNA methylation states in the PFC showed robust correlation with pain score of animals in several genes involved in pain. Finally, only 11 differentially methylated probes in T cells were sufficient to distinguish SNI or Sham individual rats. This study supports the plausibility of DNA methylation involvement in chronic pain and demonstrates the potential feasibility of DNA methylation markers in T cells as noninvasive biomarkers of chronic pain susceptibility. PMID:26817950

  11. Successful face recognition is associated with increased prefrontal cortex activation in autism spectrum disorder.

    PubMed

    Herrington, John D; Riley, Meghan E; Grupe, Daniel W; Schultz, Robert T

    2015-04-01

    This study examines whether deficits in visual information processing in autism-spectrum disorder (ASD) can be offset by the recruitment of brain structures involved in selective attention. During functional MRI, 12 children with ASD and 19 control participants completed a selective attention one-back task in which images of faces and houses were superimposed. When attending to faces, the ASD group showed increased activation relative to control participants within multiple prefrontal cortex areas, including dorsolateral prefrontal cortex (DLPFC). DLPFC activation in ASD was associated with increased response times for faces. These data suggest that prefrontal cortex activation may represent a compensatory mechanism for diminished visual information processing abilities in ASD. PMID:25234479

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

    PubMed

    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. PMID:21338690

  13. Monogamous and promiscuous rodent species exhibit discrete variation in the size of the medial prefrontal cortex.

    PubMed

    Kingsbury, Marcy A; Gleason, Erin D; Ophir, Alexander G; Phelps, Steven M; Young, Larry J; Marler, Catherine A

    2012-01-01

    Limbic-associated cortical areas, such as the medial prefrontal and retrosplenial cortex (mPFC and RS, respectively), are involved in the processing of emotion, motivation, and various aspects of working memory and have been implicated in mating behavior. To determine whether the independent evolution of mating systems is associated with a convergence in cortical mechanisms, we compared the size of mPFC and RS between the monogamous prairie vole (Microtus ochrogaster) and the promiscuous meadow vole (Microtus pennsylvanicus), and between the monogamous California mouse (Peromyscus californicus) and the promiscuous white-footed mouse (Peromyscus leucopus). For both promiscuous mice and voles, the mPFC occupied a significantly larger percentage of total cortex than in the monogamous species. No significant differences were observed for the RS or overall cortex size with respect to mating system, supporting the convergent evolution of mPFC size, specifically. Individual differences in the mating behavior of male prairie voles (wandering versus pair-bonding), presumably facultative tactics, were not reflected in the relative size of the mPFC, which is likely a heritable trait. Given the importance of the mPFC for complex working memory, particularly object-place and temporal order memory, we hypothesize that the relatively greater size of the mPFC in promiscuous species reflects a greater need to remember multiple individuals and the times and locations in which they have been encountered in the home range. PMID:22759599

  14. Medial prefrontal cortex-dorsal anterior cingulate cortex connectivity during behavior selection without an objective correct answer.

    PubMed

    Nakao, Takashi; Osumi, Takahiro; Ohira, Hideki; Kasuya, Yukinori; Shinoda, Jun; Yamada, Jitsuhiro; Northoff, Georg

    2010-10-01

    Life choices (e.g., occupational choice) often include situations with two or more possible correct answers, thereby putting us in a situation of conflict. Recent reports have described that the evaluation of conflict might be crucially mediated by neural activity in the dorsal anterior cingulate cortex (dACC), although the reduction of conflict might rather be associated with neural activity in the medial prefrontal cortex (MPFC). What remains unclear is whether these regions mutually interact, thereby raising the question of their functional connectivity during conflict situations. Using psychophysiological interaction (PPI) analyses of functional magnetic resonance imaging (fMRI) data, this study shows that the dACC co-varied significantly higher with the MPFC during an occupational choice task with two possible correct answers when compared to the control task: a word-length task with one possible correct answer. These results suggest that the MPFC has a functional relation with dACC, especially in conflict situations where there is no objective correct answer. Taken together, this lends support to the assumption that the MPFC might be crucial in biasing the decision, thereby reducing conflict. PMID:20655361

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

    PubMed

    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. PMID:27033686

  16. Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex

    PubMed Central

    Hussey, Erika K.; Ward, Nathan; Christianson, Kiel; Kramer, Arthur F.

    2015-01-01

    Recent research demonstrates that performance on executive-control measures can be enhanced through brain stimulation of lateral prefrontal regions. Separate psycholinguistic work emphasizes the importance of left lateral prefrontal cortex executive-control resources during sentence processing, especially when readers must override early, incorrect interpretations when faced with temporary ambiguity. Using transcranial direct current stimulation, we tested whether stimulation of left lateral prefrontal cortex had discriminate effects on language and memory conditions that rely on executive-control (versus cases with minimal executive-control demands, even in the face of task difficulty). Participants were randomly assigned to receive Anodal, Cathodal, or Sham stimulation of left lateral prefrontal cortex while they (1) processed ambiguous and unambiguous sentences in a word-by-word self-paced reading task and (2) performed an n-back memory task that, on some trials, contained interference lure items reputed to require executive-control. Across both tasks, we parametrically manipulated executive-control demands and task difficulty. Our results revealed that the Anodal group outperformed the remaining groups on (1) the sentence processing conditions requiring executive-control, and (2) only the most complex n-back conditions, regardless of executive-control demands. Together, these findings add to the mounting evidence for the selective causal role of left lateral prefrontal cortex for executive-control tasks in the language domain. Moreover, we provide the first evidence suggesting that brain stimulation is a promising method to mitigate processing demands encountered during online sentence processing. PMID:26528814

  17. Recency gets larger as lesions move from anterior to posterior locations within the ventromedial prefrontal cortex.

    PubMed

    Hochman, Guy; Yechiam, Eldad; Bechara, Antoine

    2010-11-12

    In the past two decades neuroimaging research has substantiated the important role of the prefrontal cortex (PFC) in decision-making. In the current study, we use the complementary lesion based approach to deepen our knowledge concerning the specific cognitive mechanisms modulated by prefrontal activity. Specifically, we assessed the brain substrates implicated in two decision making dimensions in a sample of prefrontal cortex patients: (a) the tendency to differently weigh recent compared to past experience; and (b) the tendency to differently weigh gains compared to losses. The participants performed the Iowa Gambling Task, a complex experience-based decision-making task, which was analyzed with a formal cognitive model (the Expectancy-Valance model). The results indicated that decisions become influenced by more recent, as opposed to older, events when the damage reaches the posterior sectors of the ventromedial prefrontal cortex (VMPC). Furthermore, the degree of this recency deficit was related to the size of the lesion. These results suggest that the posterior area of the prefrontal cortex directly modulates the capacity to use time-delayed information. In contrast, we did not find similar modulation for the sensitivity to gains versus losses. PMID:20412820

  18. Generalisation benefits of output gating in a model of prefrontal cortex

    NASA Astrophysics Data System (ADS)

    Kriete, Trent; Noelle, David C.

    2011-06-01

    The prefrontal cortex (PFC) plays a central role in flexible cognitive control, including the suppression of habitual responding in favour of situation-appropriate behaviours that can be quite novel. PFC provides a kind of working memory, maintaining the rules, goals, and/or actions that are to control behaviour in the current context. For flexible control, these PFC representations must be sufficiently componential to support systematic generalisation to novel situations. The anatomical structure of PFC can be seen as implementing a componential 'slot-filler' structure, with different components encoded over isolated pools of neurons. Previous PFC models have highlighted the importance of a dynamic gating mechanism to selectively update individual 'slot' contents. In this article, we present simulation results that suggest that systematic generalisation also requires an 'output gating' mechanism that limits the influence of PFC on more posterior brain areas to reflect a small number of representational components at any one time.

  19. Orbital prefrontal cortex volume predicts social network size: an imaging study of individual differences in humans

    PubMed Central

    Powell, Joanne; Lewis, Penelope A.; Roberts, Neil; García-Fiñana, Marta; Dunbar, R. I. M.

    2012-01-01

    The social brain hypothesis, an explanation for the unusually large brains of primates, posits that the size of social group typical of a species is directly related to the volume of its neocortex. To test whether this hypothesis also applies at the within-species level, we applied the Cavalieri method of stereology in conjunction with point counting on magnetic resonance images to determine the volume of prefrontal cortex (PFC) subfields, including dorsal and orbital regions. Path analysis in a sample of 40 healthy adult humans revealed a significant linear relationship between orbital (but not dorsal) PFC volume and the size of subjects' social networks that was mediated by individual intentionality (mentalizing) competences. The results support the social brain hypothesis by indicating a relationship between PFC volume and social network size that applies within species, and, more importantly, indicates that the relationship is mediated by social cognitive skills. PMID:22298855

  20. Testing the involvement of the prefrontal cortex in lucid dreaming: a tDCS study.

    PubMed

    Stumbrys, Tadas; Erlacher, Daniel; Schredl, Michael

    2013-12-01

    Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed. PMID:24021850

  1. Neural correlates of depth of strategic reasoning in medial prefrontal cortex

    PubMed Central

    Coricelli, Giorgio; Nagel, Rosemarie

    2009-01-01

    We used functional MRI (fMRI) to investigate human mental processes in a competitive interactive setting—the “beauty contest” game. This game is well-suited for investigating whether and how a player's mental processing incorporates the thinking process of others in strategic reasoning. We apply a cognitive hierarchy model to classify subject's choices in the experimental game according to the degree of strategic reasoning so that we can identify the neural substrates of different levels of strategizing. According to this model, high-level reasoners expect the others to behave strategically, whereas low-level reasoners choose based on the expectation that others will choose randomly. The data show that high-level reasoning and a measure of strategic IQ (related to winning in the game) correlate with the neural activity in the medial prefrontal cortex, demonstrating its crucial role in successful mentalizing. This supports a cognitive hierarchy model of human brain and behavior. PMID:19470476

