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Sample records for prefrontal cortex neuronal

  1. Glucose-monitoring neurons in the mediodorsal prefrontal cortex.

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

    2012-03-20

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

  2. Encoding of Spatial Attention by Primate Prefrontal Cortex Neuronal Ensembles

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    Treue, Stefan

    2018-01-01

    Abstract Single neurons in the primate lateral prefrontal cortex (LPFC) encode information about the allocation of visual attention and the features of visual stimuli. However, how this compares to the performance of neuronal ensembles at encoding the same information is poorly understood. Here, we recorded the responses of neuronal ensembles in the LPFC of two macaque monkeys while they performed a task that required attending to one of two moving random dot patterns positioned in different hemifields and ignoring the other pattern. We found single units selective for the location of the attended stimulus as well as for its motion direction. To determine the coding of both variables in the population of recorded units, we used a linear classifier and progressively built neuronal ensembles by iteratively adding units according to their individual performance (best single units), or by iteratively adding units based on their contribution to the ensemble performance (best ensemble). For both methods, ensembles of relatively small sizes (n decoding performance relative to individual single units. However, the decoder reached similar performance using fewer neurons with the best ensemble building method compared with the best single units method. Our results indicate that neuronal ensembles within the LPFC encode more information about the attended spatial and nonspatial features of visual stimuli than individual neurons. They further suggest that efficient coding of attention can be achieved by relatively small neuronal ensembles characterized by a certain relationship between signal and noise correlation structures. PMID:29568798

  3. Single neurons in prefrontal cortex encode abstract rules.

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    Wallis, J D; Anderson, K C; Miller, E K

    2001-06-21

    The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on the prefrontal cortex (PFC) because its damage often results in difficulty in following rules. Here we explore its neural basis by recording from single neurons in the PFC of monkeys trained to use two abstract rules. They were required to indicate whether two successively presented pictures were the same or different depending on which rule was currently in effect. The monkeys performed this task with new pictures, thus showing that they had learned two general principles that could be applied to stimuli that they had not yet experienced. The most prevalent neuronal activity observed in the PFC reflected the coding of these abstract rules.

  4. Coding of vocalizations by single neurons in ventrolateral prefrontal cortex.

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    Plakke, Bethany; Diltz, Mark D; Romanski, Lizabeth M

    2013-11-01

    Neuronal activity in single prefrontal neurons has been correlated with behavioral responses, rules, task variables and stimulus features. In the non-human primate, neurons recorded in ventrolateral prefrontal cortex (VLPFC) have been found to respond to species-specific vocalizations. Previous studies have found multisensory neurons which respond to simultaneously presented faces and vocalizations in this region. Behavioral data suggests that face and vocal information are inextricably linked in animals and humans and therefore may also be tightly linked in the coding of communication calls in prefrontal neurons. In this study we therefore examined the role of VLPFC in encoding vocalization call type information. Specifically, we examined previously recorded single unit responses from the VLPFC in awake, behaving rhesus macaques in response to 3 types of species-specific vocalizations made by 3 individual callers. Analysis of responses by vocalization call type and caller identity showed that ∼19% of cells had a main effect of call type with fewer cells encoding caller. Classification performance of VLPFC neurons was ∼42% averaged across the population. When assessed at discrete time bins, classification performance reached 70 percent for coos in the first 300 ms and remained above chance for the duration of the response period, though performance was lower for other call types. In light of the sub-optimal classification performance of the majority of VLPFC neurons when only vocal information is present, and the recent evidence that most VLPFC neurons are multisensory, the potential enhancement of classification with the addition of accompanying face information is discussed and additional studies recommended. Behavioral and neuronal evidence has shown a considerable benefit in recognition and memory performance when faces and voices are presented simultaneously. In the natural environment both facial and vocalization information is present simultaneously and

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

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    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

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

  6. Motivation and Affective Judgments Differentially Recruit Neurons in the Primate Dorsolateral Prefrontal and Anterior Cingulate Cortex

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    Amemori, Ken-ichi; Amemori, Satoko

    2015-01-01

    The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach–avoidance (Ap–Av) and approach–approach (Ap–Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap–Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing. PMID:25653353

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

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    Romanski, L M; Diehl, M M

    2011-08-25

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

  8. Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

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    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

    2018-02-01

    Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Strategic neuronal encoding in medial prefrontal cortex of spatial working memory in the T-maze.

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    Yang, Yang; Mailman, Richard B

    2018-05-02

    Strategic neuronal encoding in the medial prefrontal cortex (mPFC) of the rat was correlated with spatial working memory (sWM) assessed by behavior in the T-maze. Neurons increased their firing rate around choice, with the increase largely occurring before choice as a prospective encode of behavior. This could be classified as sensitive-to-spatial information or sensitive-to-choice outcome. The sensitivity-to-spatial choice was defined by distinct firing rate changes before left- or right-choice. The percentage of left-choice sensitive neurons was not different from the percentage of right-choice sensitive neurons. There was also location-related neuronal activity in which neurons fired at distinct rates when rats were in a left- or right-location. More neurons were sensitive to left-location, as most of them were recorded from rats preferring to enter the right-location. The sensitivity to outcome was defined by a distinct firing rate around correct or error choice. Significantly more neurons were sensitive to error outcome, and, among these, more preferred to encode prospectively, increasing firing in advance of an error outcome. Similar to single neuron activity, the mPFC enhanced its neuronal network as measured by the oscillation of local field potential. The maximum power of oscillation was around choice, and occurred slightly earlier before error versus before correct outcome. Thus, sWM modulation in the mPFC includes not only spatial, but also outcome-related inputs, and neuronal ensembles monitor behavioral outcome to make strategic adjustments ensuring successful task performance. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. From rule to response: neuronal processes in the premotor and prefrontal cortex.

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    Wallis, Jonathan D; Miller, Earl K

    2003-09-01

    The ability to use abstract rules or principles allows behavior to generalize from specific circumstances (e.g., rules learned in a specific restaurant can subsequently be applied to any dining experience). Neurons in the prefrontal cortex (PFC) encode such rules. However, to guide behavior, rules must be linked to motor responses. We investigated the neuronal mechanisms underlying this process by recording from the PFC and the premotor cortex (PMC) of monkeys trained to use two abstract rules: "same" or "different." The monkeys had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The abstract rules were represented in both regions, although they were more prevalent and were encoded earlier and more strongly in the PMC. There was a perceptual bias in the PFC, relative to the PMC, with more PFC neurons encoding the presented pictures. In contrast, neurons encoding the behavioral response were more prevalent in the PMC, and the selectivity was stronger and appeared earlier in the PMC than in the PFC.

  11. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

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

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

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

    2017-01-01

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

  13. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond.

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    Hrvoj-Mihic, Branka; Hanson, Kari L; Lew, Caroline H; Stefanacci, Lisa; Jacobs, Bob; Bellugi, Ursula; Semendeferi, Katerina

    2017-01-01

    Williams syndrome (WS) is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC)-the frontal pole (Brodmann area 10) and the orbitofrontal cortex (Brodmann area 11)-and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18). The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10) and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other neurodevelopmental disorders

  14. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond

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    Branka Hrvoj-Mihic

    2017-08-01

    Full Text Available Williams syndrome (WS is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC—the frontal pole (Brodmann area 10 and the orbitofrontal cortex (Brodmann area 11—and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18. The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10 and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other

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

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    Gabbott, Paul L; Rolls, Edmund T

    2013-06-01

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

  16. Prenatal NMDA Receptor Antagonism Impaired Proliferation of Neuronal Progenitor, Leading to Fewer Glutamatergic Neurons in the Prefrontal Cortex

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    Toriumi, Kazuya; Mouri, Akihiro; Narusawa, Shiho; Aoyama, Yuki; Ikawa, Natsumi; Lu, Lingling; Nagai, Taku; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

    2012-01-01

    N-methyl--aspartate (NMDA) receptor is a glutamate receptor which has an important role on mammalian brain development. We have reported that prenatal treatment with phencyclidine (PCP), a NMDA receptor antagonist, induces long-lasting behavioral deficits and neurochemical changes. However, the mechanism by which the prenatal antagonism of NMDA receptor affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that prenatal NMDA receptor antagonism impaired the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and the subventricular zone. Furthermore, using a PCR array focused on neurogenesis and neuronal stem cells, we evaluated changes in gene expression causing the impairment of neuronal progenitor proliferation and found aberrant gene expression, such as Notch2 and Ntn1, in prenatal PCP-treated mice. Consequently, the density of glutamatergic neurons in the prefrontal cortex was decreased, probably resulting in glutamatergic hypofunction. Prenatal PCP-treated mice displayed behavioral deficits in cognitive memory and sensorimotor gating until adulthood. These findings suggest that NMDA receptors regulate the proliferation and maturation of progenitor cells for glutamatergic neuron during neurodevelopment, probably via the regulation of gene expression. PMID:22257896

  17. Transcriptional dysregulation of γ-aminobutyric acid transporter in parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia.

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    Bitanihirwe, Byron K Y; Woo, Tsung-Ung W

    2014-12-30

    Parvalbumin (PV)-containing neurons are functionally compromised in schizophrenia. Using double in situ hybridization in postmortem human prefrontal cortex, we found that the messenger RNA (mRNA) for the γ-aminobutyric acid (GABA) transporter GAT-1 was undetectable in 22-41% of PV neurons in layers 3-4 in schizophrenia. In the remaining PV neurons with detectable GAT-1 mRNA, transcript expression was decreased by 26% in layer 3. Hence, the dysfunction of PV neurons involves the molecular dysregulation of presynaptic GABA reuptake. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

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    Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

    2018-03-01

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

  19. Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

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    Aoyama, Yuki; Toriumi, Kazuya; Mouri, Akihiro; Hattori, Tomoya; Ueda, Eriko; Shimato, Akane; Sakakibara, Nami; Soh, Yuka; Mamiya, Takayoshi; Nagai, Taku; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Nabeshima, Toshitaka; Yamada, Kiyofumi

    2016-01-01

    Cigarette smoking during pregnancy is associated with various disabilities in the offspring such as attention deficit/hyperactivity disorder, learning disabilities, and persistent anxiety. We have reported that nicotine exposure in female mice during pregnancy, in particular from embryonic day 14 (E14) to postnatal day 0 (P0), induces long-lasting behavioral deficits in offspring. However, the mechanism by which prenatal nicotine exposure (PNE) affects neurodevelopment, resulting in behavioral deficits, has remained unclear. Here, we report that PNE disrupted the proliferation of neuronal progenitors, leading to a decrease in the progenitor pool in the ventricular and subventricular zones. In addition, using a cumulative 5-bromo-2′-deoxyuridine labeling assay, we evaluated the rate of cell cycle progression causing the impairment of neuronal progenitor proliferation, and uncovered anomalous cell cycle kinetics in mice with PNE. Accordingly, the density of glutamatergic neurons in the medial prefrontal cortex (medial PFC) was reduced, implying glutamatergic dysregulation. Mice with PNE exhibited behavioral impairments in attentional function and behavioral flexibility in adulthood, and the deficits were ameliorated by microinjection of D-cycloserine into the PFC. Collectively, our findings suggest that PNE affects the proliferation and maturation of progenitor cells to glutamatergic neuron during neurodevelopment in the medial PFC, which may be associated with cognitive deficits in the offspring. PMID:26105135

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

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

    2014-01-16

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

  1. Mechanisms Underlying Serotonergic Excitation of Callosal Projection Neurons in the Mouse Medial Prefrontal Cortex

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    Emily K. Stephens

    2018-01-01

    Full Text Available Serotonin (5-HT selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current, or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs. However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation in commissural/callosal (COM projection neurons, a subpopulation of pyramidal neurons that exhibits 2A-dependent excitation in response to 5-HT. In baseline conditions, 5-HT enhanced the rate of action potential generation in COM neurons experiencing suprathreshold somatic current injection. This serotonergic excitation was occluded by activation of muscarinic acetylcholine (ACh receptors, confirming that 5-HT acts via the same Gq-signaling cascades engaged by ACh. Like ACh, 5-HT promoted the generation of calcium-dependent ADPs following spike trains. However, calcium was not necessary for serotonergic excitation, as responses to 5-HT were enhanced (by >100%, rather than reduced, by chelation of intracellular calcium with 10 mM BAPTA. This suggests intracellular calcium negatively regulates additional ionic conductances gated by 2A receptors. Removal of extracellular calcium had no effect when intracellular calcium signaling was intact, but suppressed 5-HT response amplitudes, by about 50%, when BAPTA was included in patch pipettes. This suggests that 2A excitation involves activation of a non-specific cation conductance that is both calcium-sensitive and calcium-permeable. M-current suppression was found to be a third

  2. Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

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    Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

    2011-01-01

    Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID

  3. Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Samantha J Fung

    Full Text Available Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC. Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX, a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque and density of white matter neurons (humans during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37 and matched controls (n = 37 and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in

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

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    Roelf J. Cruz-Rizzolo

    2017-12-01

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

  5. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  7. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

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    Andrea Forero

    2017-09-01

    Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

  8. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

    Science.gov (United States)

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

    2016-02-01

    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

  9. Auditory Connections and Functions of Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Bethany ePlakke

    2014-07-01

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

  10. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

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

  11. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure.

    Science.gov (United States)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo; Rydbirk, Rasmus; Olesen, Mikkel Vestergaard; Hay-Schmidt, Anders; Pakkenberg, Bente; Aznar, Susana

    2017-05-30

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT 2A receptor (5-HT 2A R) dependent. Here, we further investigated how blockade of 5-HT 2A Rs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT 2A R blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT 2A R activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT 2A R blockade does not seem to affect the amygdala-striatal projection. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Acquisition, extinction, and recall of opiate reward memory are signaled by dynamic neuronal activity patterns in the prefrontal cortex.

    Science.gov (United States)

    Sun, Ninglei; Chi, Ning; Lauzon, Nicole; Bishop, Stephanie; Tan, Huibing; Laviolette, Steven R

    2011-12-01

    The medial prefrontal cortex (mPFC) comprises an important component in the neural circuitry underlying drug-related associative learning and memory processing. Neuronal activation within mPFC circuits is correlated with the recall of opiate-related drug-taking experiences in both humans and other animals. Using an unbiased associative place conditioning procedure, we recorded mPFC neuronal populations during the acquisition, recall, and extinction phases of morphine-related associative learning and memory. Our analyses revealed that mPFC neurons show increased activity both in terms of tonic and phasic activity patterns during the acquisition phase of opiate reward-related memory and demonstrate stimulus-locked associative activity changes in real time, during the recall of opiate reward memories. Interestingly, mPFC neuronal populations demonstrated divergent patterns of bursting activity during the acquisition versus recall phases of newly acquired opiate reward memory, versus the extinction of these memories, with strongly increased bursting during the recall of an extinction memory and no associative bursting during the recall of a newly acquired opiate reward memory. Our results demonstrate that neurons within the mPFC are involved in both the acquisition, recall, and extinction of opiate-related reward memories, showing unique patterns of tonic and phasic activity patterns during these separate components of the opiate-related reward learning and memory recall.

  13. Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

    KAUST Repository

    Virtanen, Mari A.; Lacoh, Claudia Marvine; Fiumelli, Hubert; Kosel, Markus; Tyagarajan, Shiva; de Roo, Mathias; Vutskits, Laszlo

    2018-01-01

    Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.

  14. Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the rat medial prefrontal cortex

    KAUST Repository

    Virtanen, Mari A.