  2. Catecholamine receptors differentially mediate impulsive choice in the medial prefrontal and orbitofrontal cortex.

    PubMed

    Pardey, Margery C; Kumar, Natasha N; Goodchild, Ann K; Cornish, Jennifer L

    2013-02-01

    Impulsivity is characteristic of several mental health disorders and is largely mediated by the prefrontal cortex subregions: the medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC). Dopamine (DA) and norepinephrine (NE) are known to modulate activity of the prefrontal cortex, however their direct role in impulsive choice is not known. The aim of the present study was to investigate the effect of microinjecting DA or NE compounds in the mPFC or OFC on impulsive choice as measured by a delayed reinforcement (DR) task in male Wistar Kyoto rats. Following training in the DR task, rats were pretreated with DA D(1) and D(2) receptor antagonists (SCH23390 3 μg/side, raclopride 3 or 6 μg/side) or NE α(1) and α(2) receptor agonists (phenylephrine 0.1 or 0.3 μg/side, guanfacine 1 or 3 μg/side, respectively) into the mPFC or OFC and the effect on impulsive behavior was assessed. Pretreatment with raclopride into the mPFC or OFC significantly increased impulsive choice, however only pretreatment with SCH23390 into the mPFC, and not the OFC, significantly increased impulsive choice. Pretreatment with the NE receptor agonists had no effect on impulsive choice. This study suggests that DA receptors, but not NE receptors, differentially mediate impulsive choice in sub-regions of the prefrontal cortex. PMID:23135240

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

    PubMed

    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. PMID:25956033

  4. Mindfulness training modulates value signals in ventromedial prefrontal cortex through input from insular cortex

    PubMed Central

    Kirk, Ulrich; Gu, Xiaosi; Harvey, Ann H.; Fonagy, Peter; Montague, P. Read

    2014-01-01

    Neuroimaging research has demonstrated that ventromedial prefrontal cortex (vmPFC) encodes value signals that can be modulated by top-down cognitive input such as semantic knowledge, price incentives, and monetary favors suggesting that such biases may have an identified biological basis. It has been hypothesized that mindfulness training (MT) provides one path for gaining control over such top-down influences; yet, there have been no direct tests of this hypothesis. Here, we probe the behavioral and neural effects of MT on value signals in vmPFC in a randomized longitudinal design of 8 weeks of MT on an initially naïve subject cohort. The impact of this within-subject training was assessed using two paradigms: one that employed primary rewards (fruit juice) in a simple conditioning task and another that used a well-validated art-viewing paradigm to test bias of monetary favors on preference. We show that MT behaviorally censors the top-down bias of monetary favors through a measurable influence on value signals in vmPFC. MT also modulates value signals in vmPFC to primary reward delivery. Using a separate cohort of subjects we show that 8 weeks of active control training (ACT) generates the same behavioral impact also through an effect on signals in the vmPFC. Importantly, functional connectivity analyses show that value signals in vmPFC are coupled with bilateral posterior insula in the MT groups in both paradigms, but not in the ACT groups. These results suggest that MT integrates interoceptive input from insular cortex in the context of value computations of both primary and secondary rewards. PMID:24956066

  5. Autonomous encoding of irrelevant goals and outcomes by prefrontal cortex neurons.

    PubMed

    Genovesio, Aldo; Tsujimoto, Satoshi; Navarra, Giulia; Falcone, Rossella; Wise, Steven P

    2014-01-29

    Two rhesus monkeys performed a distance discrimination task in which they reported whether a red square or a blue circle had appeared farther from a fixed reference point. Because a new pair of distances was chosen randomly on each trial, and because the monkeys had no opportunity to correct errors, no information from the previous trial was relevant to a current one. Nevertheless, many prefrontal cortex neurons encoded the outcome of the previous trial on current trials. A smaller, intermingled population of cells encoded the spatial goal on the previous trial or the features of the chosen stimuli, such as color or shape. The coding of previous outcomes and goals began at various times during a current trial, and it was selective in that prefrontal cells did not encode other information from the previous trial. The monitoring of previous goals and outcomes often contributes to problem solving, and it can support exploratory behavior. The present results show that such monitoring occurs autonomously and selectively, even when irrelevant to the task at hand. PMID:24478376

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

    PubMed Central

    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

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

    PubMed

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

    2015-09-01

    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

  8. Effects of blood flow to the prefrontal cortex on high-intensity exercise combined with high-decibel music.

    PubMed

    Chang, Hyukki; Kim, Kyungae; Jung, Yu-Jin; Ahn, Na-Ri; So, Wi-Young; Kato, Morimasa

    2013-12-01

    We studied the effects of high-intensity exercise (70-75% of VO2 max) combined with high-decibel music (100 dB) on cognitive function (measured by the Stroop test) and related blood flow changes to the prefrontal cortex (measured by Oxy-hemoglobin (Hb), Deoxy-Hb, tissue oxygen index (TOI), and normalized tissue hemoglobin index (nTHI)). The subjects of the study were 28 healthy female university students in their early 20s. Subjects were categorized into control group (CG), music group (MG), exercise group (Ex), and music and exercise group (MnEx). A crossover design was implemented so that all subjects participated in all test groups. We found no significant difference in reaction time between CG and MG for the neutral and incongruent tasks of Stroop test. However, there were significant improvements in the neutral and incongruent tasks for both the Ex (p < 0.01) and MnEx (p < 0.01) groups. Oxy-Hb measurements in the prefrontal cortex of the brain supported the Stroop test data. We found no difference between Ex and MnEx in the TOI; however, there was a significant decrease (p < 0.05) in MnEx compared to Ex. In addition, Ex resulted in a significant increase (p < 0.05) in nTHI as compared to CG. These results indicate that high decibel music could negatively affect prefrontal cortex activation of the brain during exercise. PMID:25566422

  9. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory.

    PubMed

    Lapish, Christopher C; Balaguer-Ballester, Emili; Seamans, Jeremy K; Phillips, Anthony G; Durstewitz, Daniel

    2015-07-15

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. PMID:26180194

  10. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

    PubMed Central

    Balaguer-Ballester, Emili; Seamans, Jeremy K.; Phillips, Anthony G.; Durstewitz, Daniel

    2015-01-01

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. PMID:26180194

  11. Hippocampal-prefrontal input supports spatial encoding in working memory

    PubMed Central

    Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E.; Fusi, Stefano; Gogos, Joseph A.; Gordon, Joshua A.

    2015-01-01

    Summary Spatial working memory, the caching of behaviorally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. While the prefrontal cortex and hippocampus are known to jointly contribute to successful spatial working memory, the anatomical pathway and temporal window for interaction of these structures critical to spatial working memory has not yet been established. Here, we find that direct hippocampal-prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal-prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory. PMID:26053122

  12. Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats

    PubMed Central

    2012-01-01

    Background There has been an increasing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system, we performed microarray-based global gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Results Following pathway analysis and validation of gene lists by real-time polymerase chain reaction, 30 genes from the hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase C gamma and epsilon, ABCA1 (ATP-Binding Cassette A1), CD47 (Cluster of Differentiation 47) and the RET (Rearranged During Transfection) protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipid metabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus striatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. Conclusions According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3 diabetes. PMID:22369239

  13. Early detection and late cognitive control of emotional distraction by the prefrontal cortex

    PubMed Central

    García-Pacios, Javier; Garcés, Pilar; Del Río, David; Maestú, Fernando

    2015-01-01

    Unpleasant emotional distraction can impair the retention of non-emotional information in working memory (WM). Research links the prefrontal cortex with the successful control of such biologically relevant distractors, although the temporal changes in this brain mechanism remain unexplored. We use magnetoencephalography to investigate the temporal dynamics of the cognitive control of both unpleasant and pleasant distraction, in the millisecond (ms) scale. Behavioral results demonstrate that pleasant events do not affect WM maintenance more than neutral ones. Neuroimaging results show that prefrontal cortices are recruited for the rapid detection of emotional distraction, at early latencies of the processing (70-130 ms). Later in the processing (360-450 ms), the dorsolateral, the medial and the orbital sections of the prefrontal cortex mediate the effective control of emotional distraction. In accordance with the behavioral performance, pleasant distractors do not require higher prefrontal activity than neutral ones. These findings extend our knowledge about the brain mechanisms of coping with emotional distraction in WM. In particular, they show for the first time that overriding the attentional capture triggered by emotional distractors, while maintaining task-relevant elements in mind, is based on the early detection of such linked-to-survival information and on its later cognitive control by the prefrontal cortex. PMID:26067780

  14. Lower neuronal variability in the monkey dorsolateral prefrontal than posterior parietal cortex.

    PubMed

    Qi, Xue-Lian; Constantinidis, Christos

    2015-10-01

    The dorsolateral prefrontal and posterior parietal cortex are two brain areas involved in cognitive functions such as spatial attention and working memory. When tested with identical tasks, only subtle differences in firing rate are present between neurons recorded in the two areas. In this article we report that major differences in neuronal variability characterize the two areas during working memory. The Fano factors of spike counts in dorsolateral prefrontal neurons were consistently lower than those of the posterior parietal cortex across a range of tasks, epochs, and conditions in the same monkeys. Variability differences were observed despite minor differences in firing rates between the two areas in the tasks tested and higher overall firing rate in the prefrontal than in the posterior parietal sample. Other measures of neuronal discharge variability, such as the coefficient of variation of the interspike interval, displayed the same pattern of lower prefrontal variability. Fano factor values were negatively correlated with performance in the working memory task, suggesting that higher neuronal variability was associated with diminished task performance. The results indicate that information involving remembered stimuli is more reliably represented in the prefrontal than the posterior parietal cortex based on the variability of neuronal responses, and suggest functional differentiation between the two areas beyond differences in firing rate. PMID:26269556

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

    PubMed

    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. PMID:8614521

  16. Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex

    PubMed Central

    Ray, Rebecca; Zald, David H.

    2011-01-01

    Ray, R. and D. Zald. Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex. NEUROSCI BIOBEHAV REV 36(X) XXX-XXX, 2011. -Psychological research increasingly indicates that emotional processes interact with other aspects of cognition. Studies have demonstrated both the ability of emotional stimuli to influence a broad range of cognitive operations, and the ability of humans to use top-down cognitive control mechanisms to regulate emotional responses. Portions of the prefrontal cortex appear to play a significant role in these interactions. However, the manner in which these interactions are implemented remains only partially elucidated. In the present review we describe the anatomical connections between ventral and dorsal prefrontal areas as well as their connections with limbic regions. Only a subset of prefrontal areas are likely to directly influence amygdalar processing, and as such models of prefrontal control of emotions and models of emotional regulation should be constrained to plausible pathways of influence. We also focus on how the specific pattern of feedforward and feedback connections between these regions may dictate the nature of information flow between ventral and dorsal prefrontal areas and the amygdala. These patterns of connections are inconsistent with several commonly expressed assumptions about the nature of communications between emotion and cognition. PMID:21889953

  17. Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function

    PubMed Central

    Butts, Kelly A.; Weinberg, Joanne; Young, Allan H.; Phillips, Anthony G.

    2011-01-01

    Enhanced dopamine efflux in the prefrontal cortex is a well-documented response to acute stress. However, the underlying mechanism(s) for this response is unknown. Using in vivo microdialysis, we demonstrate that blocking glucocorticoid receptors locally within the rat prefrontal cortex results in a reduction in stress-evoked dopamine efflux. In contrast, blocking glucocorticoid receptors in the ventral tegmental area did not affect stress-evoked dopamine efflux in the prefrontal cortex. Additionally, local administration of corticosterone into the prefrontal cortex increased prefrontal dopamine efflux. The functional impact of enhanced dopamine efflux evoked by acute stress was demonstrated using a cognitive task dependent on the prefrontal cortex and sensitive to impairment in working memory. Notably, stress-induced impairments in cognition were attenuated by blockade of glucocorticoid receptors in the prefrontal cortex. Taken together, these data demonstrate that glucocorticoids act locally within the prefrontal cortex to modulate mesocortical dopamine efflux leading to the cognitive impairments observed during acute stress. PMID:22032926

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

    NASA Technical Reports Server (NTRS)

    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

  19. Prefrontal cortex and executive function in young children: a review of NIRS studies

    PubMed Central

    Moriguchi, Yusuke; Hiraki, Kazuo

    2013-01-01

    Executive function (EF) refers to the higher-order cognitive control process for the attainment of a specific goal. There are several subcomponents of EF, such as inhibition, cognitive shifting, and working memory. Extensive neuroimaging research in adults has revealed that the lateral prefrontal cortex plays an important role in EF. Developmental studies have reported behavioral evidence showing that EF changes significantly during preschool years. However, the neural mechanism of EF in young children is still unclear. This article reviews recent near-infrared spectroscopy (NIRS) research that examined the relationship between the development of EF and the lateral prefrontal cortex. Specifically, this review focuses on inhibitory control, cognitive shifting, and working memory in young children. Research has consistently shown significant prefrontal activation during tasks in typically developed children, but this activation may be abnormal in children with developmental disorders. Finally, methodological issues and future directions are discussed. PMID:24381551

  20. Exercise-induced stress resistance is independent of exercise controllability and the medial prefrontal cortex.

    PubMed

    Greenwood, Benjamin N; Spence, Katie G; Crevling, Danielle M; Clark, Peter J; Craig, Wendy C; Fleshner, Monika

    2013-02-01

    Exercise increases resistance against stress-related disorders such as anxiety and depression. Similarly, the perception of control is a powerful predictor of neurochemical and behavioral responses to stress, but whether the experience of choosing to exercise, and exerting control over that exercise, is a critical factor in producing exercise-induced stress resistance is unknown. The current studies investigated whether the protective effects of exercise against the anxiety- and depression-like consequences of stress are dependent on exercise controllability and a brain region implicated in the protective effects of controllable experiences, the medial prefrontal cortex. Adult male Fischer 344 rats remained sedentary, were forced to run on treadmills or motorised running wheels, or had voluntary access to wheels for 6 weeks. Three weeks after exercise onset, rats received sham surgery or excitotoxic lesions of the medial prefrontal cortex. Rats were exposed to home cage or uncontrollable tail shock treatment three weeks later. Shock-elicited fear conditioning and shuttle box escape testing occurred the next day. Both forced and voluntary wheel running, but not treadmill training, prevented the exaggerated fear conditioning and interference with escape learning produced by uncontrollable stress. Lesions of the medial prefrontal cortex failed to eliminate the protective effects of forced or voluntary wheel running. These data suggest that exercise controllability and the medial prefrontal cortex are not critical factors in conferring the protective effects of exercise against the affective consequences of stressor exposure, and imply that exercise perceived as forced may still benefit affect and mental health. PMID:23121339

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  2. Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

    ERIC Educational Resources Information Center

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    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…

  3. Orbital and Ventromedial Prefrontal Cortex Functioning in Parkinson's Disease: Neuropsychological Evidence

    ERIC Educational Resources Information Center

    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…

  4. Prefrontal Cortex Lesions and Sex Differences in Fear Extinction and Perseveration

    ERIC Educational Resources Information Center

    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…

  5. Hippocampal Train Stimulation Modulates Recall of Fear Extinction Independently of Prefrontal Cortex Synaptic Plasticity and Lesions

    ERIC Educational Resources Information Center

    Garcia, Rene; Farinelli, Melissa; Deschaux, Olivier; Hugues, Sandrine; Thevenet, Aurelie

    2006-01-01

    It has been shown that long-term potentiation (LTP) develops in the connection between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) and between the hippocampus (HPC) and the mPFC following fear extinction, and correlates with extinction retention. However, recent lesion studies have shown that combined lesions of the MD…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  7. The Medial Prefrontal Cortex Is Critical for Memory Retrieval and Resolving Interference

    ERIC Educational Resources Information Center

    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…

  8. MEDIAL PREFRONTAL CORTEX LESIONS AND SPATIAL DELAYED ALTERNATION IN THE RAT: RECOVERY OR SPARING?

    EPA Science Inventory

    In Experiment 1, Long-Evans rat pups received medial prefrontal cortex (PFC) aspirations or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform one of two T-maze tasks: iscrete-trials delayed alternation (DA) or simple position discrimination (PD). ...

  9. Noradrenergic Action in Prefrontal Cortex in the Late Stage of Memory Consolidation

    ERIC Educational Resources Information Center

    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…

  10. Reduced Prefrontal Cortex Hemodynamic Response in Adults with Methamphetamine Induced Psychosis: Relevance for Impulsivity.

    PubMed

    Yamamuro, Kazuhiko; Kimoto, Sohei; Iida, Junzo; Kishimoto, Naoko; Nakanishi, Yoko; Tanaka, Shohei; Ota, Toyosaku; Makinodan, Manabu; Kishimoto, Toshifumi

    2016-01-01

    Patients with methamphetamine abuse/dependence often exhibit high levels of impulsivity, which may be associated with the structural abnormalities and functional hypoactivities observed in the frontal cortex of these subjects. Although near-infrared spectroscopy (NIRS) is a simple and non-invasive method for characterizing the clinical features of various psychiatric illnesses, few studies have used NIRS to directly investigate the association between prefrontal cortical activity and inhibitory control in patients with methamphetamine-induced psychosis (MAP). Using a 24-channel NIRS system, we compared hemodynamic responses during the Stroop color-word task in 14 patients with MAP and 21 healthy controls matched for age, sex and premorbid IQ. In addition, we used the Barrett Impulsivity Scale-11 (BIS-11) to assess impulsivity between subject groups. The MAP group exhibited significantly less activation in the anterior and frontopolar prefrontal cortex accompanied by lower Stroop color-word task performance, compared with controls. Moreover, BIS-11 scores were significantly higher in the MAP group, and were negatively correlated with the hemodynamic responses in prefrontal cortex. Our data suggest that reduced hemodynamic responses in the prefrontal cortex might reflect higher levels of impulsivity in patients with MAP, providing new insights into disrupted inhibitory control observed in MAP. PMID:27050450

  11. Disruption of the Perineuronal Net in the Hippocampus or Medial Prefrontal Cortex Impairs Fear Conditioning

    ERIC Educational Resources Information Center

    Hylin, Michael J.; Orsi, Sara A.; Moore, Anthony N.; Dash, Pramod K.