    2018-01-10

    Inhibitory control of pyramidal neurons plays a major role in governing the excitability in the brain. While spatial mapping of inhibitory inputs onto pyramidal neurons would provide important structural data on neuronal signaling, studying their distribution at the single cell level is difficult due to the lack of easily identifiable anatomical proxies. Here, we describe an approach where in utero electroporation of a plasmid encoding for fluorescently tagged gephyrin into the precursors of pyramidal cells along with ionotophoretic injection of Lucifer Yellow can reliably and specifically detect GABAergic synapses on the dendritic arbour of single pyramidal neurons. Using this technique and focusing on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto these cells between postnatal days 10 and 20. While the spatial distribution of gephyrin clusters was not affected by the distance from the cell body at postnatal day 10, we found that distal dendritic segments appeared to have a higher gephyrin density at later developmental stages. We also show a transient increase around postnatal day 20 in the percentage of spines that are carrying a gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the precise spatial arrangement of synaptic inputs is an important determinant of neuronal responses, we believe that the method described in this work may allow a better understanding of how inhibition settles together with excitation, and serve as basics for further modelling studies focusing on the geometry of dendritic inhibition during development.

  15. Shift in the intrinsic excitability of medial prefrontal cortex neurons following training in impulse control and cued-responding tasks.

    Directory of Open Access Journals (Sweden)

    Scott J Hayton

    Full Text Available Impulse control is an executive process that allows animals to inhibit their actions until an appropriate time. Previously, we reported that learning a simple response inhibition task increases AMPA currents at excitatory synapses in the prelimbic region of the medial prefrontal cortex (mPFC. Here, we examined whether modifications to intrinsic excitability occurred alongside the synaptic changes. To that end, we trained rats to obtain a food reward in a response inhibition task by withhold responding on a lever until they were signaled to respond. We then measured excitability, using whole-cell patch clamp recordings in brain slices, by quantifying action potentials generated by the injection of depolarizing current steps. Training in this task depressed the excitability of layer V pyramidal neurons of the prelimbic, but not infralimbic, region of the mPFC relative to behavioral controls. This decrease in maximum spiking frequency was significantly correlated with performance on the final session of the task. This change in intrinsic excitability may represent a homeostatic mechanism counterbalancing increased excitatory synaptic inputs onto those neurons in trained rats. Interestingly, subjects trained with a cue that predicted imminent reward availability had increased excitability in infralimbic, but not the prelimbic, pyramidal neurons. This dissociation suggests that both prelimbic and infralimbic neurons are involved in directing action, but specialized for different types of information, inhibitory or anticipatory, respectively.

  16. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

    DEFF Research Database (Denmark)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo

    2017-01-01

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field...... of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5 mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time...... spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin...

  17. Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

    Science.gov (United States)

    Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

    2017-06-15

    TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Working Memory in the Prefrontal Cortex

    Science.gov (United States)

    Funahashi, Shintaro

    2017-01-01

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

  19. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    Science.gov (United States)

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  20. Selective expression of KCNS3 potassium channel α-subunit in parvalbumin-containing GABA neurons in the human prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Danko Georgiev

    Full Text Available The cognitive deficits of schizophrenia appear to be associated with altered cortical GABA neurotransmission in the subsets of inhibitory neurons that express either parvalbumin (PV or somatostatin (SST. Identification of molecular mechanisms that operate selectively in these neurons is essential for developing targeted therapeutic strategies that do not influence other cell types. Consequently, we sought to identify, in the human cortex, gene products that are expressed selectively by PV and/or SST neurons, and that might contribute to their distinctive functional properties. Based on previously reported expression patterns in the cortex of mice and humans, we selected four genes: KCNS3, LHX6, KCNAB1, and PPP1R2, encoding K(+ channel Kv9.3 modulatory α-subunit, LIM homeobox protein 6, K(+ channel Kvβ1 subunit, and protein phosphatase 1 regulatory subunit 2, respectively, and examined their colocalization with PV or SST mRNAs in the human prefrontal cortex using dual-label in situ hybridization with (35S- and digoxigenin-labeled antisense riboprobes. KCNS3 mRNA was detected in almost all PV neurons, but not in SST neurons, and PV mRNA was detected in >90% of KCNS3 mRNA-expressing neurons. LHX6 mRNA was detected in almost all PV and >90% of SST neurons, while among all LHX6 mRNA-expressing neurons 50% expressed PV mRNA and >44% expressed SST mRNA. KCNAB1 and PPP1R2 mRNAs were detected in much larger populations of cortical neurons than PV or SST neurons. These findings indicate that KCNS3 is a selective marker of PV neurons, whereas LHX6 is expressed by both PV and SST neurons. KCNS3 and LHX6 might be useful for characterizing cell-type specific molecular alterations of cortical GABA neurotransmission and for the development of novel treatments targeting PV and/or SST neurons in schizophrenia.

  1. Neuronal activity in primate prefrontal cortex related to goal-directed behavior during auditory working memory tasks.

    Science.gov (United States)

    Huang, Ying; Brosch, Michael

    2016-06-01

    Prefrontal cortex (PFC) has been documented to play critical roles in goal-directed behaviors, like representing goal-relevant events and working memory (WM). However, neurophysiological evidence for such roles of PFC has been obtained mainly with visual tasks but rarely with auditory tasks. In the present study, we tested roles of PFC in auditory goal-directed behaviors by recording local field potentials in the auditory region of left ventrolateral PFC while a monkey performed auditory WM tasks. The tasks consisted of multiple events and required the monkey to change its mental states to achieve the reward. The events were auditory and visual stimuli, as well as specific actions. Mental states were engaging in the tasks and holding task-relevant information in auditory WM. We found that, although based on recordings from one hemisphere in one monkey only, PFC represented multiple events that were important for achieving reward, including auditory and visual stimuli like turning on and off an LED, as well as bar touch. The responses to auditory events depended on the tasks and on the context of the tasks. This provides support for the idea that neuronal representations in PFC are flexible and can be related to the behavioral meaning of stimuli. We also found that engaging in the tasks and holding information in auditory WM were associated with persistent changes of slow potentials, both of which are essential for auditory goal-directed behaviors. Our study, on a single hemisphere in a single monkey, reveals roles of PFC in auditory goal-directed behaviors similar to those in visual goal-directed behaviors, suggesting that functions of PFC in goal-directed behaviors are probably common across the auditory and visual modality. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. MRI volumetry of prefrontal cortex

    Science.gov (United States)

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

    1995-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Jun Xia; Minjie Yang; Yi Lei; Yicheng Zhou

    2010-01-01

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

  4. Plasticity in the Prefrontal Cortex of Adult Rats

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    Bryan eKolb

    2015-02-01

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

  5. [Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis].

    Science.gov (United States)

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Karádi, Zoltán

    2017-05-01

    The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. The functional significance of these chemosensory neurons was to be elucidated. Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

  6. Characterization of excitatory and inhibitory neuron activation in the mouse medial prefrontal cortex following palatable food ingestion and food driven exploratory behavior

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    Ronald P Gaykema

    2014-07-01

    Full Text Available The medial prefrontal cortex (mPFC is implicated in aspects of executive function, that include the modulation of attentional and memory processes involved in goal selection. Food-seeking behavior has been shown to involve activation of the mPFC, both during the execution of strategies designed to obtain food and during the consumption of food itself. As these behaviors likely require differential engagement of the prefrontal cortex, we hypothesized that the pattern of neuronal activation would also be behavior dependent. In this study we describe, for the first time, the expression of Fos in different layers and cell types of the infralimbic/dorsal peduncular (IL/DP and prelimbic/anterior cingulate (PL/AC subdivisions of mouse mPFC following both the consumption of palatable food and following exploratory activity of the animal directed at obtaining food reward. While both manipulations led to increases of Fos expression in principal excitatory neurons relative to control, food-directed exploratory activity produced a significantly greater increase in Fos expression than observed in the food intake condition. Consequently, we hypothesized that mPFC interneuron activation would also be differentially engaged by these manipulations. Interestingly, Fos expression patterns differed substantially between treatments and interneuron subtype, illustrating how the differential engagement of subsets of mPFC interneurons depends on the behavioral state. In our experiments, both vasoactive intestinal peptide- and parvalbumin-expressing neurons showed enhanced Fos expression only during the food-dependent exploratory task and not during food intake. Conversely, elevations in arcuate and paraventricular hypothalamic fos expression were only observed following food intake and not following food driven exploration. Our data suggest that activation of select mPFC interneurons may be required to support high cognitive demand states while being dispensable during

  7. Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial Prefrontal Cortex-Basolateral Complex of Amygdala Projection Neurons in Infralimbic and Prelimbic Cortices.

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    Song, Chenghui; Ehlers, Vanessa L; Moyer, James R

    2015-09-30

    Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted extinction of trace fear conditioning. Significance statement: Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel combination of electrophysiological recordings from fluorescently labeled mPFC-to-amygdala projection neurons in rats with acquisition and extinction of trace fear conditioning to determine how

  8. Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food seeking behavior while reducing impulsivity in the absence of an effect on food intake

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    Daniel McAllister Warthen

    2016-03-01

    Full Text Available The medial prefrontal cortex (mPFC is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons, which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting pyramidal neurons in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using Designer Receptors Exclusively Activated by Designer Drugs (DREADD enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects in affect and food intake. Specifically, activation of mPFC pyramidal neurons enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC pyramidal neurons had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control.

  9. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

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    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  10. Higher Order Spike Synchrony in Prefrontal Cortex during visual memory

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    Gordon ePipa

    2011-06-01

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

  11. Data file of a deep proteome analysis of the prefrontal cortex in aged mice with progranulin deficiency or neuronal overexpression of progranulin.

    Science.gov (United States)

    Heidler, Juliana; Hardt, Stefanie; Wittig, Ilka; Tegeder, Irmgard

    2016-12-01

    Progranulin deficiency is associated with neurodegeneration in humans and in mice. The mechanisms likely involve progranulin-promoted removal of protein waste via autophagy. We performed a deep proteomic screen of the pre-frontal cortex in aged (13-15 months) female progranulin-deficient mice (GRN -/- ) and mice with inducible neuron-specific overexpression of progranulin (SLICK-GRN-OE) versus the respective control mice. Proteins were extracted and analyzed per liquid chromatography/mass spectrometry (LC/MS) on a Thermo Scientific™ Q Exactive Plus equipped with an ultra-high performance liquid chromatography unit and a Nanospray Flex Ion-Source. Full Scan MS-data were acquired using Xcalibur and raw files were analyzed using the proteomics software Max Quant. The mouse reference proteome set from uniprot (June 2015) was used to identify peptides and proteins. The DiB data file is a reduced MaxQuant output and includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ) values of each sample. Differences in protein expression in genotypes are presented in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

  12. Data file of a deep proteome analysis of the prefrontal cortex in aged mice with progranulin deficiency or neuronal overexpression of progranulin

    Directory of Open Access Journals (Sweden)

    Juliana Heidler

    2016-12-01

    Full Text Available Progranulin deficiency is associated with neurodegeneration in humans and in mice. The mechanisms likely involve progranulin-promoted removal of protein waste via autophagy. We performed a deep proteomic screen of the pre-frontal cortex in aged (13–15 months female progranulin-deficient mice (GRN−/− and mice with inducible neuron-specific overexpression of progranulin (SLICK-GRN-OE versus the respective control mice. Proteins were extracted and analyzed per liquid chromatography/mass spectrometry (LC/MS on a Thermo Scientific™ Q Exactive Plus equipped with an ultra-high performance liquid chromatography unit and a Nanospray Flex Ion-Source. Full Scan MS-data were acquired using Xcalibur and raw files were analyzed using the proteomics software Max Quant. The mouse reference proteome set from uniprot (June 2015 was used to identify peptides and proteins. The DiB data file is a reduced MaxQuant output and includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ values of each sample. Differences in protein expression in genotypes are presented in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

  13. Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.

    Science.gov (United States)

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

    2015-10-15

    The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (¹H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla ¹H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement

  14. Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Dominik Strzelecki

    2015-10-01

    Full Text Available The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (1H-NMR spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA; mI, myo-inositol; Cr, creatine; Cho, choline in the left dorso-lateral prefrontal cortex (DLPFC in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients or placebo (25 patients for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla 1H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS. The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA and neurogilal activity (mI with simultaneous

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

    Science.gov (United States)

    Hasegawa, I

    2000-01-01

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

  16. Neural correlates of memory retrieval in the prefrontal cortex.

    Science.gov (United States)

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

    2006-08-01

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

  17. Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons

    Science.gov (United States)

    Park, Junchol

    2017-01-01

    Actions motivated by rewards are often associated with risk of punishment. Little is known about the neural representation of punishment risk during reward-seeking behavior. We modeled this circumstance in rats by designing a task where actions were consistently rewarded but probabilistically punished. Spike activity and local field potentials were recorded during task performance simultaneously from VTA and mPFC, two reciprocally connected regions implicated in reward-seeking and aversive behaviors. At the single unit level, we found that ensembles of putative dopamine and non-dopamine VTA neurons and mPFC neurons encode the relationship between action and punishment. At the network level, we found that coherent theta oscillations synchronize VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment probability, suggesting that during reward-seeking actions, risk of punishment diminishes VTA-driven neural synchrony between the two regions. PMID:29058673

  18. Neonatal Stress Has a Long-Lasting Sex-Dependent Effect on Anxiety-Like Behavior and Neuronal Morphology in the Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    de Melo, Silvana Regina; de David Antoniazzi, Caren Tatiane; Hossain, Shakhawat; Kolb, Bryan

    2018-01-01

    The long-lasting effects of early stress on brain development have been well studied. Recent evidence indicates that males and females respond differently to the same stressor. We examined the chronic effects of daily maternal separation (MS) on behavior and cerebral morphology in both male and female rats. Cognitive and anxiety-like behaviors were evaluated, and neuroplastic changes in 2 subregions of the prefrontal cortex (dorsal agranular insular cortex [AID] and cingulate cortex [Cg3]) and hippocampus (CA1 and dentate gyrus) were measured in adult male and female rats. The animals were subjected to MS on postnatal day (P) 3-14 for 3 h per day. Cognitive and emotional behaviors were assessed in the object/context mismatch task, elevated plus maze, and locomotor activity test in early adulthood (P87-P95). Anatomical assessments were performed in the prefrontal cortex (i.e., cortical thickness and spine density) and hippocampus (i.e., spine density). Sex-dependent effects were observed. MS increased anxiety-related behavior only in males, whereas locomotor activity was higher in females, with no effects on cognition. MS decreased spine density in the AID and increased spine density in the CA1 area in males. Females exhibited an increase in spine density in the Cg3. Our findings confirm previous work that found that MS causes long-term behavioral and anatomical effects, and these effects were dependent on sex and the duration of MS stress. © 2018 S. Karger AG, Basel.

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

    Science.gov (United States)

    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…

  20. An integrative theory of prefrontal cortex function.

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    Miller, E K; Cohen, J D

    2001-01-01

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

  1. The role of prefrontal cortex in psychopathy

    Science.gov (United States)

    Koenigs, Michael

    2014-01-01

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

  2. Opposite effects of low and high doses of Abeta42 on electrical network and neuronal excitability in the rat prefrontal cortex.

    Science.gov (United States)

    Wang, Yun; Zhang, Guangping; Zhou, Hongwei; Barakat, Amey; Querfurth, Henry

    2009-12-21

    Changes in neuronal synchronization have been found in patients and animal models of Alzheimer's disease (AD). Synchronized behaviors within neuronal networks are important to such complex cognitive processes as working memory. The mechanisms behind these changes are not understood but may involve the action of soluble beta-amyloid (Abeta) on electrical networks. In order to determine if Abeta can induce changes in neuronal synchronization, the activities of pyramidal neurons were recorded in rat prefrontal cortical (PFC) slices under calcium-free conditions using multi-neuron patch clamp technique. Electrical network activities and synchronization among neurons were significantly inhibited by low dose Abeta42 (1 nM) and initially by high dose Abeta42 (500 nM). However, prolonged application of high dose Abeta42 resulted in network activation and tonic firing. Underlying these observations, we discovered that prolonged application of low and high doses of Abeta42 induced opposite changes in action potential (AP)-threshold and after-hyperpolarization (AHP) of neurons. Accordingly, low dose Abeta42 significantly increased the AP-threshold and deepened the AHP, making neurons less excitable. In contrast, high dose Abeta42 significantly reduced the AP-threshold and shallowed the AHP, making neurons more excitable. These results support a model that low dose Abeta42 released into the interstitium has a physiologic feedback role to dampen electrical network activity by reducing neuronal excitability. Higher concentrations of Abeta42 over time promote supra-synchronization between individual neurons by increasing their excitability. The latter may disrupt frontal-based cognitive processing and in some cases lead to epileptiform discharges.