    2013-01-01

    The perineuronal net (PNN) surrounds neurons in the central nervous system and is thought to regulate developmental plasticity. A few studies have shown an involvement of the PNN in hippocampal plasticity and memory storage in adult animals. In addition to the hippocampus, plasticity in the medial prefrontal cortex (mPFC) has been demonstrated to…

  12. Prefrontal Cortex and Hippocampus Subserve Different Components of Working Memory in Rats

    ERIC Educational Resources Information Center

    Yoon, Taejib; Okada, Jeffrey; Jung, Min W.; Kim, Jeansok J.

    2008-01-01

    Both the medial prefrontal cortex (mPFC) and hippocampus are implicated in working memory tasks in rodents. Specifically, it has been hypothesized that the mPFC is primarily engaged in the temporary storage and processing of information lasting from a subsecond to several seconds, while the hippocampal function becomes more critical as the working…

  13. Hippocampus and Medial Prefrontal Cortex Contributions to Trace and Contextual Fear Memory Expression over Time

    ERIC Educational Resources Information Center

    Beeman, Christopher L.; Bauer, Philip S.; Pierson, Jamie L.; Quinn, Jennifer J.

    2013-01-01

    Previous work has shown that damage to the dorsal hippocampus (DH) occurring at recent, but not remote, timepoints following acquisition produces a deficit in trace conditioned fear memory expression. The opposite pattern has been observed with lesions to the medial prefrontal cortex (mPFC). The present studies address: (1) whether these lesion…

  14. The Neuropsychology of Ventral Prefrontal Cortex: Decision-Making and Reversal Learning

    ERIC Educational Resources Information Center

    Clark, L.; Cools, R.; Robbins, T. W.

    2004-01-01

    Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that…

  15. Performance-Related Activity in Medial Rostral Prefrontal Cortex (Area 10) during Low-Demand Tasks

    ERIC Educational Resources Information Center

    Gilbert, Sam J.; Simons, Jon S.; Frith, Christopher D.; Burgess, Paul W.

    2006-01-01

    Neuroimaging studies have frequently observed relatively high activity in medial rostral prefrontal cortex (PFC) during rest or baseline conditions. Some accounts have attributed this high activity to the occurrence of unconstrained stimulus-independent and task-unrelated thought processes during baseline conditions. Here, the authors investigated…

  16. Medial Prefrontal Cortex Is Selectively Involved in Response Selection Using Visual Context in the Background

    ERIC Educational Resources Information Center

    Lee, Inah; Shin, Ji Yun

    2012-01-01

    The exact roles of the medial prefrontal cortex (mPFC) in conditional choice behavior are unknown and a visual contextual response selection task was used for examining the issue. Inactivation of the mPFC severely disrupted performance in the task. mPFC inactivations, however, did not disrupt the capability of perceptual discrimination for visual…

  17. Selection for Position: The Role of Left Ventrolateral Prefrontal Cortex in Sequencing Language

    ERIC Educational Resources Information Center

    Thothathiri, Malathi; Schwartz, Myrna F.; Thompson-Schill, Sharon L.

    2010-01-01

    Patients with damage involving left ventrolateral prefrontal cortex (left VLPFC) often show syntactic deficits. They also show exaggerated interference effects during a variety of non-syntactic tasks, including picture naming and working memory. Conceivably, both deficits could arise from inadequate biasing of competitive interactions during…

  18. Reduced Prefrontal Cortex Hemodynamic Response in Adults with Methamphetamine Induced Psychosis: Relevance for Impulsivity

    PubMed Central

    Yamamuro, Kazuhiko; Kimoto, Sohei; Iida, Junzo; Kishimoto, Naoko; Nakanishi, Yoko; Tanaka, Shohei; Ota, Toyosaku; Makinodan, Manabu; Kishimoto, Toshifumi

    2016-01-01

    Patients with methamphetamine abuse/dependence often exhibit high levels of impulsivity, which may be associated with the structural abnormalities and functional hypoactivities observed in the frontal cortex of these subjects. Although near-infrared spectroscopy (NIRS) is a simple and non-invasive method for characterizing the clinical features of various psychiatric illnesses, few studies have used NIRS to directly investigate the association between prefrontal cortical activity and inhibitory control in patients with methamphetamine-induced psychosis (MAP). Using a 24-channel NIRS system, we compared hemodynamic responses during the Stroop color-word task in 14 patients with MAP and 21 healthy controls matched for age, sex and premorbid IQ. In addition, we used the Barrett Impulsivity Scale-11 (BIS-11) to assess impulsivity between subject groups. The MAP group exhibited significantly less activation in the anterior and frontopolar prefrontal cortex accompanied by lower Stroop color-word task performance, compared with controls. Moreover, BIS-11 scores were significantly higher in the MAP group, and were negatively correlated with the hemodynamic responses in prefrontal cortex. Our data suggest that reduced hemodynamic responses in the prefrontal cortex might reflect higher levels of impulsivity in patients with MAP, providing new insights into disrupted inhibitory control observed in MAP. PMID:27050450

  19. Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    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…

  20. Effect of Prefrontal Cortex Damage on Resolving Lexical Ambiguity in Text

    ERIC Educational Resources Information Center

    Frattali, Carol; Hanna, Rebecca; McGinty, Anita Shukla; Gerber, Lynn; Wesley, Robert; Grafman, Jordan; Coelho, Carl

    2007-01-01

    The function of suppression of context-inappropriate meanings during lexical ambiguity resolution was examined in 25 adults with prefrontal cortex damage (PFCD) localized to the left (N = 8), right (N = 6), or bilaterally (N = 11); and 21 matched Controls. Results revealed unexpected inverse patterns of suppression between PFCD and Control groups,…

  1. Prefrontal Cortex Is Critical for Contextual Processing: Evidence from Brain Lesions

    ERIC Educational Resources Information Center

    Fogelson, Noa; Shah, Mona; Scabini, Donatella; Knight, Robert T.

    2009-01-01

    We investigated the role of prefrontal cortex (PFC) in local contextual processing using a combined event-related potentials and lesion approach. Local context was defined as the occurrence of a short predictive series of visual stimuli occurring before delivery of a target event. Targets were preceded by either randomized sequences of standards…

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

    ERIC Educational Resources Information Center

    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).…

  3. Extended self: spontaneous activation of medial prefrontal cortex by objects that are 'mine'.

    PubMed

    Kim, Kyungmi; Johnson, Marcia K

    2014-07-01

    The concept of extended self refers to the idea that people incorporate self-relevant others or objects into one's sense of self. Initial neural support for the notion of extended self was provided by fMRI evidence that medial prefrontal cortex (MPFC) showed greater activation while people imagined objects belonging to them compared with someone else (Kim & Johnson, 2012). This study investigated whether self-associated objects (i.e. 'mine') subsequently engage MPFC spontaneously when a task does not require explicit self-referential judgments. During fMRI scanning, participants detected 'oddballs' (objects with a specific frame color) intermixed with objects participants had previously imagined belonging to them or to someone else and previously unseen non-oddball objects. There was greater activity in MPFC and posterior cingulate cortex for those 'self-owned' objects that participants were more successful at imagining owning compared with 'other-owned' objects. In addition, change in object preference following the ownership manipulation (a mere ownership effect) was predicted by activity in MPFC. Overall, these results provide neural evidence for the idea that personally relevant external stimuli may be incorporated into one's sense of self. PMID:23696692

  4. Differential Effects of Homotypic vs. Heterotypic Chronic Stress Regimens on Microglial Activation in the Prefrontal Cortex

    PubMed Central

    Kopp, Brittany L.; Wick, Dayna; Herman, James P.

    2013-01-01

    Stress pathology is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and aberrant glucocorticoid responses. Recent studies indicate increases in prefrontal cortical ionized calcium-binding adapter molecule 1 (Iba-1) staining following repeated restraint, reflecting increased microglial densities. Our experiments tested expression of Iba-1 staining in the prelimbic cortex (PL), infralimbic cortex (IL) and the hypothalamic paraventricular nucleus (PVN) following two-week exposure to repeated restraint (RR) and chronic variable stress (CVS), representing homotypic and heterotypic regimens, respectively. Unstressed animals served as controls. We specifically examined Iba-1 immunofluorescence in layers 2 and 3 versus layers 5 and 6 of the PL and IL, using both cell number and field staining density. Iba-1 field staining density was increased in both the PL and IL following RR in comparison to controls. This effect was not observed following CVS. Furthermore, PVN Iba-1 immunoreactivity was not affected by either stress regimen. Cell number did not vary within any brain areas or across stress exposures. Changes in microglial field density did not reflect changes in vascular density. Increases in PL and IL microglial density indicate selective microglial activation during RR, perhaps due to mild stress in the context of limited elevations in anti-inflammatory glucocorticoid actions. Supported by NIH grants [MH049698 and MH069860]. PMID:23707717

  5. Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: An fMRI approach

    PubMed Central

    2012-01-01

    Background The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test. Methods We used functional magnetic resonance imaging (fMRI) to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels) and compared it to its single task components (reading or vowel pick-out alone). Results Behavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's areas 45, 46) was present only in the KPT. Conclusions Our results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance. PMID:22640773