  3. Opposite effects of low and high doses of Abeta42 on electrical network and neuronal excitability in the rat prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available Changes in neuronal synchronization have been found in patients and animal models of Alzheimer's disease (AD. Synchronized behaviors within neuronal networks are important to such complex cognitive processes as working memory. The mechanisms behind these changes are not understood but may involve the action of soluble beta-amyloid (Abeta on electrical networks. In order to determine if Abeta can induce changes in neuronal synchronization, the activities of pyramidal neurons were recorded in rat prefrontal cortical (PFC slices under calcium-free conditions using multi-neuron patch clamp technique. Electrical network activities and synchronization among neurons were significantly inhibited by low dose Abeta42 (1 nM and initially by high dose Abeta42 (500 nM. However, prolonged application of high dose Abeta42 resulted in network activation and tonic firing. Underlying these observations, we discovered that prolonged application of low and high doses of Abeta42 induced opposite changes in action potential (AP-threshold and after-hyperpolarization (AHP of neurons. Accordingly, low dose Abeta42 significantly increased the AP-threshold and deepened the AHP, making neurons less excitable. In contrast, high dose Abeta42 significantly reduced the AP-threshold and shallowed the AHP, making neurons more excitable. These results support a model that low dose Abeta42 released into the interstitium has a physiologic feedback role to dampen electrical network activity by reducing neuronal excitability. Higher concentrations of Abeta42 over time promote supra-synchronization between individual neurons by increasing their excitability. The latter may disrupt frontal-based cognitive processing and in some cases lead to epileptiform discharges.

  4. Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats.

    Science.gov (United States)

    Abekawa, Tomohiro; Ito, Koki; Nakagawa, Shin; Koyama, Tsukasa

    2007-06-01

    Neurodevelopmental deficits of parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)ergic interneurons in prefrontal cortex have been reported in schizophrenia. Glutamate influences the proliferation of this type of interneuron by an N-methyl-D-aspartate (NMDA)-receptor-mediated mechanism. The present study hypothesized that prenatal blockade of NMDA receptors would disrupt GABAergic neurodevelopment, resulting in differences in effects on behavioral responses to a noncompetitive NMDA antagonist, phencyclidine (PCP), and a dopamine releaser, methamphetamine (METH). GABAergic neurons were immunohistochemically stained with parvalbumin antibody. Psychostimulant-induced hyperlocomotion was measured using an infrared sensor. Prenatal exposure (E15-E18) to the NMDA receptor antagonist MK-801 reduced the density of parvalbumin-immunoreactive neurons in rat medial prefrontal cortex on postnatal day 63 (P63) and enhanced PCP-induced hyperlocomotion but not the acute effects of METH on P63 or the development of behavioral sensitization. Prenatal exposure to MK-801 reduced the number of parvalbumin-immunoreactive neurons even on postnatal day 35 (P35) and did not enhance PCP-induced hyperlocomotion, the acute effects of METH on P35, or the development of behavioral sensitization to METH. These findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring. GABAergic deficit is unrelated to the effects of METH. This GABAergic neurodevelopmental disruption and the enhanced PCP-induced hyperlocomotion in adult offspring prenatally exposed to MK-801 may prove useful as a new model of the neurodevelopmental process of pathogenesis of treatment-resistant schizophrenia via an NMDA-receptor-mediated hypoglutamatergic mechanism.

  5. Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

    Science.gov (United States)

    González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

    2016-02-01

    The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  7. Hyper-Connectivity and Hyper-Plasticity in the Medial Prefrontal Cortex in the Valproic Acid Animal Model of Autism

    OpenAIRE

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

    The prefrontal cortex has been extensively implicated in autism to explain deficits in executive and other higher-order functions related to cognition, language, sociability and emotion. The possible changes at the level of the neuronal microcircuit are however not known. We studied microcircuit alterations in the prefrontal cortex in the valproic acid rat model of autism and found that the layer 5 pyramidal neurons are connected to significantly more neighbouring neurons than in controls. Th...

  8. Amodal processing in human prefrontal cortex.

    Science.gov (United States)

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

    2013-07-10

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

  9. Reward Inference by Primate Prefrontal and Striatal Neurons

    OpenAIRE

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Daniel W. Sparks

    2018-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  13. Khat distorts the prefrontal cortex histology and function of adult ...

    African Journals Online (AJOL)

    Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive ...

  14. Responses of prefrontal multisensory neurons to mismatching faces and vocalizations.

    Science.gov (United States)

    Diehl, Maria M; Romanski, Lizabeth M

    2014-08-20

    Social communication relies on the integration of auditory and visual information, which are present in faces and vocalizations. Evidence suggests that the integration of information from multiple sources enhances perception compared with the processing of a unimodal stimulus. Our previous studies demonstrated that single neurons in the ventrolateral prefrontal cortex (VLPFC) of the rhesus monkey (Macaca mulatta) respond to and integrate conspecific vocalizations and their accompanying facial gestures. We were therefore interested in how VLPFC neurons respond differentially to matching (congruent) and mismatching (incongruent) faces and vocalizations. We recorded VLPFC neurons during the presentation of movies with congruent or incongruent species-specific facial gestures and vocalizations as well as their unimodal components. Recordings showed that while many VLPFC units are multisensory and respond to faces, vocalizations, or their combination, a subset of neurons showed a significant change in neuronal activity in response to incongruent versus congruent vocalization movies. Among these neurons, we typically observed incongruent suppression during the early stimulus period and incongruent enhancement during the late stimulus period. Incongruent-responsive VLPFC neurons were both bimodal and nonlinear multisensory, fostering their ability to respond to changes in either modality of a face-vocalization stimulus. These results demonstrate that ventral prefrontal neurons respond to changes in either modality of an audiovisual stimulus, which is important in identity processing and for the integration of multisensory communication information. Copyright © 2014 the authors 0270-6474/14/3411233-11$15.00/0.

  15. DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age

    Directory of Open Access Journals (Sweden)

    Alexey Kozlenkov

    2017-05-01

    Full Text Available We employed Illumina 450 K Infinium microarrays to profile DNA methylation (DNAm in neuronal nuclei separated by fluorescence-activated sorting from the postmortem orbitofrontal cortex (OFC of heroin users who died from heroin overdose (N = 37, suicide completers (N = 22 with no evidence of heroin use and from control subjects who did not abuse illicit drugs and died of non-suicide causes (N = 28. We identified 1298 differentially methylated CpG sites (DMSs between heroin users and controls, and 454 DMSs between suicide completers and controls (p < 0.001. DMSs and corresponding genes (DMGs in heroin users showed significant differences in the preferential context of hyper and hypo DM. HyperDMSs were enriched in gene bodies and exons but depleted in promoters, whereas hypoDMSs were enriched in promoters and enhancers. In addition, hyperDMGs showed preference for genes expressed specifically by glutamatergic as opposed to GABAergic neurons and enrichment for axonogenesis- and synaptic-related gene ontology categories, whereas hypoDMGs were enriched for transcription factor activity- and gene expression regulation-related terms. Finally, we found that the DNAm-based “epigenetic age” of neurons from heroin users was younger than that in controls. Suicide-related results were more difficult to interpret. Collectively, these findings suggest that the observed DNAm differences could represent functionally significant marks of heroin-associated plasticity in the OFC.

  16. Inhibitory Gating of Basolateral Amygdala Inputs to the Prefrontal Cortex.

    Science.gov (United States)

    McGarry, Laura M; Carter, Adam G

    2016-09-07

    Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC. We find that BLA inputs preferentially target layer 2 corticoamygdala over neighboring corticostriatal neurons. However, these inputs make even stronger connections onto neighboring parvalbumin and somatostatin expressing interneurons. Inhibitory connections from these two populations of interneurons are also much stronger onto corticoamygdala neurons. Consequently, BLA inputs are able to drive robust feedforward inhibition via two parallel interneuron pathways. Moreover, the contributions of these interneurons shift during repetitive activity, due to differences in short-term synaptic dynamics. Thus, parvalbumin interneurons are activated at the start of stimulus trains, whereas somatostatin interneuron activation builds during these trains. Together, these results reveal how the BLA impacts the PFC through a complex interplay of direct excitation and feedforward inhibition. They also highlight the roles of targeted connections onto multiple projection neurons and interneurons in this cortical circuit. Our findings provide a mechanistic understanding for how the BLA can influence the PFC circuit, with important implications for how this circuit participates in the regulation of emotion. The prefrontal cortex (PFC) and basolateral amygdala (BLA) interact to control emotional behaviors. Here we show that BLA inputs elicit direct excitation and feedforward inhibition of layer 2 projection neurons in infralimbic PFC. BLA inputs are much stronger at corticoamygdala neurons compared

  17. Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

    Directory of Open Access Journals (Sweden)

    Saha Subhash

    2003-10-01

    Full Text Available Abstract Background Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal. Results We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

    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…

  20. Layer-specific modulation of the prefrontal cortex by nicotinic acetylcholine receptors

    NARCIS (Netherlands)

    Poorthuis, R.B.; Bloem, B.; Schak, B.; Wester, J.; de Kock, C.P.J.; Mansvelder, H.D.

    2013-01-01

    Acetylcholine signaling through nicotinic receptors (nAChRs) in the prefrontal cortex (PFC) is crucial for attention. Nicotinic AChRs are expressed on glutamatergic inputs to layer V (LV) cells and on LV interneurons and LVI pyramidal neurons. Whether PFC layers are activated by nAChRs to a similar

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

    Science.gov (United States)

    Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

    2008-07-16

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

  2. The Development of the Ventral Prefrontal Cortex and Social Flexibility

    Science.gov (United States)

    Nelson, Eric E.; Guyer, Amanda E.

    2011-01-01

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

  3. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

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

    2017-11-17

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

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

    Science.gov (United States)

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

    2010-11-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  6. Functional inactivation of hypocretin 1 receptors in the medial prefrontal cortex affects the pyramidal neuron activity and gamma oscillations: An in vivo multiple-channel single-unit recording study.

    Science.gov (United States)

    He, C; Chen, Q-H; Ye, J-N; Li, C; Yang, L; Zhang, J; Xia, J-X; Hu, Z-A

    2015-06-25

    The hypocretin signaling is thought to play a critical role in maintaining wakefulness via stimulating the subcortical arousal pathways. Although the cortical areas, including the medial prefrontal cortex (mPFC), receive dense hypocretinergic fibers and express its receptors, it remains unclear whether the hypocretins can directly regulate the neural activity of the mPFC in vivo. In the present study, using multiple-channel single-unit recording study, we found that infusion of the SB-334867, a blocker for the Hcrtr1, beside the recording sites within the mPFC substantially exerted an inhibitory effect on the putative pyramidal neuron (PPN) activity in naturally behaving rats. In addition, functional blockade of the Hcrtr1 also selectively reduced the power of the gamma oscillations. The PPN activity and the power of the neural oscillations were not affected after microinjection of the TCS-OX2-29, a blocker for the Hcrtr2, within the mPFC. Together, these data indicate that endogenous hypocretins acting on the Hcrtr1 are required for the normal neural activity in the mPFC in vivo, and thus might directly contribute cortical arousal and mPFC-dependent cognitive processes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Interplay of hippocampus and prefrontal cortex in memory

    Science.gov (United States)

    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

  8. Integration of auditory and visual communication information in the primate ventrolateral prefrontal cortex.

    Science.gov (United States)

    Sugihara, Tadashi; Diltz, Mark D; Averbeck, Bruno B; Romanski, Lizabeth M

    2006-10-25

    The integration of auditory and visual stimuli is crucial for recognizing objects, communicating effectively, and navigating through our complex world. Although the frontal lobes are involved in memory, communication, and language, there has been no evidence that the integration of communication information occurs at the single-cell level in the frontal lobes. Here, we show that neurons in the macaque ventrolateral prefrontal cortex (VLPFC) integrate audiovisual communication stimuli. The multisensory interactions included both enhancement and suppression of a predominantly auditory or a predominantly visual response, although multisensory suppression was the more common mode of response. The multisensory neurons were distributed across the VLPFC and within previously identified unimodal auditory and visual regions (O'Scalaidhe et al., 1997; Romanski and Goldman-Rakic, 2002). Thus, our study demonstrates, for the first time, that single prefrontal neurons integrate communication information from the auditory and visual domains, suggesting that these neurons are an important node in the cortical network responsible for communication.

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

    Directory of Open Access Journals (Sweden)

    Tania Rinaldi

    2008-10-01

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

  10. The amygdala and ventromedial prefrontal cortex in morality and psychopathy.

    Science.gov (United States)

    Blair, R J R

    2007-09-01

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

  11. Monetary reward activates human prefrontal cortex

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  12. Reward inference by primate prefrontal and striatal neurons.

    Science.gov (United States)

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

    2014-01-22

    The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.

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

    Science.gov (United States)

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

    1995-01-01

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

  14. Acute pharmacogenetic activation of medial prefrontal cortex ...

    Indian Academy of Sciences (India)

    Sthitapranjya Pati

    2018-01-24

    Jan 24, 2018 ... Exclusively Activated by Designer Drugs (DREADDs) have provided novel ... ad libitum access to food and water. ... testing. 2.3 Drug treatment and behavioural tests .... IL cortex (figure 3E, two-way ANOVA: interaction effect,.

  15. Capacity-speed relationships in prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Vivek Prabhakaran

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

  16. Exon microarray analysis of human dorsolateral prefrontal cortex in alcoholism.

    Science.gov (United States)

    Manzardo, Ann M; Gunewardena, Sumedha; Wang, Kun; Butler, Merlin G

    2014-06-01

    Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function, and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC; Brodmann area 9) of 7 adult alcoholic (6 males, 1 female, mean age 49 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using quantitative reverse transcription polymerase chain reaction, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN), and signaling (e.g., RASGRP3, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease and development including cellular assembly and organization impacting on psychological disorders. Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation, and signaling that targets white matter of the brain. Copyright © 2014 by the Research Society on Alcoholism.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  18. khat distorts the prefrontal cortex histology and function of adult

    African Journals Online (AJOL)

    2018-02-28

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

  19. Comparison of (stereotactic) parcellations in mouse prefrontal cortex

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Science.gov (United States)

    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…

  2. Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior

    DEFF Research Database (Denmark)

    Brumback, A C; Ellwood, I T; Kjaerby, C

    2017-01-01

    Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior...... in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered...... SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially...

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

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

    2015-08-01

    The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. Copyright © 2015 the American Physiological Society.

  5. Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.

    Science.gov (United States)

    Benn, Abigail; Barker, Gareth R I; Stuart, Sarah A; Roloff, Eva V L; Teschemacher, Anja G; Warburton, E Clea; Robinson, Emma S J

    2016-05-04

    Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement. Copyright © 2016 Benn et al.

  6. Cadherin-8 expression, synaptic localization, and molecular control of neuronal form in prefrontal corticostriatal circuits.

    Science.gov (United States)

    Friedman, Lauren G; Riemslagh, Fréderike W; Sullivan, Josefa M; Mesias, Roxana; Williams, Frances M; Huntley, George W; Benson, Deanna L

    2015-01-01

    Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex-striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin-8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real-time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High-resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self-avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. © 2014 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Plakke, Bethany; Hwang, Jaewon; Romanski, Lizabeth M

    2015-07-01

    The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that

  8. A dorsolateral prefrontal cortex semi-automatic segmenter

    Science.gov (United States)

    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

  9. Prefrontal Cortex, Emotion, and Approach/Withdrawal Motivation.

    Science.gov (United States)

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

    2008-01-01

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

  10. Prefrontal Neuronal Excitability Maintains Cocaine-Associated Memory During Retrieval

    Directory of Open Access Journals (Sweden)

    James M. Otis

    2018-06-01

    Full Text Available Presentation of drug-associated cues provokes craving and drug seeking, and elimination of these associative memories would facilitate recovery from addiction. Emotionally salient memories are maintained during retrieval, as particular pharmacologic or optogenetic perturbations of memory circuits during retrieval, but not after, can induce long-lasting memory impairments. For example, in rats, inhibition of noradrenergic beta-receptors, which control intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL-mPFC can cause long-term memory impairments that prevent subsequent cocaine-induced reinstatement. The physiologic mechanisms that allow noradrenergic signaling to maintain drug-associated memories during retrieval, however, are unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral neuropharmacology in vivo to evaluate the mechanisms that maintain drug-associated memory during retrieval in rats. Consistent with previous studies, we find that cocaine experience increases the intrinsic excitability of pyramidal neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity positively predicts the retrieval of a cocaine-induced conditioned place preference (CPP memory, suggesting that such plasticity may contribute to drug-associated memory retrieval. In further support of this, we find that pharmacological blockade of a cAMP-dependent signaling cascade, which allows noradrenergic signaling to elevate neuronal excitability, is required for memory maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability during memory retrieval not only leads to long-term deficits in the memory, but this memory deficit provides protection against subsequent cocaine-induced reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability maintains a cocaine-associated memory during retrieval and suggest a unique mechanism whereby drug-associated memories could be targeted

  11. Prefrontal Cortex and Social Cognition in Mouse and Man

    Science.gov (United States)

    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

  12. Ventromedial prefrontal cortex, adding value to autobiographical memories

    OpenAIRE

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

    2016-01-01

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

  13. Prefrontal cortex activity during swallowing in dysphagia patients.

    Science.gov (United States)

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

    2018-05-24

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

  14. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

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

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2014-02-01

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

  16. Effects of decreased inhibition on synaptic plasticity and dendritic morphology in the juvenile prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Xanthippi Konstantoudaki

    2014-03-01

    Full Text Available Excitation-inhibition balance is critical for maintaining proper functioning of the cerebral cortex, as evident from electrophysiological and modeling studies, and it is also important for animal behavior (Yizhar et al., 2011. In the cerebral cortex, excitation is provided by glutamate release from pyramidal neurons, while inhibition is provided by GABA release from several types of interneurons. Many neuropsychiatric disorders, such as epilepsy, anxiety, schizophrenia and autism exhibit an imbalance between the excitatory and inhibitory mechanisms of cortical circuits within key brain regions as prefrontal cortex or hippocampus, primarily through dysfunctions in the inhibitory system (Lewis, Volk, & Hashimoto, 2003; Marín, 2012 Given the significant role of GABAergic inhibition in shaping proper function of the cerebral cortex, we used a mouse model of developmentally decreased GABAergic inhibition in order to examine its effects in network properties, namely basal synaptic transmission, synaptic plasticity and dendritic morphology of pyramidal neurons. For our study, we used mice (postnatal day 20-30 in which the Rac1 protein was deleted from Nkx2.1-expressing neurons (Vidaki et al., 2012, (Rac1fl/flNkx2.1 +/cre referred as Rac1 KO mice, and heterozygous (Rac1+/flNkx2.1 +/cre or control (Rac1+/flNkx2.1 +/+ mice. The specific ablation of Rac1 protein from NKx2.1-expressing MGE-derived progenitors leads to a perturbation of their cell cycle exit resulting in decreased number of interneurons in the cortex(Vidaki et al, 2012. We prepared brain slices from the prefrontal cortex and recorded field excitatory postsynaptic potentials (fEPSPs from layer II neurons while stimulating axons in layer II. We find that the evoked fEPSPs are decreased in Rac1 KO mice compared to Rac1 heterozygous or control mice. This could suggest that the decreased GABAergic inhibition causes network alterations that result in reduced glutamatergic function. Furthermore

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

    Science.gov (United States)

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

    2016-06-15

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

  18. Short-term environmental enrichment exposure induces proliferation and maturation of doublecortin-positive cells in the prefrontal cortex

    Science.gov (United States)

    Fan, Chunling; Zhang, Mengqi; Shang, Lei; Cynthia, Ngobe Akume; Li, Zhi; Yang, Zhenyu; Chen, Dan; Huang, Jufang; Xiong, Kun

    2014-01-01

    Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine (a marker of cell proliferation), c-Fos (a marker of cell viability) and NeuN (a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs. PMID:25206818

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

    Science.gov (United States)

    Chang, Chun-Hui

    2017-07-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    NARCIS (Netherlands)

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

    1987-01-01

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

  2. Functional organization and visual representations in human ventral lateral prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Annie Wai Yiu Chan

    2013-07-01

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

  3. Changes in prefrontal neuronal activity after learning to perform a spatial working memory task.

    Science.gov (United States)

    Qi, Xue-Lian; Meyer, Travis; Stanford, Terrence R; Constantinidis, Christos

    2011-12-01

    The prefrontal cortex is considered essential for learning to perform cognitive tasks though little is known about how the representation of stimulus properties is altered by learning. To address this issue, we recorded neuronal activity in monkeys before and after training on a task that required visual working memory. After the subjects learned to perform the task, we observed activation of more prefrontal neurons and increased activity during working memory maintenance. The working memory-related increase in firing rate was due mostly to regular-spiking putative pyramidal neurons. Unexpectedly, the selectivity of neurons for stimulus properties and the ability of neurons to discriminate between stimuli decreased as the information about stimulus properties was apparently present in neural firing prior to training and neuronal selectivity degraded after training in the task. The effect was robust and could not be accounted for by differences in sampling sites, selection of neurons, level of performance, or merely the elapse of time. The results indicate that, in contrast to the effects of perceptual learning, mastery of a cognitive task degrades the apparent stimulus selectivity as neurons represent more abstract information related to the task. This effect is countered by the recruitment of more neurons after training.

  4. Monoaminergic modulation of emotional impact in the inferomedial prefrontal cortex

    DEFF Research Database (Denmark)

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    of the standard Empathy Picture System on a scale from +3 to -3. We then used regression analysis to identify sites in the ventromedial prefrontal cortex at which the two separately acquired measures, blood flow change and emotional impact of images, correlated significantly. The regression analysis identified......People assess the impact of emotionally loaded images differently. We define this impact as the average difference between individual ratings of standardized "pleasant" and "unpleasant" images. To determine the neuroanatomical correlate of a hypothetical interaction between emotional impact...... cortex underwent deactivation in proportion to a separately rated emotional impact of a stimulus. We propose a specific pharmacodynamic mechanism that explains the correlation between the emotional impact and the effect of a serotonin-noradrenaline reuptake inhibitor on cerebral blood flow....

  5. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia.

    Science.gov (United States)

    Zugman, André; Gadelha, Ary; Assunção, Idaiane; Sato, João; Ota, Vanessa K; Rocha, Deyvis L; Mari, Jair J; Belangero, Sintia I; Bressan, Rodrigo A; Brietzke, Elisa; Jackowski, Andrea P

    2013-08-01

    Treatment resistance affects up to one third of patients with schizophrenia (SCZ). A better understanding of its biological underlying processes could improve treatment. The aim of this study was to compare cortical thickness between non-resistant SCZ (NR-SCZ), treatment-resistant SCZ (TR-SCZ) patients and healthy controls (HC). Structural MRI scans were obtained from 3 groups of individuals: 61 treatment resistant SCZ individuals, 67 non-resistant SCZ and 80 healthy controls. Images were analyzed using cortical surface modelling (implemented in freesurfer package) to identify group differences in cortical thickness. Statistical significant differences were identified using Monte-Carlo simulation method with a corrected p-cluster<0.01. Patients in the TR-SCZ group showed a widespread reduction in cortical thickness in frontal, parietal, temporal and occipital regions bilaterally. NR-SCZ group had reduced cortex in two regions (left superior frontal cortex and left caudal middle frontal cortex). TR-SCZ group also showed decreased thickness in the left dorsolateral prefrontal cortex (DLPFC) when compared with patients from NR-SCZ group. The reduction in cortical thickness in DLPFC indicates a more severe form of the disease or a specific finding for this group. Alterations in this region should be explored as a putative marker for treatment resistance. Prospective studies, with individuals being followed from first episode psychosis until refractoriness is diagnosed, are needed to clarify these hypotheses. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-06-24

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

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

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    Anders H. Andersen

    2015-01-01

    Full Text Available Parkinson’s disease (PD is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD patients. Participants included 18 ndPD patients (11 men, 7 women and 10 dPD patients (7 men, 3 women. Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN. DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients.

  9. Impaired Wnt Signaling in the Prefrontal Cortex of Alzheimer's Disease

    DEFF Research Database (Denmark)

    Folke, Jonas; Pakkenberg, Bente; Brudek, Tomasz

    2018-01-01

    Wnt pathway is involved in synaptic plasticity and neuronal survival, and alterations in Wnt signaling have previously been reported both in aging and neurodegenerative diseases, including Alzheimer's disease (AD). This study sought to evaluate Wnt signaling pathway interplay integrity across......, in addition to downstream effects associated with disease progression and cognitive decline. This study is the first that comprehensively evaluates Wnt signaling pathway in the prefrontal cortical lobe structures of AD brains, in relation to age-related coordinated Wnt signaling changes. Our findings further...

  10. Adaptive Encoding of Outcome Prediction by Prefrontal Cortex Ensembles Supports Behavioral Flexibility.

    Science.gov (United States)

    Del Arco, Alberto; Park, Junchol; Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

    2017-08-30

    The prefrontal cortex (PFC) is thought to play a critical role in behavioral flexibility by monitoring action-outcome contingencies. How PFC ensembles represent shifts in behavior in response to changes in these contingencies remains unclear. We recorded single-unit activity and local field potentials in the dorsomedial PFC (dmPFC) of male rats during a set-shifting task that required them to update their behavior, among competing options, in response to changes in action-outcome contingencies. As behavior was updated, a subset of PFC ensembles encoded the current trial outcome before the outcome was presented. This novel outcome-prediction encoding was absent in a control task, in which actions were rewarded pseudorandomly, indicating that PFC neurons are not merely providing an expectancy signal. In both control and set-shifting tasks, dmPFC neurons displayed postoutcome discrimination activity, indicating that these neurons also monitor whether a behavior is successful in generating rewards. Gamma-power oscillatory activity increased before the outcome in both tasks but did not differentiate between expected outcomes, suggesting that this measure is not related to set-shifting behavior but reflects expectation of an outcome after action execution. These results demonstrate that PFC neurons support flexible rule-based action selection by predicting outcomes that follow a particular action. SIGNIFICANCE STATEMENT Tracking action-outcome contingencies and modifying behavior when those contingencies change is critical to behavioral flexibility. We find that ensembles of dorsomedial prefrontal cortex neurons differentiate between expected outcomes when action-outcome contingencies change. This predictive mode of signaling may be used to promote a new response strategy at the service of behavioral flexibility. Copyright © 2017 the authors 0270-6474/17/378363-11$15.00/0.

  11. Dampened dopamine-mediated neuromodulation in prefrontal cortex of fragile X mice.

    Science.gov (United States)

    Paul, Kush; Venkitaramani, Deepa V; Cox, Charles L

    2013-02-15

    Fragile X syndrome (FXS) is the most common form of inheritable mental retardation caused by transcriptional silencing of the Fmr1 gene resulting in the absence of fragile X mental retardation protein (FMRP). The role of this protein in neurons is complex and its absence gives rise to diverse alterations in neuronal function leading to neurological disorders including mental retardation, hyperactivity, cognitive impairment, obsessive-compulsive behaviour, seizure activity and autism. FMRP regulates mRNA translation at dendritic spines where synapses are formed, and thus the lack of FMRP can lead to disruptions in synaptic transmission and plasticity. Many of these neurological deficits in FXS probably involve the prefrontal cortex, and in this study, we have focused on modulatory actions of dopamine in the medial prefrontal cortex. Our data indicate that dopamine produces a long-lasting enhancement of evoked inhibitory postsynaptic currents (IPSCs) mediated by D1-type receptors seen in wild-type mice; however, such enhancement is absent in the Fmr1 knock-out (Fmr1 KO) mice. The facilitation of IPSCs produced by direct cAMP stimulation was unaffected in Fmr1 KO, but D1 receptor levels were reduced in these animals. Our results show significant disruption of dopaminergic modulation of synaptic transmission in the Fmr1 KO mice and this alteration in inhibitory activity may provide insight into potential targets for the rescue of deficits associated with FXS.

  12. Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear

    DEFF Research Database (Denmark)

    Marek, Roger; Jin, Jingji; Goode, Travis D.

    2018-01-01

    The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished...... fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons...... in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together...

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

    Science.gov (United States)

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

    2017-07-01

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

  14. Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

    Science.gov (United States)

    Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

    2017-12-01

    Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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…

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  17. Bidirectional control of social hierarchy by synaptic efficacy in medial prefrontal cortex.

    Science.gov (United States)

    Wang, Fei; Zhu, Jun; Zhu, Hong; Zhang, Qi; Lin, Zhanmin; Hu, Hailan

    2011-11-04

    Dominance hierarchy has a profound impact on animals' survival, health, and reproductive success, but its neural circuit mechanism is virtually unknown. We found that dominance ranking in mice is transitive, relatively stable, and highly correlates among multiple behavior measures. Recording from layer V pyramidal neurons of the medial prefrontal cortex (mPFC) showed higher strength of excitatory synaptic inputs in mice with higher ranking, as compared with their subordinate cage mates. Furthermore, molecular manipulations that resulted in an increase and decrease in the synaptic efficacy in dorsal mPFC neurons caused an upward and downward movement in the social rank, respectively. These results provide direct evidence for mPFC's involvement in social hierarchy and suggest that social rank is plastic and can be tuned by altering synaptic strength in mPFC pyramidal cells.

  18. An Excitatory Neural Assembly Encodes Short-Term Memory in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Yonglu Tian

    2018-02-01

    Full Text Available Short-term memory (STM is crucial for animals to hold information for a small period of time. Persistent or recurrent neural activity, together with neural oscillations, is known to encode the STM at the cellular level. However, the coding mechanisms at the microcircuitry level remain a mystery. Here, we performed two-photon imaging on behaving mice to monitor the activity of neuronal microcircuitry. We discovered a neuronal subpopulation in the medial prefrontal cortex (mPFC that exhibited emergent properties in a context-dependent manner underlying a STM-like behavior paradigm. These neuronal subpopulations exclusively comprise excitatory neurons and mainly represent a group of neurons with stronger functional connections. Microcircuitry plasticity was maintained for minutes and was absent in an animal model of Alzheimer’s disease (AD. Thus, these results point to a functional coding mechanism that relies on the emergent behavior of a functionally defined neuronal assembly to encode STM.

  19. Brain cells in the avian 'prefrontal cortex' code for features of slot-machine-like gambling.

    Directory of Open Access Journals (Sweden)

    Damian Scarf

    2011-01-01

    Full Text Available Slot machines are the most common and addictive form of gambling. In the current study, we recorded from single neurons in the 'prefrontal cortex' of pigeons while they played a slot-machine-like task. We identified four categories of neurons that coded for different aspects of our slot-machine-like task. Reward-Proximity neurons showed a linear increase in activity as the opportunity for a reward drew near. I-Won neurons fired only when the fourth stimulus of a winning (four-of-a-kind combination was displayed. I-Lost neurons changed their firing rate at the presentation of the first nonidentical stimulus, that is, when it was apparent that no reward was forthcoming. Finally, Near-Miss neurons also changed their activity the moment it was recognized that a reward was no longer available, but more importantly, the activity level was related to whether the trial contained one, two, or three identical stimuli prior to the display of the nonidentical stimulus. These findings not only add to recent neurophysiological research employing simulated gambling paradigms, but also add to research addressing the functional correspondence between the avian NCL and primate PFC.

  20. Prefrontal cortex and somatosensory cortex in tactile crossmodal association: an independent component analysis of ERP recordings.