  6. NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

    ERIC Educational Resources Information Center

    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2013-01-01

    Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

  7. Is the self special in the dorsomedial prefrontal cortex? An fMRI study.

    PubMed

    Yaoi, Ken; Osaka, Naoyuki; Osaka, Mariko

    2009-01-01

    In recent years, several neuroimaging studies have suggested that the neural basis of the self-referential process1 is special, especially in the medial prefrontal cortex (MPFC). However, it remains controversial whether activity of the MPFC (and other related brain regions) appears only during the self-referential process. We investigated the neural correlates during the processing of references to the self, close other (friend), and distant other (prime minister) using fMRI. In comparison with baseline findings, referential processing to the three kinds of persons defined above showed common activation patterns in the dorsomedial prefrontal cortex (DMPFC), left middle temporal gyrus, left angular gyrus, posterior cingulate cortex and right cerebellum. Additionally, percent changes in BOLD signal in five regions of interest demonstrated the same findings. The result indicated that DMPFC was not special for the self-referential process, while there are common neural bases for evaluating the personalities of the self and others. PMID:19588282

  8. Visual space is compressed in prefrontal cortex before eye movements.

    PubMed

    Zirnsak, Marc; Steinmetz, Nicholas A; Noudoost, Behrad; Xu, Kitty Z; Moore, Tirin

    2014-03-27

    We experience the visual world through a series of saccadic eye movements, each one shifting our gaze to bring objects of interest to the fovea for further processing. Although such movements lead to frequent and substantial displacements of the retinal image, these displacements go unnoticed. It is widely assumed that a primary mechanism underlying this apparent stability is an anticipatory shifting of visual receptive fields (RFs) from their presaccadic to their postsaccadic locations before movement onset. Evidence of this predictive 'remapping' of RFs has been particularly apparent within brain structures involved in gaze control. However, critically absent among that evidence are detailed measurements of visual RFs before movement onset. Here we show that during saccade preparation, rather than remap, RFs of neurons in a prefrontal gaze control area massively converge towards the saccadic target. We mapped the visual RFs of prefrontal neurons during stable fixation and immediately before the onset of eye movements, using multi-electrode recordings in monkeys. Following movements from an initial fixation point to a target, RFs remained stationary in retinocentric space. However, in the period immediately before movement onset, RFs shifted by as much as 18 degrees of visual angle, and converged towards the target location. This convergence resulted in a threefold increase in the proportion of RFs responding to stimuli near the target region. In addition, like in human observers, the population of prefrontal neurons grossly mislocalized presaccadic stimuli as being closer to the target. Our results show that RF shifts do not predict the retinal displacements due to saccades, but instead reflect the overriding perception of target space during eye movements. PMID:24670771

  9. Dopaminergic dysregulation in prefrontal cortex of rhesus monkeys following cocaine self-administration.

    PubMed

    McIntosh, Scot; Howell, Leonard; Hemby, Scott E

    2013-01-01

    Chronic cocaine administration regulates the expression of several proteins related to dopaminergic signaling and synaptic function in the mesocorticolimbic pathway, including the prefrontal cortex. Functional abnormalities in the prefrontal cortex are hypothesized to be due in part to the expression of proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys self-administered cocaine (i.v.) under limited (n = 4) and extended access conditions (n = 6). The abundance of surrogate markers of dopamine signaling and plasticity in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) were examined: glycosylated and non-glycosylated forms of the dopamine transporter (efficiency of dopamine transport), tyrosine hydroxylase (TH; marker of dopamine synthesis) and phosphorylated TH at Serine 30 and 40 (markers of enzyme activity), extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK 2), and phosphorylated ERK1 and ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity), and markers of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in dopamine signaling and response to cocaine). Extended cocaine access increased non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in TH expression were observed between groups for any of the regions, extended access induced significant elevations in pTH(Ser31) in all regions. In addition, a slight but significant reduction in phosphorylated pTH(Ser40) was found in the DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC but not in DLPFC or ACC. Furthermore, extended cocaine self-administration elicited significant increases in spinophilin protein expression in all regions. Results from the study provide insight into the biochemical alterations occurring in primate prefrontal cortex

  10. Dopaminergic Dysregulation in Prefrontal Cortex of Rhesus Monkeys Following Cocaine Self-Administration

    PubMed Central

    McIntosh, Scot; Howell, Leonard; Hemby, Scott E.

    2013-01-01

    Chronic cocaine administration regulates the expression of several proteins related to dopaminergic signaling and synaptic function in the mesocorticolimbic pathway, including the prefrontal cortex. Functional abnormalities in the prefrontal cortex are hypothesized to be due in part to the expression of proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys self-administered cocaine (i.v.) under limited (n = 4) and extended access conditions (n = 6). The abundance of surrogate markers of dopamine signaling and plasticity in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) were examined: glycosylated and non-glycosylated forms of the dopamine transporter (efficiency of dopamine transport), tyrosine hydroxylase (TH; marker of dopamine synthesis) and phosphorylated TH at Serine 30 and 40 (markers of enzyme activity), extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK 2), and phosphorylated ERK1 and ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity), and markers of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in dopamine signaling and response to cocaine). Extended cocaine access increased non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in TH expression were observed between groups for any of the regions, extended access induced significant elevations in pTHSer31 in all regions. In addition, a slight but significant reduction in phosphorylated pTHSer40 was found in the DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC but not in DLPFC or ACC. Furthermore, extended cocaine self-administration elicited significant increases in spinophilin protein expression in all regions. Results from the study provide insight into the biochemical alterations occurring in primate prefrontal cortex. PMID

  11. Prefrontal Cortex Haemodynamics and Affective Responses during Exercise: A Multi-Channel Near Infrared Spectroscopy Study

    PubMed Central

    Tempest, Gavin D.; Eston, Roger G.; Parfitt, Gaynor

    2014-01-01

    The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes) of affective (pleasure-displeasure) responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy) and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ) in oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff) were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a) all regions of the left hemisphere and (b) lateral (dorsal and ventral) regions followed by the midline (ventral) region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise. PMID:24788166

  12. Prefrontal cortex haemodynamics and affective responses during exercise: a multi-channel near infrared spectroscopy study.

    PubMed

    Tempest, Gavin D; Eston, Roger G; Parfitt, Gaynor

    2014-01-01

    The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes) of affective (pleasure-displeasure) responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy) and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ) in oxygenation (O2Hb), deoxygenation (HHb), blood volume (tHb) and haemoglobin difference (HbDiff) were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a) all regions of the left hemisphere and (b) lateral (dorsal and ventral) regions followed by the midline (ventral) region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise. PMID:24788166

  13. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU.

    PubMed

    Diamond, A; Prevor, M B; Callender, G; Druin, D P

    1997-01-01

    To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed. PMID:9421921

  14. Perseverative Interference with Object-in-Place Scene Learning in Rhesus Monkeys with Bilateral Ablation of Ventrolateral Prefrontal Cortex

    ERIC Educational Resources Information Center

    Baxter, Mark G.; Browning, Philip G. F.; Mitchell, Anna S.

    2008-01-01

    Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with…

  15. Damage To Dorsolateral Prefrontal Cortex Affects Tradeoffs Between Honesty And Self-Interest

    PubMed Central

    Zhu, Lusha; Jenkins, Adrianna C.; Set, Eric; Scabini, Donatella; Knight, Robert T.; Chiu, Pearl H.; King-Casas, Brooks; Hsu, Ming

    2014-01-01

    Substantial correlational evidence exists suggesting a critical role for prefrontal regions in honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. Here we show using the lesion method that damage to the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions where honesty concerns were absent. These results point to a causal role for DLPFC in enabling honest behavior. PMID:25174003

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

    PubMed Central

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

    2015-01-01

    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. PMID:25450230

  17. Working memory coding of analog stimulus properties in the human prefrontal cortex.

    PubMed

    Spitzer, Bernhard; Gloel, Matthias; Schmidt, Timo T; Blankenburg, Felix

    2014-08-01

    Building on evidence for working memory (WM) coding of vibrotactile frequency information in monkey prefrontal cortex, recent electroencephalography studies found frequency processing in human WM to be reflected by quantitative modulations of prefrontal upper beta activity (20-30 Hz) as a function of the to-be-maintained stimulus attribute. This kind of stimulus-dependent activity has been observed across different sensory modalities, suggesting a generalized role of prefrontal beta during abstract WM processing of quantitative magnitude information. However, until now the available empirical evidence for such quantitative WM representation remains critically limited to the retention of periodic stimulus frequencies. In the present experiment, we used retrospective cueing to examine the quantitative WM processing of stationary (intensity) and temporal (duration) attributes of a previously presented tactile stimulus. We found parametric modulations of prefrontal beta activity during cued WM processing of each type of quantitative information, in a very similar manner as had before been observed only for periodic frequency information. In particular, delayed prefrontal beta modulations systematically reflected the magnitude of the retrospectively selected stimulus attribute and were functionally linked to successful behavioral task performance. Together, these findings converge on a generalized role of stimulus-dependent prefrontal beta-band oscillations during abstract scaling of analog quantity information in human WM. PMID:23547134

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

    PubMed

    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. PMID:25450230

  19. Multisynaptic projections from the ventrolateral prefrontal cortex to hand and mouth representations of the monkey primary motor cortex.