    Directory of Open Access Journals (Sweden)

    Yixuan Ku

    2007-08-01

    Full Text Available Our previous studies on scalp-recorded event-related potentials (ERPs showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA to the ERP data, we found independent components (ICs located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC and the primary somatosensory cortex (SI. The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex that are involved in sensation and perception of various stimuli.

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

    Science.gov (United States)

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

    2005-11-07

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

  2. An integrative theory of the phasic and tonic modes of dopamine modulation in the prefrontal cortex.

    Science.gov (United States)

    Dreher, Jean-Claude; Burnod, Yves

    2002-01-01

    This paper presents a model of both tonic and phasic dopamine (DA) effects on maintenance of working memory representations in the prefrontal cortex (PFC). The central hypothesis is that DA modulates the efficacy of inputs to prefrontal pyramidal neurons to prevent interferences for active maintenance. Phasic DA release, due to DA neurons discharges, acts at a short time-scale (a few seconds), while the tonic mode of DA release, independent of DA neurons firing, acts at a long time-scale (a few minutes). The overall effect of DA modulation is modeled as a threshold restricting incoming inputs arriving on PFC neurons. Phasic DA release temporary increases this threshold while tonic DA release progressively increases the basal level of this threshold. Thus, unlike the previous gating theory of phasic DA release, proposing that it facilitates incoming inputs at the time of their arrival, the effect of phasic DA release is supposed to restrict incoming inputs during a period of time after DA neuron discharges. The model links the cellular and behavioral levels during performance of a working memory task. It allows us to understand why a critical range of DA D1 receptors stimulation is required for optimal working memory performance and how D1 receptor agonists (respectively antagonists) increase perseverations (respectively distractability). Finally, the model leads to several testable predictions, including that the PFC regulates DA neurons firing rate to adapt to the delay of the task and that increase in tonic DA release may either improve or decrease performance, depending on the level of DA receptors stimulation at the beginning of the task.

  3. Behavioral effects of congenital ventromedial prefrontal cortex malformation

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    Boes Aaron D

    2011-12-01

    Full Text Available Abstract 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.

  4. Sleep deprivation alters valuation signals in the ventromedial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Camilo eLibedinsky

    2011-10-01

    Full Text Available Even a single night of total sleep-deprivation (SD can have dramatic effects on economic decision making. Here we tested the novel hypothesis that SD influences economic decisions by altering the valuation process. Using functional magnetic resonance imaging (fMRI we identified value signals related to the anticipation and the experience of monetary and social rewards (attractive female faces. We then derived decision value signals that were predictive of each participant’s willingness to exchange money for brief views of attractive faces in an independent market task. Strikingly, SD altered decision value signals in ventromedial prefrontal cortex (VMPFC in proportion to the corresponding change in economic preferences. These changes in preference were independent of the effects of SD on attention and vigilance. Our results provide novel evidence that signals in VMPFC track the current state of the individual, and thus reflect not static but constructed preferences.

  5. Levels of conflict in reasoning modulate right lateral prefrontal cortex.

    Science.gov (United States)

    Stollstorff, Melanie; Vartanian, Oshin; Goel, Vinod

    2012-01-05

    Right lateral prefrontal cortex (rlPFC) has previously been implicated in logical reasoning under conditions of conflict. A functional magnetic resonance imaging (fMRI) study was conducted to explore its role in conflict more precisely. Specifically, we distinguished between belief-logic conflict and belief-content conflict, and examined the role of rlPFC under each condition. The results demonstrated that a specific region of rlPFC is consistently activated under both types of conflict. Moreover, the results of a parametric analysis demonstrated that the same region was modulated by the level of conflict contained in reasoning arguments. This supports the idea that this specific region is engaged to resolve conflict, including during deductive reasoning. This article is part of a Special Issue entitled "The Cognitive Neuroscience of Thought". Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Reversal of Cocaine-Associated Synaptic Plasticity in Medial Prefrontal Cortex Parallels Elimination of Memory Retrieval.

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    Otis, James M; Mueller, Devin

    2017-09-01

    Addiction is characterized by abnormalities in prefrontal cortex that are thought to allow drug-associated cues to drive compulsive drug seeking and taking. Identification and reversal of these pathologic neuroadaptations are therefore critical for treatment of addiction. Previous studies using rodents reveal that drugs of abuse cause dendritic spine plasticity in prelimbic medial prefrontal cortex (PL-mPFC) pyramidal neurons, a phenomenon that correlates with the strength of drug-associated memories in vivo. Thus, we hypothesized that cocaine-evoked plasticity in PL-mPFC may underlie cocaine-associated memory retrieval, and therefore disruption of this plasticity would prevent retrieval. Indeed, using patch clamp electrophysiology we find that cocaine place conditioning increases excitatory presynaptic and postsynaptic transmission in rat PL-mPFC pyramidal neurons. This was accounted for by increases in excitatory presynaptic release, paired-pulse facilitation, and increased AMPA receptor transmission. Noradrenergic signaling is known to maintain glutamatergic plasticity upon reactivation of modified circuits, and we therefore next determined whether inhibition of noradrenergic signaling during memory reactivation would reverse the cocaine-evoked plasticity and/or disrupt the cocaine-associated memory. We find that administration of the β-adrenergic receptor antagonist propranolol before memory retrieval, but not after (during memory reconsolidation), reverses the cocaine-evoked presynaptic and postsynaptic modifications in PL-mPFC and causes long-lasting memory impairments. Taken together, these data reveal that cocaine-evoked synaptic plasticity in PL-mPFC is reversible in vivo, and suggest a novel strategy that would allow normalization of prefrontal circuitry in addiction.

  7. Tangram solved? Prefrontal cortex activation analysis during geometric problem solving.

    Science.gov (United States)

    Ayaz, Hasan; Shewokis, Patricia A; Izzetoğlu, Meltem; Çakır, Murat P; Onaral, Banu

    2012-01-01

    Recent neuroimaging studies have implicated prefrontal and parietal cortices for mathematical problem solving. Mental arithmetic tasks have been used extensively to study neural correlates of mathematical reasoning. In the present study we used geometric problem sets (tangram tasks) that require executive planning and visuospatial reasoning without any linguistic representation interference. We used portable optical brain imaging (functional near infrared spectroscopy--fNIR) to monitor hemodynamic changes within anterior prefrontal cortex during tangram tasks. Twelve healthy subjects were asked to solve a series of computerized tangram puzzles and control tasks that required same geometric shape manipulation without problem solving. Total hemoglobin (HbT) concentration changes indicated a significant increase during tangram problem solving in the right hemisphere. Moreover, HbT changes during failed trials (when no solution found) were significantly higher compared to successful trials. These preliminary results suggest that fNIR can be used to assess cortical activation changes induced by geometric problem solving. Since fNIR is safe, wearable and can be used in ecologically valid environments such as classrooms, this neuroimaging tool may help to improve and optimize learning in educational settings.

  8. Inequality signals in dorsolateral prefrontal cortex inform social preference models.

    Science.gov (United States)

    Holper, Lisa; Burke, Christopher J; Fausch, Christoph; Seifritz, Erich; Tobler, Philippe N

    2018-05-01

    Humans typically display inequality aversion in social situations, which manifests itself as a preference for fairer distributions of resources. However, people differ in the degree to which they dislike being worse off [disadvantageous inequality (DI) aversion] or better off [advantageous inequality (AI) aversion] than others. Competing models explain such behavior by focusing on aversion to payoff differences, maximization of total payoff or reciprocity. Using functional near-infrared spectroscopy, we asked which of these theories could better explain dorsolateral prefrontal cortex (dlPFC) activity while participants accepted or punished fair vs unfair monetary transfers in an anonymous norm compliance task. We found that while all participants exhibited DI aversion, there were substantial differences in preferences for AI, which were strongly predicted by dlPFC activation. Model comparisons revealed that both punishment behavior and prefrontal activity were best explained by a model that allowed for AI seeking rather than imposing aversion. Moreover, enhancing this model by taking into account behavioral response times, as a proxy for choice difficulty, further improved model fits. Our data provide evidence that the dlPFC encodes subjective values of payoff inequality and that this representation is richer than envisaged by standard models of social preferences.

  9. Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

    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

  11. Levels of integration in cognitive control and sequence processing in the prefrontal cortex.

    Science.gov (United States)

    Bahlmann, Jörg; Korb, Franziska M; Gratton, Caterina; Friederici, Angela D

    2012-01-01

    Cognitive control is necessary to flexibly act in changing environments. Sequence processing is needed in language comprehension to build the syntactic structure in sentences. Functional imaging studies suggest that sequence processing engages the left ventrolateral prefrontal cortex (PFC). In contrast, cognitive control processes additionally recruit bilateral rostral lateral PFC regions. The present study aimed to investigate these two types of processes in one experimental paradigm. Sequence processing was manipulated using two different sequencing rules varying in complexity. Cognitive control was varied with different cue-sets that determined the choice of a sequencing rule. Univariate analyses revealed distinct PFC regions for the two types of processing (i.e. sequence processing: left ventrolateral PFC and cognitive control processing: bilateral dorsolateral and rostral PFC). Moreover, in a common brain network (including left lateral PFC and intraparietal sulcus) no interaction between sequence and cognitive control processing was observed. In contrast, a multivariate pattern analysis revealed an interaction of sequence and cognitive control processing, such that voxels in left lateral PFC and parietal cortex showed different tuning functions for tasks involving different sequencing and cognitive control demands. These results suggest that the difference between the process of rule selection (i.e. cognitive control) and the process of rule-based sequencing (i.e. sequence processing) find their neuronal underpinnings in distinct activation patterns in lateral PFC. Moreover, the combination of rule selection and rule sequencing can shape the response of neurons in lateral PFC and parietal cortex.

  12. The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination.

    Science.gov (United States)

    Mair, Robert G; Miller, Rikki L A; Wormwood, Benjamin A; Francoeur, Miranda J; Onos, Kristen D; Gibson, Brett M

    2015-07-01

    Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

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    Hiroshi Ueno

    2015-01-01

    Full Text Available Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28 or P58 on the density of parvalbumin (PV, calbindin (CB, and calretinin (CR neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6. Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  14. Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training.

    Science.gov (United States)

    Wass, Christopher; Pizzo, Alessandro; Sauce, Bruno; Kawasumi, Yushi; Sturzoiu, Tudor; Ree, Fred; Otto, Tim; Matzel, Louis D

    2013-10-15

    A common source of variance (i.e., "general intelligence") underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to co-vary with general intelligence, and dopamine D1 signaling in prefrontal cortex can modulate attentional abilities. Based on their aggregate performance across five diverse tests of learning, here we characterized the general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum. Increased activation of D1R-containing neurons in the prelimbic cortex (but not the agranular insular cortex or dorsomedial striatum) was observed in animals of high GCA relative to those of low GCA (quantified by c-Fos activation in response to the D1 agonist). However, a Western blot analysis revealed no differences in the density of D1Rs in the prelimbic cortex between animals of high and low GCA. Last, it was observed that working memory training promoted an increase in animals' GCA and enhanced D1R-mediated neuronal activation in the prelimbic cortex. These results suggest that the sensitivity (but not density) of D1Rs in the prelimbic cortex may both regulate GCA and be a target for working memory training.

  15. Lateral prefrontal cortex subregions make dissociable contributions during fluid reasoning.

    Science.gov (United States)

    Hampshire, Adam; Thompson, Russell; Duncan, John; Owen, Adrian M

    2011-01-01

    Reasoning is a key component of adaptable "executive" behavior and is known to depend on a network of frontal and parietal brain regions. However, the mechanisms by which this network supports reasoning and adaptable behavior remain poorly defined. Here, we examine the relationship between reasoning, executive control, and frontoparietal function in a series of nonverbal reasoning experiments. Our results demonstrate that, in accordance with previous studies, a network of frontal and parietal brain regions is recruited during reasoning. Our results also reveal that this network can be fractionated according to how different subregions respond when distinct reasoning demands are manipulated. While increased rule complexity modulates activity within a right lateralized network including the middle frontal gyrus and the superior parietal cortex, analogical reasoning demand-or the requirement to remap rules on to novel features-recruits the left inferior rostrolateral prefrontal cortex and the lateral occipital complex. In contrast, the posterior extent of the inferior frontal gyrus, associated with simpler executive demands, is not differentially sensitive to rule complexity or analogical demand. These findings accord well with the hypothesis that different reasoning demands are supported by different frontal and parietal subregions.

  16. Lateral Prefrontal Cortex Subregions Make Dissociable Contributions during Fluid Reasoning

    Science.gov (United States)

    Thompson, Russell; Duncan, John; Owen, Adrian M.

    2011-01-01

    Reasoning is a key component of adaptable “executive” behavior and is known to depend on a network of frontal and parietal brain regions. However, the mechanisms by which this network supports reasoning and adaptable behavior remain poorly defined. Here, we examine the relationship between reasoning, executive control, and frontoparietal function in a series of nonverbal reasoning experiments. Our results demonstrate that, in accordance with previous studies, a network of frontal and parietal brain regions is recruited during reasoning. Our results also reveal that this network can be fractionated according to how different subregions respond when distinct reasoning demands are manipulated. While increased rule complexity modulates activity within a right lateralized network including the middle frontal gyrus and the superior parietal cortex, analogical reasoning demand—or the requirement to remap rules on to novel features—recruits the left inferior rostrolateral prefrontal cortex and the lateral occipital complex. In contrast, the posterior extent of the inferior frontal gyrus, associated with simpler executive demands, is not differentially sensitive to rule complexity or analogical demand. These findings accord well with the hypothesis that different reasoning demands are supported by different frontal and parietal subregions. PMID:20483908

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

    Science.gov (United States)

    Richard, Jocelyn M; Berridge, Kent C

    2013-02-15

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

  18. A General Role for Medial Prefrontal Cortex in Event Prediction

    Science.gov (United States)

    2014-07-11

    al., 2001; Nee and Brown, 2013; Mian et al., 2014) and known to project reciprocally to mPFC (Barbas and Pandya, 1989). Another possible substrate of...A. J., and Li , C. R. (2013). Bayesian prediction and evaluation in the anterior cingulate cortex. J. Neurosci. 33, 2039–2047. doi: 10. 1523/JNEUROSCI...prediction in mPFC Mian , M. K., Sheth, S. A., Patel, S. R., Spiliopoulos, K., Eskandar, E. N., and Williams, Z. M. (2014). Encoding of rules by neurons in the

  19. Segregation of the human medial prefrontal cortex in social cognition

    Directory of Open Access Journals (Sweden)

    Danilo eBzdok

    2013-05-01

    Full Text Available While the human medial prefrontal cortex (mPFC is widely believed to be a key node of neural networks relevant for socio-emotional processing, its functional subspecialization is still poorly understood. We thus revisited the often assumed differentiation of the mPFC in social cognition along its ventral-dorsal axis. Our neuroinformatic analysis was based on a neuroimaging meta-analysis of perspective-taking that yielded two separate clusters in the ventral and dorsal mPFC, respectively. We determined each seed region’s brain-wide interaction pattern by two complementary measures of functional connectivity: co-activation across a wide range of neuroimaging studies archived in the BrainMap database and correlated signal fluctuations during unconstrained (resting cognition. Furthermore, we characterized the functions associated with these two regions using the BrainMap database. Across methods, the ventral mPFC was more strongly connected with the nucleus accumbens, hippocampus, posterior cingulate cortex, and retrosplenial cortex, while the dorsal mPFC was more strongly connected with the inferior frontal gyrus, temporo-parietal junction, and middle temporal gyrus. Further, the ventral mPFC was selectively associated with action execution, olfaction, and reward related tasks, while the dorsal mPFC was selectively associated with perspective-taking and episodic memory retrieval. The ventral mPFC is therefore predominantly involved in sensory-driven, approach/avoidance-modulating, and evaluation-related processing, whereas the dorsal mPFC is predominantly involved in internally driven, memory-informed, and metacognition-related processing in social cognition.