    PubMed

    Miyachi, Shigehiro; Hirata, Yoshihiro; Inoue, Ken-ichi; Lu, Xiaofeng; Nambu, Atsushi; Takada, Masahiko

    2013-07-01

    Different sectors of the prefrontal cortex have distinct neuronal connections with higher-order sensory areas and/or limbic structures and are related to diverse aspects of cognitive functions, such as visual working memory and reward-based decision-making. Recent studies have revealed that the prefrontal cortex (PF), especially the lateral PF, is also involved in motor control. Hence, different sectors of the PF may contribute to motor behaviors with distinct body parts. To test this hypothesis anatomically, we examined the patterns of multisynaptic projections from the PF to regions of the primary motor cortex (MI) that represent the arm, hand, and mouth, using retrograde transsynaptic transport of rabies virus. Four days after rabies injections into the hand or mouth region, particularly dense neuron labeling was observed in the ventrolateral PF, including the convexity part of ventral area 46. After the rabies injections into the mouth region, another dense cluster of labeled neurons was seen in the orbitofrontal cortex (area 13). By contrast, rabies labeling of PF neurons was rather sparse in the arm-injection cases. The present results suggest that the PF-MI multisynaptic projections may be organized such that the MI hand and mouth regions preferentially receive cognitive information for execution of elaborate motor actions. PMID:23664864

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

    PubMed

    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. PMID:22572769

  1. rTMS of the Left Dorsolateral Prefrontal Cortex Modulates Dopamine Release in the Ipsilateral Anterior Cingulate Cortex and Orbitofrontal Cortex

    PubMed Central

    Cho, Sang Soo; Strafella, Antonio P.

    2009-01-01

    Background Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson's disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC) (areas 9/46) stimulation on prefrontal dopamine (DA). Methodology/Principal Findings Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [11C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [11C]FLB 457 binding potential (BP) in the ipsilateral subgenual anterior cingulate cortex (ACC) (BA 25/12), pregenual ACC (BA 32) and medial orbitofrontal cortex (BA 11). There were no significant changes in [11C]FLB 457 BP following right DLPFC rTMS. Conclusions/Significance To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [11C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases. PMID:19696930

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

    PubMed

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

    2012-03-01

    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. PMID:22286175

  3. Network resets in medial prefrontal cortex mark the onset of behavioral uncertainty.

    PubMed

    Karlsson, Mattias P; Tervo, Dougal G R; Karpova, Alla Y

    2012-10-01

    Regions within the prefrontal cortex are thought to process beliefs about the world, but little is known about the circuit dynamics underlying the formation and modification of these beliefs. Using a task that permits dissociation between the activity encoding an animal's internal state and that encoding aspects of behavior, we found that transient increases in the volatility of activity in the rat medial prefrontal cortex accompany periods when an animal's belief is modified after an environmental change. Activity across the majority of sampled neurons underwent marked, abrupt, and coordinated changes when prior belief was abandoned in favor of exploration of alternative strategies. These dynamics reflect network switches to a state of instability, which diminishes over the period of exploration as new stable representations are formed. PMID:23042898

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Prefrontal cortex involvement in creative problem solving in middle adolescence and adulthood.

    PubMed

    Kleibeuker, Sietske W; Koolschijn, P Cédric M P; Jolles, Dietsje D; Schel, Margot A; De Dreu, Carsten K W; Crone, Eveline A

    2013-07-01

    Creative cognition, defined as the generation of new yet appropriate ideas and solutions, serves important adaptive purposes. Here, we tested whether and how middle adolescence, characterized by transformations toward life independency and individuality, is a more profitable phase than adulthood for creative cognition. Behavioral and neural differences for creative problem solving in adolescents (15-17 years) and adults (25-30 years) were measured while performing a matchstick problem task (MPT) in the scanner and the creative ability test (CAT), a visuo-spatial divergent thinking task, outside the scanner. Overall performances were comparable, although MPT performance indicated an advantage for adolescents in creative problem solving. In addition, adolescents showed more activation in lateral prefrontal cortex (ventral and dorsal) during creative problem solving compared to adults. These areas correlated with performances on the MPT and the CAT performance. We discuss that extended prefrontal cortex activation in adolescence is important for exploration and aids in creative cognition. PMID:23624336

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

    PubMed Central

    Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Denburg, Natalie L.; Tranel, Daniel

    2013-01-01

    The False Tagging Theory (FTT) is a neuroanatomical model of belief and doubt processes that proposes a single, unique function for the prefrontal cortex. Here, we review evidence pertaining to the FTT, the implications of the FTT regarding fractionation of the prefrontal cortex, and the potential benefits of the FTT for new neuroanatomical conceptualizations of executive functions. The FTT provides a parsimonious account that may help overcome theoretical problems with prefrontal cortex mediated executive control such as the homunculus critique. Control in the FTT is examined via the “heuristics and biases” psychological framework for human judgment. The evidence indicates that prefrontal cortex mediated doubting is at the core of executive functioning and may explain some biases of intuitive judgments. PMID:23745103

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

    PubMed

    Asp, Erik; Manzel, Kenneth; Koestner, Bryan; Denburg, Natalie L; Tranel, Daniel

    2013-01-01

    The False Tagging Theory (FTT) is a neuroanatomical model of belief and doubt processes that proposes a single, unique function for the prefrontal cortex. Here, we review evidence pertaining to the FTT, the implications of the FTT regarding fractionation of the prefrontal cortex, and the potential benefits of the FTT for new neuroanatomical conceptualizations of executive functions. The FTT provides a parsimonious account that may help overcome theoretical problems with prefrontal cortex mediated executive control such as the homunculus critique. Control in the FTT is examined via the "heuristics and biases" psychological framework for human judgment. The evidence indicates that prefrontal cortex mediated doubting is at the core of executive functioning and may explain some biases of intuitive judgments. PMID:23745103

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

    PubMed

    Jäncke, Lutz; Cheetham, Marcus; Baumgartner, Thomas

    2009-05-01

    In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences. PMID:19753097

  9. Implicitly perceived vocal attractiveness modulates prefrontal cortex activity.

    PubMed

    Bestelmeyer, Patricia E G; Latinus, Marianne; Bruckert, Laetitia; Rouger, Julien; Crabbe, Frances; Belin, Pascal

    2012-06-01

    Social interactions involve more than "just" language. As important is a more primitive nonlinguistic mode of communication acting in parallel with linguistic processes and driving our decisions to a much higher degree than is generally suspected. Amongst the "honest signals" that influence our behavior is perceived vocal attractiveness. Not only does vocal attractiveness reflect important biological characteristics of the speaker, it also influences our social perceptions according to the "what sounds beautiful is good" phenomenon. Despite the widespread influence of vocal attractiveness on social interactions revealed by behavioral studies, its neural underpinnings are yet unknown. We measured brain activity while participants listened to a series of vocal sounds ("ah") and performed an unrelated task. We found that voice-sensitive auditory and inferior frontal regions were strongly correlated with implicitly perceived vocal attractiveness. While the involvement of auditory areas reflected the processing of acoustic contributors to vocal attractiveness ("distance to mean" and spectrotemporal regularity), activity in inferior prefrontal regions (traditionally involved in speech processes) reflected the overall perceived attractiveness of the voices despite their lack of linguistic content. These results suggest the strong influence of hidden nonlinguistic aspects of communication signals on cerebral activity and provide an objective measure of this influence. PMID:21828348

  10. Delayed-alternation performance after selective lesions within the prefrontal cortex of the cat.

    PubMed

    Markowitsch, H J; Pritzel, M; Kessler, J; Guldin, W; Freeman, R B

    1980-02-01

    On the basis of new neuroanatomical findings on relationships between subregions of the mediodorsal thalamic nucleus and the prefrontal cortex of the cat, it was attempted to investigate the relative importance of prefrontal subfields with the aim of obtaining evidence in favor of a functional inequality of different prefrontal subfields. Four areas, named presylvian (PRS), proreal (PR), dorsomedial (DM), and orbito-insular (OI) sectors, were ablated successfully in 30 adult animals. Performance of a 10-sec delayed-alternation task was compared pre- and postoperatively. Furthermore, most of the cats had to learn an extension of this task postoperatively, using a 20-sec delay period, and lastly, these animals were subjected to an extinction test. Significant performance differences were obtained between cats of different groups in all three tasks. Lesions of subregion PR, and even more of subregion PRS, led to severe behavioral deterioration, whereas lesions of subregion OI were without effect, when compared with the behavior of a sham-operated control group. PRS-cats, furthermore, showed motor disturbances during the first postoperative week. The results obtained suggest that it is possible to subdivide the cat's prefrontal cortex functionally. In addition, it is hypothesized that behavioral changes in cats of groups PRS and PR are due to an inability to use kinesthetic information properly. PMID:7284081

  11. Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex

    PubMed Central

    Kostopoulos, Penelope; Petrides, Michael

    2016-01-01

    There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral prefrontal cortex plays a critical role in the top–down modulation of activity within posterior cortical areas for the selective retrieval of specific aspects of a memorized experience, a functional process often referred to as active controlled retrieval. In the present functional neuroimaging study, we explore the neural bases of active retrieval for auditory nonverbal information, about which almost nothing is known. Human participants were scanned with functional magnetic resonance imaging (fMRI) in a task in which they were presented with short melodies from different locations in a simulated virtual acoustic environment within the scanner and were then instructed to retrieve selectively either the particular melody presented or its location. There were significant activity increases specifically within the midventrolateral prefrontal region during the selective retrieval of nonverbal auditory information. During the selective retrieval of information from auditory memory, the right midventrolateral prefrontal region increased its interaction with the auditory temporal region and the inferior parietal lobule in the right hemisphere. These findings provide evidence that the midventrolateral prefrontal cortical region interacts with specific posterior cortical areas in the human cerebral cortex for the selective retrieval of object and location features of an auditory memory experience. PMID:26831102

  12. Selective memory retrieval of auditory what and auditory where involves the ventrolateral prefrontal cortex.

    PubMed

    Kostopoulos, Penelope; Petrides, Michael

    2016-02-16

    There is evidence from the visual, verbal, and tactile memory domains that the midventrolateral prefrontal cortex plays a critical role in the top-down modulation of activity within posterior cortical areas for the selective retrieval of specific aspects of a memorized experience, a functional process often referred to as active controlled retrieval. In the present functional neuroimaging study, we explore the neural bases of active retrieval for auditory nonverbal information, about which almost nothing is known. Human participants were scanned with functional magnetic resonance imaging (fMRI) in a task in which they were presented with short melodies from different locations in a simulated virtual acoustic environment within the scanner and were then instructed to retrieve selectively either the particular melody presented or its location. There were significant activity increases specifically within the midventrolateral prefrontal region during the selective retrieval of nonverbal auditory information. During the selective retrieval of information from auditory memory, the right midventrolateral prefrontal region increased its interaction with the auditory temporal region and the inferior parietal lobule in the right hemisphere. These findings provide evidence that the midventrolateral prefrontal cortical region interacts with specific posterior cortical areas in the human cerebral cortex for the selective retrieval of object and location features of an auditory memory experience. PMID:26831102

  13. Activation of AMPA Receptors Mediates the Antidepressant Action of Deep Brain Stimulation of the Infralimbic Prefrontal Cortex.

    PubMed

    Jiménez-Sánchez, Laura; Castañé, Anna; Pérez-Caballero, Laura; Grifoll-Escoda, Marc; López-Gil, Xavier; Campa, Leticia; Galofré, Mireia; Berrocoso, Esther; Adell, Albert

    2016-06-01

    Although deep brain stimulation (DBS) has been used with success in treatment-resistant depression, little is known about its mechanism of action. We examined the antidepressant-like activity of short (1 h) DBS applied to the infralimbic prefrontal cortex in the forced swim test (FST) and the novelty-suppressed feeding test (NSFT). We also used in vivo microdialysis to evaluate the release of glutamate, γ-aminobutyric acid, serotonin, dopamine, and noradrenaline in the prefrontal cortex and c-Fos immunohistochemistry to determine the brain regions activated by DBS. One hour of DBS of the infralimbic prefrontal cortex has antidepressant-like effects in FST and NSFT, and increases prefrontal efflux of glutamate, which would activate AMPA receptors (AMPARs). This effect is specific of the infralimbic area since it is not observed after DBS of the prelimbic subregion. The activation of prefrontal AMPARs would result in a stimulation of prefrontal output to the brainstem, thus increasing serotonin, dopamine, and noradrenaline in the prefrontal cortex. Further, the activation of prefrontal AMPARs is necessary and sufficient condition for the antidepressant response of 1 h DBS. PMID:26088969

  14. Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex

    PubMed Central

    Gläscher, Jan; Adolphs, Ralph; Damasio, Hanna; Bechara, Antoine; Rudrauf, David; Calamia, Matthew; Paul, Lynn K.; Tranel, Daniel

    2012-01-01

    A considerable body of previous research on the prefrontal cortex (PFC) has helped characterize the regional specificity of various cognitive functions, such as cognitive control and decision making. Here we provide definitive findings on this topic, using a neuropsychological approach that takes advantage of a unique dataset accrued over several decades. We applied voxel-based lesion-symptom mapping in 344 individuals with focal lesions (165 involving the PFC) who had been tested on a comprehensive battery of neuropsychological tasks. Two distinct functional-anatomical networks were revealed within the PFC: one associated with cognitive control (response inhibition, conflict monitoring, and switching), which included the dorsolateral prefrontal cortex and anterior cingulate cortex and a second associated with value-based decision-making, which included the orbitofrontal, ventromedial, and frontopolar cortex. Furthermore, cognitive control tasks shared a common performance factor related to set shifting that was linked to the rostral anterior cingulate cortex. By contrast, regions in the ventral PFC were required for decision-making. These findings provide detailed causal evidence for a remarkable functional-anatomical specificity in the human PFC. PMID:22908286

  15. Temperament Type Specific Metabolite Profiles of the Prefrontal Cortex and Serum in Cattle

    PubMed Central

    Brand, Bodo; Hadlich, Frieder; Brandt, Bettina; Schauer, Nicolas; Graunke, Katharina L.; Langbein, Jan; Repsilber, Dirk; Ponsuksili, Siriluk; Schwerin, Manfred

    2015-01-01

    In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response

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

    PubMed Central

    Hwang, Jaewon; Romanski, Lizabeth M.

    2015-01-01

    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. SIGNIFICANCE STATEMENT 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

  17. Longitudinal Changes in Prefrontal Cortex Activation Underlie Declines in Adolescent Risk Taking

    PubMed Central

    Galvan, Adriana; Fuligni, Andrew J.; Lieberman, Matthew D.

    2015-01-01

    Adolescence is a critical developmental phase during which risk-taking behaviors increase across a variety of species, raising the importance of understanding how brain changes contribute to such behaviors. While the prefrontal cortex is thought to influence adolescent risk taking, the specific ways in which it functions are unclear. Using longitudinal functional magnetic resonance imaging in human adolescents, we found that ventrolateral prefrontal cortex (VLPFC) activation decreased during an experimental risk-taking task over time, with greater declines in VLPFC associated with greater declines in self-reported risky behavior. Furthermore, greater decreases in functional coupling between the medial prefrontal cortex (MPFC) and ventral striatum over time were associated with decreases in self-reported risky behavior. Thus, disparate roles of the VLPFC and MPFC modulate longitudinal declines in adolescent risk taking. SIGNIFICANCE STATEMENT Adolescence is a developmental period marked by steep increases in risk-taking behavior coupled with dramatic brain changes. Although theories propose that the prefrontal cortex (PFC) may influence adolescent risk taking, the specific ways in which it functions remain unclear. We report the first longitudinal functional magnetic resonance imaging study to examine how neural activation during risk taking changes over time and contributes to adolescents' real-life risk-taking behavior. We find that longitudinal declines in activation of the ventrolateral PFC are linked to declines in adolescent risk taking, whereas the medial PFC influences adolescent risk taking via its functional neural coupling with reward-related regions. This is the first study to identify the mechanism by which different regions of the PFC disparately contribute to declines in risk taking. PMID:26269638

  18. Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample.

    PubMed

    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. PMID:26166620

  19. Task-Specific Facilitation of Cognition by Anodal Transcranial Direct Current Stimulation of the Prefrontal Cortex

    PubMed Central

    Pope, Paul A.; Brenton, Jonathan W.; Miall, R. Chris

    2015-01-01

    We previously speculated that depression of cerebellar excitability using cathodal transcranial direct current stimulation (tDCS) might release extra cognitive resources via the disinhibition of activity in prefrontal cortex. The objective of the present study was to investigate whether anodal tDCS over the prefrontal cortex could similarly improve performance when cognitive demands are high. Sixty-three right-handed participants in 3 separate groups performed the Paced Auditory Serial Addition Task (PASAT) and the more difficult Paced Auditory Serial Subtraction Task (PASST), before and after 20 min of anodal, cathodal, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC). Performance was assessed in terms of the accuracy, latency, and variability of correct verbal responses. All behavioral measures significantly improved for the PASST after anodal DLPFC stimulation, but not the PASAT. There were smaller practice effects after cathodal and sham stimulation. Subjective ratings of attention and mental fatigue were unchanged by tDCS over time. We conclude that anodal stimulation over the left DLPFC can selectively improve performance on a difficult cognitive task involving arithmetic processing, verbal working memory, and attention. This result might be achieved by focally improving executive functions and/or cognitive capacity when tasks are difficult, rather than by improving levels of arousal/alertness. PMID:25979089

  20. Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

    PubMed Central

    Zikopoulos, Basilis; Barbas, Helen

    2007-01-01

    Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases. PMID:17786219

  1. Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats.