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

    Science.gov (United States)

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

    2013-05-01

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

  1. Layer-specific high-frequency spiking in the prefrontal cortex of awake rats

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    Zimbo Saroeni Raymond Maria Boudewijns

    2013-06-01

    Full Text Available Cortical pyramidal neurons show irregular in vivo action potential (AP spiking with high frequency bursts occurring on sparse background activity. Somatic APs can backpropagate from soma into basal and apical dendrites and locally generate dendritic calcium spikes. The critical AP frequency for generation of such dendritic calcium spikes can be very different depending on cell-type or brain area involved. Previously, it was shown in vitro that calcium electrogenesis can also be induced in L(ayer 5 pyramidal neurons of prefrontal cortex (PFC. It remains an open question whether somatic burst spiking and resulting dendritic calcium electrogenesis also occur in morphologically more compact L2/3 pyramidal neurons. Furthermore, it is not known whether critical frequencies that trigger dendritic calcium electrogenesis occur in PFC under awake conditions in vivo. Here, we addressed these issues and found that pyramidal neurons in both PFC L2/3 and L5 in awake rats spike APs in short bursts, but with different probabilities. The critical frequency for calcium electrogenesis in vitro was layer-specific and lower in L5 neurons compared to L2/3. Taking the in vitro critical frequency as predictive measure for dendritic electrogenesis during in vivo spontaneous activity, supracritical bursts in vivo were observed in a larger fraction of L5 neurons compared to L2/3 neurons but with similar incidence within these subpopulations. Together, these results show that in PFC of awake rats, AP spiking occurs at frequencies that are relevant for dendritic calcium electrogenesis and suggest that in awake rat PFC, dendritic calcium electrogenesis may be involved in neuronal computation.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  3. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    Science.gov (United States)

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Prefrontal cortex glutamate correlates with mental perspective-taking.

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    Christiane Montag

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

  5. Reward-dependent modulation of working memory in lateral prefrontal cortex.

    Science.gov (United States)

    Kennerley, Steven W; Wallis, Jonathan D

    2009-03-11

    Although research implicates lateral prefrontal cortex (PFC) in executive control and goal-directed behavior, it remains unclear how goals influence executive processes. One possibility is that goal-relevant information, such as expected rewards, could modulate the representation of information relating to executive control, thereby ensuring the efficient allocation of cognitive resources. To investigate this, we examined how reward modulated spatial working memory. Past studies investigating spatial working memory have focused on dorsolateral PFC, but this area only weakly connects with areas processing reward. Ventrolateral PFC has better connections in this regard. Thus, we contrasted the functional properties of single neurons in ventrolateral and dorsolateral PFC as two subjects performed a task that required them to hold spatial information in working memory under different expectancies of reward for correct performance. We balanced the order of presentation of spatial and reward information so we could assess the neuronal encoding of the two pieces of information independently and conjointly. Neurons in ventrolateral PFC encoded both spatial and reward information earlier, stronger and in a more sustained manner than neurons in dorsolateral PFC. Within ventrolateral PFC, spatial selectivity was more prevalent on the inferior convexity than within the principal sulcus. Finally, when reward increased spatial selectivity, behavioral performance improved, whereas when reward decreased spatial selectivity, behavioral performance deteriorated. These results suggest that ventrolateral PFC may be a locus whereby information about expected rewards can modulate information in working memory. The pattern of results is consistent with a role for ventrolateral PFC in attentional control.

  6. Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

    Science.gov (United States)

    Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

    2015-08-01

    Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P curcumin had a protective role against the changes in the rats.

  7. Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats

    NARCIS (Netherlands)

    Yamada, Makiko; Kawahara, Yukie; Kaneko, Fumi; Kishikawa, Yuki; Sotogaku, Naoki; Poppinga, Wilfred J.; Folgering, Joost H. A.; Dremencov, Eliyahu; Kawahara, Hiroshi; Nishi, Akinori

    Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC

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

    Science.gov (United States)

    Viswanathan, Pooja; Nieder, Andreas

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Gregory R Rompala

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

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  12. Chronic stress from adolescence to aging in the prefrontal cortex: A neuroimmune perspective.

    Science.gov (United States)

    Macht, Victoria A; Reagan, Lawrence P

    2018-04-01

    The development of the organism is a critical variable which influences the magnitude, duration, and reversibility of the effects of chronic stress. Such factors are relevant to the prefrontal cortex (PFC), as this brain region is the last to mature, the first to decline, and is highly stress-sensitive. Therefore, this review will examine the intersection between the nervous system and immune system at glutamatergic synapses in the PFC across three developmental periods: adolescence, adulthood, and aging. Glutamatergic synapses are tightly juxtaposed with microglia and astrocytes, and each of these cell types exhibits their own developmental trajectory. Not only does chronic stress differentially impact each of these cell types across development, but chronic stress also alters intercellular communication within this quad-partite synapse. These observations suggest that developmental shifts in both neural and immune function across neurons, microglia, and astrocytes mediate shifting effects of chronic stress on glutamatergic transmission. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    Science.gov (United States)

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  14. A hierarchy for relational reasoning in the prefrontal cortex.

    Science.gov (United States)

    Krawczyk, Daniel C; Michelle McClelland, M; Donovan, Colin M

    2011-05-01

    The human brain possesses a unique capacity to reason about abstract relationships among items in our environment. The neural organization of reasoning abilities has remained elusive. Two approaches toward investigating human reasoning have involved studying visuo-spatial reasoning abilities and studying analogical reasoning. These approaches have both revealed anterior prefrontal cortex (PFC) involvement, but no prior studies have jointly investigated these two forms of reasoning to understand any potential convergence of activation within the PFC. Using fMRI, we tested the extent to which these two forms of reasoning (visuo-spatial and analogical) overlap in PFC activation. We conducted a visuo-spatial reasoning task that required processing multiple changes across three abstract pictures. This task activated a progressively anterior series of PFC regions when multiple relations had to be integrated. We also conducted a four-term analogy task in a stage-wise manner and compared results from this task to semantic and perceptual control conditions that did not require integrating relations across the problems. We found greater activation for analogical reasoning in the series of PFC regions that were sequentially involved in the visuo-spatial reasoning task. These findings indicate that stages of neural processing overlap for different domains within human reasoning. The pattern of differences across the analogy task suggests a hierarchical organization for relational reasoning across domains in which posterior frontal cortex is active across concrete reasoning tasks, while progressively more anterior regions are recruited to process increasingly abstract representations in reasoning. Copyright © 2010 Elsevier Srl. All rights reserved.

  15. Emotion and the prefrontal cortex: An integrative review.

    Science.gov (United States)

    Dixon, Matthew L; Thiruchselvam, Ravi; Todd, Rebecca; Christoff, Kalina

    2017-10-01

    The prefrontal cortex (PFC) plays a critical role in the generation and regulation of emotion. However, we lack an integrative framework for understanding how different emotion-related functions are organized across the entire expanse of the PFC, as prior reviews have generally focused on specific emotional processes (e.g., decision making) or specific anatomical regions (e.g., orbitofrontal cortex). Additionally, psychological theories and neuroscientific investigations have proceeded largely independently because of the lack of a common framework. Here, we provide a comprehensive review of functional neuroimaging, electrophysiological, lesion, and structural connectivity studies on the emotion-related functions of 8 subregions spanning the entire PFC. We introduce the appraisal-by-content model, which provides a new framework for integrating the diverse range of empirical findings. Within this framework, appraisal serves as a unifying principle for understanding the PFC's role in emotion, while relative content-specialization serves as a differentiating principle for understanding the role of each subregion. A synthesis of data from affective, social, and cognitive neuroscience studies suggests that different PFC subregions are preferentially involved in assigning value to specific types of inputs: exteroceptive sensations, episodic memories and imagined future events, viscero-sensory signals, viscero-motor signals, actions, others' mental states (e.g., intentions), self-related information, and ongoing emotions. We discuss the implications of this integrative framework for understanding emotion regulation, value-based decision making, emotional salience, and refining theoretical models of emotion. This framework provides a unified understanding of how emotional processes are organized across PFC subregions and generates new hypotheses about the mechanisms underlying adaptive and maladaptive emotional functioning. (PsycINFO Database Record (c) 2017 APA, all

  16. Disrupting the right prefrontal cortex alters moral judgement.

    Science.gov (United States)

    Tassy, Sébastien; Oullier, Olivier; Duclos, Yann; Coulon, Olivier; Mancini, Julien; Deruelle, Christine; Attarian, Sharam; Felician, Olivier; Wicker, Bruno

    2012-03-01

    Humans daily face social situations involving conflicts between competing moral decision. Despite a substantial amount of studies published over the past 10 years, the respective role of emotions and reason, their possible interaction, and their behavioural expression during moral evaluation remains an unresolved issue. A dualistic approach to moral evaluation proposes that the right dorsolateral prefrontal cortex (rDLPFc) controls emotional impulses. However, recent findings raise the possibility that the right DLPFc processes emotional information during moral decision making. We used repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt rDLPFc activity before measuring decision making in the context of moral dilemmas. Results reveal an increase of the probability of utilitarian responses during objective evaluation of moral dilemmas in the rTMS group (compared to a SHAM one). This suggests that the right DLPFc function not only participates to a rational cognitive control process, but also integrates emotions generated by contextual information appraisal, which are decisive for response selection in moral judgements. © The Author (2011). Published by Oxford University Press.

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

    Science.gov (United States)

    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. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Specialization of the Rostral Prefrontal Cortex for Distinct Analogy Processes

    Science.gov (United States)

    Gilbert, Sam J.; Benoit, Roland G.; Burgess, Paul W.

    2010-01-01

    Analogical reasoning is central to learning and abstract thinking. It involves using a more familiar situation (source) to make inferences about a less familiar situation (target). According to the predominant cognitive models, analogical reasoning includes 1) generation of structured mental representations and 2) mapping based on structural similarities between them. This study used functional magnetic resonance imaging to specify the role of rostral prefrontal cortex (PFC) in these distinct processes. An experimental paradigm was designed that enabled differentiation between these processes, by temporal separation of the presentation of the source and the target. Within rostral PFC, a lateral subregion was activated by analogy task both during study of the source (before the source could be compared with a target) and when the target appeared. This may suggest that this subregion supports fundamental analogy processes such as generating structured representations of stimuli but is not specific to one particular processing stage. By contrast, a dorsomedial subregion of rostral PFC showed an interaction between task (analogy vs. control) and period (more activated when the target appeared). We propose that this region is involved in comparison or mapping processes. These results add to the growing evidence for functional differentiation between rostral PFC subregions. PMID:20156841

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Anterior medial prefrontal cortex implements social priming of mimicry.

    Science.gov (United States)

    Wang, Yin; Hamilton, Antonia F de C

    2015-04-01

    The neural and cognitive mechanisms by which primed constructs can impact on social behavior are poorly understood. In the present study, we used functional magnetic resonance imaging (fMRI) to explore how scrambled sentence priming can impact on mimicry behavior. Sentences involving pro/antisocial events from a first/third-person point of view were presented in short blocks, followed by a reaction-time assessment of mimicry. Behavioral results showed that both prosociality and viewpoint impact on mimicry, and fMRI analysis showed this effect is implemented by anterior medial prefrontal cortex (amPFC). We suggest that social primes may subtly modulate processing in amPFC in a manner linked to the later behavior, and that this same region also implements the top-down control of mimicry responses. This priming may be linked to processing of self-schemas in amPFC. Our findings demonstrate how social priming can be studied with fMRI, and have important implications for our understanding of the underlying mechanisms of prime-to-behavior effects as well as for current theories in social psychology. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine

    NARCIS (Netherlands)

    Poorthuis, R.B.; Bloem, B.R.; Verhoog, M.B.; Mansvelder, H.D.

    2013-01-01

    Adolescence is a period in which the developing prefrontal cortex (PFC) is sensitive to maladaptive changes when exposed to nicotine. Nicotine affects PFC function and repeated exposure to nicotine during adolescence impairs attention performance and impulse control during adulthood. Nicotine

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

    Science.gov (United States)

    Pergolizzi, Denise; Chua, Elizabeth F.

    2016-01-01

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

  4. Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex.

    Science.gov (United States)

    Ruan, Hongyu; Yao, Wei-Dong

    2017-01-25

    Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP). After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons is induced at +30 ms, a normally ineffective timing interval for t-LTP induction in saline-exposed mice. This cocaine-induced, extended-timing t-LTP lasts for ∼1 week after terminating cocaine and is accompanied by an increased susceptibility to potentiation by fewer pre-post spike pairs, indicating a reduced t-LTP induction threshold. Basal synaptic strength and the maximal attainable t-LTP magnitude remain unchanged after cocaine exposure. We further show that the cocaine facilitation of t-LTP induction is caused by sensitized D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons, which then pathologically recruits voltage-gated l-type Ca 2+ channels that synergize with GluN2A-containing NMDA receptors to drive t-LTP at extended timing. Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifies the coincidence detection window during Hebbian plasticity to facilitate associative synaptic potentiation in prefrontal excitatory circuits. By modifying rules that govern activity-dependent synaptic plasticity, addictive drugs can derail the experience-driven neural circuit remodeling process important for executive control of reward and addiction. It is believed that addictive drugs often render an addict's brain reward system hypersensitive, leaving the individual more susceptible to

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

    Science.gov (United States)

    Csabai, Dávid; Wiborg, Ove; Czéh, Boldizsár

    2018-01-01

    Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I) and symmetric (Type II) synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network connectivity is likely

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

    Directory of Open Access Journals (Sweden)

    Dávid Csabai

    2018-01-01

    Full Text Available Stressful experiences can induce structural changes in neurons of the limbic system. These cellular changes contribute to the development of stress-induced psychopathologies like depressive disorders. In the prefrontal cortex of chronically stressed animals, reduced dendritic length and spine loss have been reported. This loss of dendritic material should consequently result in synapse loss as well, because of the reduced dendritic surface. But so far, no one studied synapse numbers in the prefrontal cortex of chronically stressed animals. Here, we examined synaptic contacts in rats subjected to an animal model for depression, where animals are exposed to a chronic stress protocol. Our hypothesis was that long term stress should reduce the number of axo-spinous synapses in the medial prefrontal cortex. Adult male rats were exposed to daily stress for 9 weeks and afterward we did a post mortem quantitative electron microscopic analysis to quantify the number and morphology of synapses in the infralimbic cortex. We analyzed asymmetric (Type I and symmetric (Type II synapses in all cortical layers in control and stressed rats. We also quantified axon numbers and measured the volume of the infralimbic cortex. In our systematic unbiased analysis, we examined 21,000 axon terminals in total. We found the following numbers in the infralimbic cortex of control rats: 1.15 × 109 asymmetric synapses, 1.06 × 108 symmetric synapses and 1.00 × 108 myelinated axons. The density of asymmetric synapses was 5.5/μm3 and the density of symmetric synapses was 0.5/μm3. Average synapse membrane length was 207 nm and the average axon terminal membrane length was 489 nm. Stress reduced the number of synapses and myelinated axons in the deeper cortical layers, while synapse membrane lengths were increased. These stress-induced ultrastructural changes indicate that neurons of the infralimbic cortex have reduced cortical network connectivity. Such reduced network

  7. Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

    Science.gov (United States)

    Wang, Minghui; Perova, Zinaida; Arenkiel, Benjamin R.

    2014-01-01

    When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression. PMID:24872553

  8. Neural correlates of auditory recognition memory in primate lateral prefrontal cortex.

    Science.gov (United States)

    Plakke, B; Ng, C-W; Poremba, A

    2013-08-06

    The neural underpinnings of working and recognition memory have traditionally been studied in the visual domain and these studies pinpoint the lateral prefrontal cortex (lPFC) as a primary region for visual memory processing (Miller et al., 1996; Ranganath et al., 2004; Kennerley and Wallis, 2009). Herein, we utilize single-unit recordings for the same region in monkeys (Macaca mulatta) but investigate a second modality examining auditory working and recognition memory during delayed matching-to-sample (DMS) performance. A large portion of neurons in the dorsal and ventral banks of the principal sulcus (area 46, 46/9) show DMS event-related activity to one or more of the following task events: auditory cues, memory delay, decision wait time, response, and/or reward portions. Approximately 50% of the neurons show evidence of auditory-evoked activity during the task and population activity demonstrated encoding of recognition memory in the form of match enhancement. However, neither robust nor sustained delay activity was observed. The neuronal responses during the auditory DMS task are similar in many respects to those found within the visual working memory domain, which supports the hypothesis that the lPFC, particularly area 46, functionally represents key pieces of information for recognition memory inclusive of decision-making, but regardless of modality. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia.

    Science.gov (United States)

    Chen, Yi-Wen; Wable, Gauri Satish; Chowdhury, Tara Gunkali; Aoki, Chiye

    2016-06-01

    Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neurons (L5P) in the prefrontal cortex. Contact lengths were, on average, 40% greater for the ABA-induced mice, relative to controls. Correspondingly, the proportion of L5P perikaryal plasma membrane contacted by GABAergic terminals was 45% greater for the ABA mice. Contact lengths in the anterior cingulate cortex correlated negatively and strongly with the overall wheel activity after FR (R = -0.87, P resilience through suppression of wheel running, a behavior that is intrinsically rewarding and helpful for foraging but maladaptive within a cage. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    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.

  11. GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia.

    Directory of Open Access Journals (Sweden)

    Hsien-Sung Huang

    2007-08-01

    Full Text Available Dysfunction of prefrontal cortex in schizophrenia includes changes in GABAergic mRNAs, including decreased expression of GAD1, encoding the 67 kDa glutamate decarboxylase (GAD67 GABA synthesis enzyme. The underlying molecular mechanisms remain unclear. Alterations in DNA methylation as an epigenetic regulator of gene expression are thought to play a role but this hypothesis is difficult to test because no techniques are available to extract DNA from GAD1 expressing neurons efficiently from human postmortem brain. Here, we present an alternative approach that is based on immunoprecipitation of mononucleosomes with anti-methyl-histone antibodies differentiating between sites of potential gene expression as opposed to repressive or silenced chromatin. Methylation patterns of CpG dinucleotides at the GAD1 proximal promoter and intron 2 were determined for each of the two chromatin fractions separately, using a case-control design for 14 schizophrenia subjects affected by a decrease in prefrontal GAD1 mRNA levels. In controls, the methylation frequencies at CpG dinucleotides, while overall higher in repressive as compared to open chromatin, did not exceed 5% at the proximal GAD1 promoter and 30% within intron 2. Subjects with schizophrenia showed a significant, on average 8-fold deficit in repressive chromatin-associated DNA methylation at the promoter. These results suggest that chromatin remodeling mechanisms are involved in dysregulated GABAergic gene expression in schizophrenia.

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

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    Anne eGuhn

    2014-02-01

    Full Text Available The extinction of conditioned fear is dependent on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC. In rats, high-frequency electrical mPFC stimulation was shown to improve extinction by 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 two-day fear conditioning and extinction paradigm. rTMS 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 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 which can be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy.

  13. Context-Dependent Modulation of Functional Connectivity: Secondary Somatosensory Cortex to Prefrontal Cortex Connections in Two-Stimulus-Interval Discrimination Tasks

    OpenAIRE

    Chow, Stephanie S.; Romo, Ranulfo; Brody, Carlos D.

    2009-01-01

    In a complex world, a sensory cue may prompt different actions in different contexts. A laboratory example of context-dependent sensory processing is the two-stimulus-interval discrimination task. In each trial, a first stimulus (f1) must be stored in short-term memory and later compared with a second stimulus (f2), for the animal to come to a binary decision. Prefrontal cortex (PFC) neurons need to interpret the f1 information in one way (perhaps with a positive weight) and the f2 informatio...

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

    Science.gov (United States)

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

    2014-11-01

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

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

    DEFF Research Database (Denmark)

    Rinaldi, Tania; Perrodin, Catherine; Markram, Henry

    2008-01-01

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

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

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    Shintaro eFunahashi

    2015-02-01

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

  17. Implicit and Explicit Learning Mechanisms Meet in Monkey Prefrontal Cortex.

    Science.gov (United States)

    Chafee, Matthew V; Crowe, David A

    2017-10-11

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

  18. Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex.

    Science.gov (United States)

    Ruiz-Mejias, Marcel; Martinez de Lagran, Maria; Mattia, Maurizio; Castano-Prat, Patricia; Perez-Mendez, Lorena; Ciria-Suarez, Laura; Gener, Thomas; Sancristobal, Belen; García-Ojalvo, Jordi; Gruart, Agnès; Delgado-García, José M; Sanchez-Vives, Maria V; Dierssen, Mara

    2016-03-30

    The dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A is a serine/threonine kinase involved in neuronal differentiation and synaptic plasticity and a major candidate of Down syndrome brain alterations and cognitive deficits. DYRK1A is strongly expressed in the cerebral cortex, and its overexpression leads to defective cortical pyramidal cell morphology, synaptic plasticity deficits, and altered excitation/inhibition balance. These previous observations, however, do not allow predicting how the behavior of the prefrontal cortex (PFC) network and the resulting properties of its emergent activity are affected. Here, we integrate functional, anatomical, and computational data describing the prefrontal network alterations in transgenic mice overexpressingDyrk1A(TgDyrk1A). Usingin vivoextracellular recordings, we show decreased firing rate and gamma frequency power in the prefrontal network of anesthetized and awakeTgDyrk1Amice. Immunohistochemical analysis identified a selective reduction of vesicular GABA transporter punctae on parvalbumin positive neurons, without changes in the number of cortical GABAergic neurons in the PFC ofTgDyrk1Amice, which suggests that selective disinhibition of parvalbumin interneurons would result in an overinhibited functional network. Using a conductance-based computational model, we quantitatively demonstrate that this alteration could explain the observed functional deficits including decreased gamma power and firing rate. Our results suggest that dysfunction of cortical fast-spiking interneurons might be central to the pathophysiology of Down syndrome. DYRK1Ais a major candidate gene in Down syndrome. Its overexpression results into altered cognitive abilities, explained by defective cortical microarchitecture and excitation/inhibition imbalance. An open question is how these deficits impact the functionality of the prefrontal cortex network. Combining functional, anatomical, and computational approaches, we identified

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

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    Abdul-Rahman Omar

    2012-02-01

    Full Text Available Abstract 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.

  20. Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex

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    Kuswati

    2015-04-01

    Full Text Available Background Stress is one of the factors that cause apoptosis in neuronal cells. Centella asiatica has a neuroprotective effect that can inhibit apoptosis. This study aimed to examine the effect of Centella asiatica ethanol extract on B-cell lymphoma 2 (Bcl-2 protein expression in the prefrontal cortex of rats. Methods An experimental study was conducted on 34 brain tissue samples from male Sprague Dawley rats exposed to chronic restraint stress for 21 days. The samples were taken from following groups: non-stress group K, negative control group P1 (stress + arabic gum powder, P2 (stress + C.asiatica at 150 mg/kgBW, P3 (stress + C.asiatica at 300 mg/kg BW, P4 (stress + C.asiatica at 600 mg/kg body weight and positive control group P5 (stress + fluoxetine at 10 mg/kgBW. The samples were made into sections that were stained immunohistochemically using Bcl-2 antibody to determine the percentage of cells expressing Bcl-2. Data were analyzed using one way ANOVA test followed by a post - hoc test. Results There were significant differences in mean Bcl-2 expression between the groups receiving Centella asiatica compared with the non-stress group and stress-only group (negative control group (p<0.05. The results were comparable to those of the fluoxetine treatment group. Conclusion The Centella asiatica ethanol extract was able to increase Bcl-2 expression in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress. This study suggests that Centella asiatica may be useful in the treatment of cerebral stress.

  1. Coordinated cell type-specific epigenetic remodeling in prefrontal cortex begins before birth and continues into early adulthood.

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    Hennady P Shulha

    2013-04-01

    Full Text Available Development of prefrontal and other higher-order association cortices is associated with widespread changes in the cortical transcriptome, particularly during the transitions from prenatal to postnatal development, and from early infancy to later stages of childhood and early adulthood. However, the timing and longitudinal trajectories of neuronal gene expression programs during these periods remain unclear in part because of confounding effects of concomitantly occurring shifts in neuron-to-glia ratios. Here, we used cell type-specific chromatin sorting techniques for genome-wide profiling of a histone mark associated with transcriptional regulation--H3 with trimethylated lysine 4 (H3K4me3--in neuronal chromatin from 31 subjects from the late gestational period to 80 years of age. H3K4me3 landscapes of prefrontal neurons were developmentally regulated at 1,157 loci, including 768 loci that were proximal to transcription start sites. Multiple algorithms consistently revealed that the overwhelming majority and perhaps all of developmentally regulated H3K4me3 peaks were on a unidirectional trajectory defined by either rapid gain or loss of histone methylation during the late prenatal period and the first year after birth, followed by similar changes but with progressively slower kinetics during early and later childhood and only minimal changes later in life. Developmentally downregulated H3K4me3 peaks in prefrontal neurons were enriched for Paired box (Pax and multiple Signal Transducer and Activator of Transcription (STAT motifs, which are known to promote glial differentiation. In contrast, H3K4me3 peaks subject to a progressive increase in maturing prefrontal neurons were enriched for activating protein-1 (AP-1 recognition elements that are commonly associated with activity-dependent regulation of neuronal gene expression. We uncovered a developmental program governing the remodeling of neuronal histone methylation landscapes in the prefrontal

  2. Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear.

    Science.gov (United States)

    Marek, Roger; Jin, Jingji; Goode, Travis D; Giustino, Thomas F; Wang, Qian; Acca, Gillian M; Holehonnur, Roopashri; Ploski, Jonathan E; Fitzgerald, Paul J; Lynagh, Timothy; Lynch, Joseph W; Maren, Stephen; Sah, Pankaj

    2018-03-01

    The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together, our findings describe a previously unknown circuit mechanism for the contextual control of fear, and indicate that vHPC-mediated inhibition of IL is an essential neural substrate for fear relapse.

  3. Egalitarian reward contingency in competitive games and primate prefrontal neuronal activity.

    Science.gov (United States)

    Hosokawa, Takayuki; Watanabe, Masataka

    2015-01-01

    How people work to obtain a reward depends on the context of the reward delivery, such as the presence/absence of competition and the contingency of reward delivery. Since resources are limited, winning a competition is critically important for organisms' obtaining a reward. People usually expect ordinary performance-reward contingency, with better performers obtaining better rewards. Unordinary reward contingency, such as egalitarianism (equal rewards/no-rewards to both good and poor performers), dampens people's motivation. We previously reported that monkeys were more motivated, and neurons in the lateral prefrontal cortex (LPFC) showed higher outcome-related activity in a competitive than in a noncompetitive game (Hosokawa and Watanabe, 2012). However, monkey's behavior and LPFC neuronal activity have not been examined in a competitive situation with an unordinary performance-reward contingency. Also, the fixed performance-reward contingency in the previous study did not allow us to examine effects of win/loss separately from those of reward/no-reward on prefrontal neuronal activity. Here, we employed the egalitarian competitive situation in which both the winner and loser, or neither of them, got a reward as well as the normal competitive situation in which only the winner got a reward. Monkey's behavioral performance greatly deteriorated in trials with the egalitarian outcome conditions. LPFC neurons showed activities that reflected the normal or egalitarian outcome condition while very few neurons coded win/loss independent of reward/no-reward. Importantly, we found neurons that showed reward-related activity in the normal, but not in the egalitarian outcome conditions, even though the same reward was given to the animal. These results indicate that LPFC may play an important role in monitoring the current reward contingency and integrating it with the performance outcome (win-loss) for better performing the competitive game, and thus for better survival.

  4. Functional coupling networks inferred from prefrontal cortex activity show experience-related effective plasticity

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    Gaia Tavoni

    2017-10-01

    Full Text Available Functional coupling networks are widely used to characterize collective patterns of activity in neural populations. Here, we ask whether functional couplings reflect the subtle changes, such as in physiological interactions, believed to take place during learning. We infer functional network models reproducing the spiking activity of simultaneously recorded neurons in prefrontal cortex (PFC of rats, during the performance of a cross-modal rule shift task (task epoch, and during preceding and following sleep epochs. A large-scale study of the 96 recorded sessions allows us to detect, in about 20% of sessions, effective plasticity between the sleep epochs. These coupling modifications are correlated with the coupling values in the task epoch, and are supported by a small subset of the recorded neurons, which we identify by means of an automatized procedure. These potentiated groups increase their coativation frequency in the spiking data between the two sleep epochs, and, hence, participate to putative experience-related cell assemblies. Study of the reactivation dynamics of the potentiated groups suggests a possible connection with behavioral learning. Reactivation is largely driven by hippocampal ripple events when the rule is not yet learned, and may be much more autonomous, and presumably sustained by the potentiated PFC network, when learning is consolidated. Cell assemblies coding for memories are widely believed to emerge through synaptic modification resulting from learning, yet their identification from activity is very arduous. We propose a functional-connectivity-based approach to identify experience-related cell assemblies from multielectrode recordings in vivo, and apply it to the prefrontal cortex activity of rats recorded during a task epoch and the preceding and following sleep epochs. We infer functional couplings between the recorded cells in each epoch. Comparisons of the functional coupling networks across the epochs allow us

  5. Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

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    Ruixue Song

    2017-01-01

    Full Text Available Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC. Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

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

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    Antonio Homero Lara

    2015-12-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2011-11-09

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

  11. Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

    Science.gov (United States)

    Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

    2008-02-01

    Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

  12. Lower expression of glutamic acid decarboxylase 67 in the prefrontal cortex in schizophrenia: contribution of altered regulation by Zif268.

    Science.gov (United States)

    Kimoto, Sohei; Bazmi, H Holly; Lewis, David A

    2014-09-01

    Cognitive deficits of schizophrenia may be due at least in part to lower expression of the 67-kDa isoform of glutamic acid decarboxylase (GAD67), a key enzyme for GABA synthesis, in the dorsolateral prefrontal cortex of individuals with schizophrenia. However, little is known about the molecular regulation of lower cortical GAD67 levels in schizophrenia. The GAD67 promoter region contains a conserved Zif268 binding site, and Zif268 activation is accompanied by increased GAD67 expression. Thus, altered expression of the immediate early gene Zif268 may contribute to lower levels of GAD67 mRNA in the dorsolateral prefrontal cortex in schizophrenia. The authors used polymerase chain reaction to quantify GAD67 and Zif268 mRNA levels in dorsolateral prefrontal cortex area 9 from 62 matched pairs of schizophrenia and healthy comparison subjects, and in situ hybridization to assess Zif268 expression at laminar and cellular levels of resolution. The effects of potentially confounding variables were assessed in human subjects, and the effects of antipsychotic treatments were tested in antipsychotic-exposed monkeys. The specificity of the Zif268 findings was assessed by quantifying mRNA levels for other immediate early genes. GAD67 and Zif268 mRNA levels were significantly lower and were positively correlated in the schizophrenia subjects. Both Zif268 mRNA-positive neuron density and Zif268 mRNA levels per neuron were significantly lower in the schizophrenia subjects. These findings were robust to the effects of the confounding variables examined and differed from other immediate early genes. Deficient Zif268 mRNA expression may contribute to lower cortical GAD67 levels in schizophrenia, suggesting a potential mechanistic basis for altered cortical GABA synthesis and impaired cognition in schizophrenia.