    PubMed

    Sirohi, Sunil; Walker, Brendan M

    2015-11-01

    Opioid receptors can display spontaneous agonist-independent G-protein signaling (basal signaling/constitutive activity). While constitutive κ-opioid receptor (KOR) activity has been documented in vitro, it remains unknown if KORs are constitutively active in native systems. Using [(35) S] guanosine 5'-O-[gamma-thio] triphosphate coupling assay that measures receptor functional state, we identified the presence of medial prefrontal cortex KOR constitutive activity in young rats that declined with age. Furthermore, basal signaling showed an age-related decline and was insensitive to neutral opioid antagonist challenge. Collectively, the present data are first to demonstrate age-dependent alterations in the medial prefrontal cortex KOR constitutive activity in rats and changes in the constitutive activity of KORs can differentially impact KOR ligand efficacy. These data provide novel insights into the functional properties of the KOR system and warrant further consideration of KOR constitutive activity in normal and pathophysiological behavior. Opioid receptors exhibit agonist-independent constitutive activity; however, kappa-opioid receptor (KOR) constitutive activity has not been demonstrated in native systems. Our results confirm KOR constitutive activity in the medial prefrontal cortex (mPFC) that declines with age. With the ability to presynaptically inhibit multiple neurotransmitter systems in the mPFC, maturational or patho-logical alterations in constitutive activity could disrupt corticofugal glutamatergic pyramidal projection neurons mediating executive function. Regulation of KOR constitutive activity could serve as a therapeutic target to treat compromised executive function. PMID:26257334

  2. The Role of the Medial Prefrontal Cortex in the Conditioning and Extinction of Fear

    PubMed Central

    Giustino, Thomas F.; Maren, Stephen

    2015-01-01

    Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD). As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) regulate the expression and suppression of fear in rodents, respectively. Here, we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression. PMID:26617500

  3. Task-Specific Facilitation of Cognition by Anodal Transcranial Direct Current Stimulation of the Prefrontal Cortex.

    PubMed

    Pope, Paul A; Brenton, Jonathan W; Miall, R Chris

    2015-11-01

    We previously speculated that depression of cerebellar excitability using cathodal transcranial direct current stimulation (tDCS) might release extra cognitive resources via the disinhibition of activity in prefrontal cortex. The objective of the present study was to investigate whether anodal tDCS over the prefrontal cortex could similarly improve performance when cognitive demands are high. Sixty-three right-handed participants in 3 separate groups performed the Paced Auditory Serial Addition Task (PASAT) and the more difficult Paced Auditory Serial Subtraction Task (PASST), before and after 20 min of anodal, cathodal, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC). Performance was assessed in terms of the accuracy, latency, and variability of correct verbal responses. All behavioral measures significantly improved for the PASST after anodal DLPFC stimulation, but not the PASAT. There were smaller practice effects after cathodal and sham stimulation. Subjective ratings of attention and mental fatigue were unchanged by tDCS over time. We conclude that anodal stimulation over the left DLPFC can selectively improve performance on a difficult cognitive task involving arithmetic processing, verbal working memory, and attention. This result might be achieved by focally improving executive functions and/or cognitive capacity when tasks are difficult, rather than by improving levels of arousal/alertness. PMID:25979089

  4. On Parsing the Neural Code in the Prefrontal Cortex of Primates using Principal Dynamic Modes

    PubMed Central

    Marmarelis, V. Z.; Shin, D. C.; Song, D.; Hampson, R. E.; Deadwyler, S. A.; Berger, T. W.

    2013-01-01

    Nonlinear modeling of multi-input multi-output (MIMO) neuronal systems using Principal Dynamic Modes (PDMs) provides a novel method for analyzing the functional connectivity between neuronal groups. This paper presents the PDM-based modeling methodology and initial results from actual multi-unit recordings in the prefrontal cortex of non-human primates. We used the PDMs to analyze the dynamic transformations of spike train activity from Layer 2 (input) to Layer 5 (output) of the prefrontal cortex in primates performing a Delayed-Match-to-Sample task. The PDM-based models reduce the complexity of representing large-scale neural MIMO systems that involve large numbers of neurons, and also offer the prospect of improved biological/physiological interpretation of the obtained models. PDM analysis of neuronal connectivity in this system revealed "input-output channels of communication" corresponding to specific bands of neural rhythms that quantify the relative importance of these frequency-specific PDMs across a variety of different tasks. We found that behavioral performance during the Delayed-Match-to-Sample task (correct vs. incorrect outcome) was associated with differential activation of frequency-specific PDMs in the prefrontal cortex. PMID:23929124

  5. Evidence for Mediodorsal Thalamus and Prefrontal Cortex Interactions during Cognition in Macaques

    PubMed Central

    Browning, Philip G. F.; Chakraborty, Subhojit; Mitchell, Anna S.

    2015-01-01

    It is proposed that mediodorsal thalamus contributes to cognition via interactions with prefrontal cortex. However, there is relatively little evidence detailing the interactions between mediodorsal thalamus and prefrontal cortex linked to cognition in primates. This study investigated these interactions during learning, memory, and decision-making tasks in rhesus monkeys using a disconnection lesion approach. Preoperatively, monkeys learned object-in-place scene discriminations embedded within colorful visual backgrounds. Unilateral neurotoxic lesions to magnocellular mediodorsal thalamus (MDmc) impaired the ability to learn new object-in-place scene discriminations. In contrast, unilateral ablations to ventrolateral and orbital prefrontal cortex (PFv+o) left learning intact. A second unilateral MDmc or PFv+o lesion in the contralateral hemisphere to the first operation, causing functional MDmc–PFv+o disconnection across hemispheres, further impaired learning object-in-place scene discriminations, although object discrimination learning remained intact. Adaptive decision-making after reward satiety devaluation was also reduced. These data highlight the functional importance of interactions between MDmc and PFv+o during learning object-in-place scene discriminations and adaptive decision-making but not object discrimination learning. Moreover, learning deficits observed after unilateral removal of MDmc but not PFv+o provide direct behavioral evidence of the MDmc role influencing more widespread regions of the frontal lobes in cognition. PMID:25979086

  6. Evidence for Mediodorsal Thalamus and Prefrontal Cortex Interactions during Cognition in Macaques.

    PubMed

    Browning, Philip G F; Chakraborty, Subhojit; Mitchell, Anna S

    2015-11-01

    It is proposed that mediodorsal thalamus contributes to cognition via interactions with prefrontal cortex. However, there is relatively little evidence detailing the interactions between mediodorsal thalamus and prefrontal cortex linked to cognition in primates. This study investigated these interactions during learning, memory, and decision-making tasks in rhesus monkeys using a disconnection lesion approach. Preoperatively, monkeys learned object-in-place scene discriminations embedded within colorful visual backgrounds. Unilateral neurotoxic lesions to magnocellular mediodorsal thalamus (MDmc) impaired the ability to learn new object-in-place scene discriminations. In contrast, unilateral ablations to ventrolateral and orbital prefrontal cortex (PFv+o) left learning intact. A second unilateral MDmc or PFv+o lesion in the contralateral hemisphere to the first operation, causing functional MDmc-PFv+o disconnection across hemispheres, further impaired learning object-in-place scene discriminations, although object discrimination learning remained intact. Adaptive decision-making after reward satiety devaluation was also reduced. These data highlight the functional importance of interactions between MDmc and PFv+o during learning object-in-place scene discriminations and adaptive decision-making but not object discrimination learning. Moreover, learning deficits observed after unilateral removal of MDmc but not PFv+o provide direct behavioral evidence of the MDmc role influencing more widespread regions of the frontal lobes in cognition. PMID:25979086

  7. The Role of the Medial Prefrontal Cortex in the Conditioning and Extinction of Fear.

    PubMed

    Giustino, Thomas F; Maren, Stephen

    2015-01-01

    Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD). As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) regulate the expression and suppression of fear in rodents, respectively. Here, we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression. PMID:26617500

  8. Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats

    PubMed Central

    Liu, Albert; Jain, Neeraj; Vyas, Ajai; Lim, Lee Wei

    2015-01-01

    Memory dysfunction is a key symptom of age-related dementia. Although recent studies have suggested positive effects of electrical stimulation for memory enhancement, its potential targets remain largely unknown. In this study, we hypothesized that spatially targeted deep brain stimulation of ventromedial prefrontal cortex enhanced memory functions in a middle-aged rat model. Our results show that acute stimulation enhanced the short-, but not the long-term memory in the novel-object recognition task. Interestingly, after chronic high-frequency stimulation, both the short- and long-term memories were robustly improved in the novel-object recognition test and Morris water-maze spatial task compared to sham. Our results also demonstrated that chronic ventromedial prefrontal cortex high-frequency stimulation upregulated neurogenesis-associated genes along with enhanced hippocampal cell proliferation. Importantly, these memory behaviors were strongly correlated with the hippocampal neurogenesis. Overall, these findings suggest that chronic ventromedial prefrontal cortex high-frequency stimulation may serve as a novel effective therapeutic target for dementia-related disorders. DOI: http://dx.doi.org/10.7554/eLife.04803.001 PMID:25768425

  9. Claustrum projections to prefrontal cortex in the capuchin monkey (Cebus apella)

    PubMed Central

    Reser, David H.; Richardson, Karyn E.; Montibeller, Marina O.; Zhao, Sherry; Chan, Jonathan M. H.; Soares, Juliana G. M.; Chaplin, Tristan A.; Gattass, Ricardo; Rosa, Marcello G. P.

    2014-01-01

    We examined the pattern of retrograde tracer distribution in the claustrum following intracortical injections into the frontal pole (area 10), and in dorsal (area 9), and ventral lateral (area 12) regions of the rostral prefrontal cortex in the tufted capuchin monkey (Cebus apella). The resulting pattern of labeled cells was assessed in relation to the three-dimensional geometry of the claustrum, as well as recent reports of claustrum-prefrontal connections in other primates. Claustrum-prefrontal projections were extensive, and largely concentrated in the ventral half of the claustrum, especially in the rostral 2/3 of the nucleus. Our data are consistent with a topographic arrangement of claustrum-cortical connections in which prefrontal and association cortices receive connections largely from the rostral and medial claustrum. Comparative aspects of claustrum-prefrontal topography across primate species and the implications of claustrum connectivity for understanding of cortical functional networks are explored, and we hypothesize that the claustrum may play a role in controlling or switching between resting state and task-associated cortical networks. PMID:25071475

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

    PubMed

    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. PMID:26790349