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

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    Fumi eKatsuki

    2012-05-01

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

  14. Neuronal Kmt2a/Mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory.

    Science.gov (United States)

    Jakovcevski, Mira; Ruan, Hongyu; Shen, Erica Y; Dincer, Aslihan; Javidfar, Behnam; Ma, Qi; Peter, Cyril J; Cheung, Iris; Mitchell, Amanda C; Jiang, Yan; Lin, Cong L; Pothula, Venu; Stewart, A Francis; Ernst, Patricia; Yao, Wei-Dong; Akbarian, Schahram

    2015-04-01

    Neuronal histone H3-lysine 4 methylation landscapes are defined by sharp peaks at gene promoters and other cis-regulatory sequences, but molecular and cellular phenotypes after neuron-specific deletion of H3K4 methyl-regulators remain largely unexplored. We report that neuronal ablation of the H3K4-specific methyltransferase, Kmt2a/Mixed-lineage leukemia 1 (Mll1), in mouse postnatal forebrain and adult prefrontal cortex (PFC) is associated with increased anxiety and robust cognitive deficits without locomotor dysfunction. In contrast, only mild behavioral phenotypes were observed after ablation of the Mll1 ortholog Kmt2b/Mll2 in PFC. Impaired working memory after Kmt2a/Mll1 ablation in PFC neurons was associated with loss of training-induced transient waves of Arc immediate early gene expression critical for synaptic plasticity. Medial prefrontal layer V pyramidal neurons, a major output relay of the cortex, demonstrated severely impaired synaptic facilitation and temporal summation, two forms of short-term plasticity essential for working memory. Chromatin immunoprecipitation followed by deep sequencing in Mll1-deficient cortical neurons revealed downregulated expression and loss of the transcriptional mark, trimethyl-H3K4, at <50 loci, including the homeodomain transcription factor Meis2. Small RNA-mediated Meis2 knockdown in PFC was associated with working memory defects similar to those elicited by Mll1 deletion. Therefore, mature prefrontal neurons critically depend on maintenance of Mll1-regulated H3K4 methylation at a subset of genes with an essential role in cognition and emotion. Copyright © 2015 the authors 0270-6474/15/355097-12$15.00/0.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  17. Memory-guided sensory comparisons in the prefrontal cortex: contribution of putative pyramidal cells and interneurons.

    Science.gov (United States)

    Hussar, Cory R; Pasternak, Tatiana

    2012-02-22

    Comparing two stimuli that occur at different times demands the coordination of bottom-up and top-down processes. It has been hypothesized that the dorsolateral prefrontal (PFC) cortex, the likely source of top-down cortical influences, plays a key role in such tasks, contributing to both maintenance and sensory comparisons. We examined this hypothesis by recording from the PFC of monkeys comparing directions of two moving stimuli, S1 and S2, separated by a memory delay. We determined the contribution of the two principal cell types to these processes by classifying neurons into broad-spiking (BS) putative pyramidal cells and narrow-spiking (NS) putative local interneurons. During the delay, BS cells were more likely to exhibit anticipatory modulation and represent the remembered direction. While this representation was transient, appearing at different times in different neurons, it weakened when direction was not task relevant, suggesting its utility. During S2, both putative cell types showed comparison-related activity modulations. These modulations were of two types, each carried by different neurons, which either preferred trials with stimuli moving in the same direction or trials with stimuli of different directions. These comparison effects were strongly correlated with choice, suggesting their role in circuitry underlying decision making. These results provide the first demonstration of distinct contributions made by principal cell types to memory-guided perceptual decisions. During sensory stimulation both cell types represent behaviorally relevant stimulus features contributing to comparison and decision-related activity. However in the absence of sensory stimulation, putative pyramidal cells dominated, carrying information about the elapsed time and the preceding direction.

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

    Science.gov (United States)

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

    2015-06-26

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

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

    Science.gov (United States)

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

    2017-10-01

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

  20. Anatomical segmentation of the human medial prefrontal cortex

    NARCIS (Netherlands)

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

    2017-01-01

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

  1. Context-dependent representation of response-outcome in monkey prefrontal neurons.

    Science.gov (United States)

    Tsujimoto, Satoshi; Sawaguchi, Toshiyuki

    2005-07-01

    For behaviour to be purposeful, it is important to monitor the preceding behavioural context, particularly for factors regarding stimulus, response and outcome. The dorsolateral prefrontal cortex (DLPFC) appears to play a major role in such a context-dependent, flexible behavioural control system, and this area is likely to have a neuronal mechanism for such retrospective coding, which associates response-outcome with the information and/or neural systems that guided the response. To address this hypothesis, we recorded neuronal activity from the DLPFC of monkeys performing memory- and sensory-guided saccade tasks, each of which had two conditions with reward contingencies. We found that post-response activity of a subset of DLPFC neurons was modulated by three factors relating to earlier events: the direction of the immediately preceding response, its outcome (reward or non-reward) and the information type (memory or sensory) that guided the response. Such neuronal coding should play a role in associating response-outcome with information and/or neural systems used to guide behaviour - that is, 'retrospective monitoring' of behavioural context and/or neural systems used for guiding behaviour - thereby contributing to context-dependent, flexible control of behaviours.

  2. Cell-Type Specific Development of the Hyperpolarization-Activated Current, Ih, in Prefrontal Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Sha-Sha Yang

    2018-05-01

    Full Text Available H-current, also known as hyperpolarization-activated current (Ih, is an inward current generated by the hyperpolarization-activated cyclic nucleotide-gated (HCN cation channels. Ih plays an essential role in regulating neuronal properties, synaptic integration and plasticity, and synchronous activity in the brain. As these biological factors change across development, the brain undergoes varying levels of vulnerability to disorders like schizophrenia that disrupt prefrontal cortex (PFC-dependent function. However, developmental changes in Ih in PFC neurons remains untested. Here, we examine Ih in pyramidal neurons vs. gamma-aminobutyric acid (GABAergic parvalbumin-expressing (PV+ interneurons in developing mouse PFC. Our findings show that the amplitudes of Ih in these cell types are identical during the juvenile period but differ at later time points. In pyramidal neurons, Ih amplitude significantly increases from juvenile to adolescence and follows a similar trend into adulthood. In contrast, the amplitude of Ih in PV+ interneurons decreases from juvenile to adolescence, and does not change from adolescence to adulthood. Moreover, the kinetics of HCN channels in pyramidal neurons is significantly slower than in PV+ interneurons, with a gradual decrease in pyramidal neurons and a gradual increase in PV+ cells across development. Our study reveals distinct developmental trajectories of Ih in pyramidal neurons and PV+ interneurons. The cell-type specific alteration of Ih during the critical period from juvenile to adolescence reflects the contribution of Ih to the maturation of the PFC and PFC-dependent function. These findings are essential for a better understanding of normal PFC function, and for elucidating Ih’s crucial role in the pathophysiology of neurodevelopmental disorders.

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

    Science.gov (United States)

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

    2016-10-01

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

  4. Localization of dysfunction in major depressive disorder: prefrontal cortex and amygdala.

    Science.gov (United States)

    Murray, Elisabeth A; Wise, Steven P; Drevets, Wayne C

    2011-06-15

    Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of "self" underlies the core disorder in MDD; the medial frontal cortex represents "self"; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD. Published by Elsevier Inc.

  5. Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task

    OpenAIRE

    Asinof, Samuel K.; Paine, Tracie A.

    2012-01-01

    Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known. Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of γ-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia. Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parv...

  6. Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Maximiliano Rapanelli

    Full Text Available Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC and the hippocampus (HIPP during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and

  7. Coordinated Expression of Phosphoinositide Metabolic Genes during Development and Aging of Human Dorsolateral Prefrontal Cortex.

    Directory of Open Access Journals (Sweden)

    Stanley I Rapoport

    Full Text Available Phosphoinositides, lipid-signaling molecules, participate in diverse brain processes within a wide metabolic cascade.Gene transcriptional networks coordinately regulate the phosphoinositide cascade during human brain Development and Aging.We used the public BrainCloud database for human dorsolateral prefrontal cortex to examine age-related expression levels of 49 phosphoinositide metabolic genes during Development (0 to 20+ years and Aging (21+ years.We identified three groups of partially overlapping genes in each of the two intervals, with similar intergroup correlations despite marked phenotypic differences between Aging and Development. In each interval, ITPKB, PLCD1, PIK3R3, ISYNA1, IMPA2, INPPL1, PI4KB, and AKT1 are in Group 1, PIK3CB, PTEN, PIK3CA, and IMPA1 in Group 2, and SACM1L, PI3KR4, INPP5A, SYNJ1, and PLCB1 in Group 3. Ten of the genes change expression nonlinearly during Development, suggesting involvement in rapidly changing neuronal, glial and myelination events. Correlated transcription for some gene pairs likely is facilitated by colocalization on the same chromosome band.Stable coordinated gene transcriptional networks regulate brain phosphoinositide metabolic pathways during human Development and Aging.

  8. Theta–gamma coordination between anterior cingulate and prefrontal cortex indexes correct attention shifts

    Science.gov (United States)

    Voloh, Benjamin; Valiante, Taufik A.; Everling, Stefan; Womelsdorf, Thilo

    2015-01-01

    Anterior cingulate and lateral prefrontal cortex (ACC/PFC) are believed to coordinate activity to flexibly prioritize the processing of goal-relevant over irrelevant information. This between-area coordination may be realized by common low-frequency excitability changes synchronizing segregated high-frequency activations. We tested this coordination hypothesis by recording in macaque ACC/PFC during the covert utilization of attention cues. We found robust increases of 5–10 Hz (theta) to 35–55 Hz (gamma) phase–amplitude correlation between ACC and PFC during successful attention shifts but not before errors. Cortical sites providing theta phases (i) showed a prominent cue-induced phase reset, (ii) were more likely in ACC than PFC, and (iii) hosted neurons with burst firing events that synchronized to distant gamma activity. These findings suggest that interareal theta–gamma correlations could follow mechanistically from a cue-triggered reactivation of rule memory that synchronizes theta across ACC/PFC. PMID:26100868

  9. Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.

    Science.gov (United States)

    Toriumi, Kazuya; Oki, Mika; Muto, Eriko; Tanaka, Junko; Mouri, Akihiro; Mamiya, Takayoshi; Kim, Hyoung-Chun; Nabeshima, Toshitaka

    2016-06-01

    We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.

  10. Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

    Science.gov (United States)

    Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

    2016-12-01

    Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. What is the functional relevance of prefrontal cortex entrainment to hippocampal theta rhythms?

    Directory of Open Access Journals (Sweden)

    James Michael Hyman

    2011-03-01

    Full Text Available There has been considerable interest in the importance of oscillations in the brain and in how these oscillations relate to the firing of single neurons. Recently a number of studies have shown that the spiking of individual neurons in the medial prefrontal cortex (mPFC become entrained to the hippocampal (HPC theta rhythm. We recently showed that theta-entrained mPFC cells lost theta-entrainment specifically on error trials even though the firing rates of these cells did not change (Hyman et al., 2010. This implied that the level of HPC theta-entrainment of mPFC units was more predictive of trial outcome than differences in firing rates and that there is more information encoded by the mPFC on working memory tasks than can be accounted for by a simple rate code. Nevertheless, the functional meaning of mPFC entrainment to HPC theta remains a mystery. It is also unclear as to whether there are any differences in the nature of the information encoded by theta-entrained and non-entrained mPFC cells. In this review we discuss mPFC entrainment to HPC theta within the context of previous results as well as provide a more detailed analysis of the Hyman et al. (2010 data set. This re-analysis revealed that theta-entrained mPFC cells selectively encoded a variety of task relevant behaviors and stimuli while never theta-entrained mPFC cells were most strongly attuned to errors or the lack of expected rewards. In fact, these error responsive neurons were responsible for the error representations exhibited by the entire ensemble of mPFC neurons. A theta reset was also detected in the post-error period. While it is becoming increasingly evident that mPFC neurons exhibit correlates to virtually all cues and behaviors, perhaps phase-locking directs attention to the task-relevant representations required to solve a spatially based working memory task while the loss of theta-entrainment at the start of error trials may represent a shift of attention away from

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-09-05

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

  14. Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders

    NARCIS (Netherlands)

    Qi, Xin-Rui; Zhao, Juan; Liu, Ji; Fang, Hui; Swaab, Dick F; Zhou, Jiang-Ning

    The prefrontal cortex shows structural and functional alterations in mood disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its receptor TrkB are reported to be involved in depression. Here, we found that mRNA levels of key elements of retinoid signaling were significantly

  15. tDCS of medial prefrontal cortex does not enhance interpersonal trust

    NARCIS (Netherlands)

    Colzato, L.S.; Sellaro, R.; van den Wildenberg, W.P.M.; Hommel, B.

    2015-01-01

    Interpersonal trust is an essential ingredient of many social relationships. Previous research has suggested that the medial Prefrontal Cortex (mPFC) may be a critical component in mediating the degree to which people trust others. Here we assessed the role of the mPFC in modulating interpersonal

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  18. Noradrenergic action in prefrontal cortex in the late stage of memory consolidation

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

    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…

  1. Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment

    NARCIS (Netherlands)

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

    2014-01-01

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

  2. Hemodynamic Responses on Prefrontal Cortex Related to Meditation and Attentional Task

    Directory of Open Access Journals (Sweden)

    Singh eDeepeshwar

    2015-02-01

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

  3. Mapping the Hierarchical Layout of the Structural Network of the Macaque Prefrontal Cortex

    NARCIS (Netherlands)

    Goulas, A.; Uylings, H.B.M.; Stiers, P.

    2014-01-01

    A consensus on the prefrontal cortex (PFC) holds that it is pivotal for flexible behavior and the integration of the cognitive, affective, and motivational domains. Certain models have been put forth and a dominant model postulates a hierarchical anterior-posterior gradient. The structural

  4. Lateral, Not Medial, Prefrontal Cortex Contributes to Punishment and Aversive Instrumental Learning

    Science.gov (United States)

    Jean-Richard-dit-Bressel , Philip; McNally, Gavan P.

    2016-01-01

    Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral…

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

    Science.gov (United States)

    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).…

  6. Nicotinic acetylcholine receptor β2-subunits in the medial prefrontal cortex control attention

    NARCIS (Netherlands)

    Guillem, K.; Bloem, B.; Poorthuis, R.B.; Loos, M.; Smit, A.B.; Maskos, U.; Spijker, S.; Mansvelder, H.D.

    2011-01-01

    More than one-third of all people are estimated to experience mild to severe cognitive impairment as they age. Acetylcholine (ACh) levels in the brain diminish with aging, and nicotinic ACh receptor (nAChR) stimulation is known to enhance cognitive performance. The prefrontal cortex (PFC) is

  7. Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function

    NARCIS (Netherlands)

    Kamphuis, Jeanine; Baichel, Swetlana; Lancel, Marike; De Boer, Sietse F.; Koolhaas, Jaap M.; Meerlo, Peter

    Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly

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

    NARCIS (Netherlands)

    van't Wout, M; Kahn, RS; Sanfey, AG; Aleman, A

    2005-01-01

    Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex

    Science.gov (United States)

    Lindsay, Grace W.

    2017-01-01

    Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear “mixed” selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training. SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli—and in particular, to combinations of stimuli (

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

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    Laura Musazzi

    2010-01-01

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

  15. GABA levels in the ventromedial prefrontal cortex during the viewing of appetitive and disgusting food images.

    Science.gov (United States)

    Padulo, Caterina; Delli Pizzi, Stefano; Bonanni, Laura; Edden, Richard A E; Ferretti, Antonio; Marzoli, Daniele; Franciotti, Raffaella; Manippa, Valerio; Onofrj, Marco; Sepede, Gianna; Tartaro, Armando; Tommasi, Luca; Puglisi-Allegra, Stefano; Brancucci, Alfredo

    2016-10-01

    Characterizing how the brain appraises the psychological dimensions of reward is one of the central topics of neuroscience. It has become clear that dopamine neurons are implicated in the transmission of both rewarding information and aversive and alerting events through two different neuronal populations involved in encoding the motivational value and the motivational salience of stimuli, respectively. Nonetheless, there is less agreement on the role of the ventromedial prefrontal cortex (vmPFC) and the related neurotransmitter release during the processing of biologically relevant stimuli. To address this issue, we employed magnetic resonance spectroscopy (MRS), a non-invasive methodology that allows detection of some metabolites in the human brain in vivo, in order to assess the role of the vmPFC in encoding stimulus value rather than stimulus salience. Specifically, we measured gamma-aminobutyric acid (GABA) and, with control purposes, Glx levels in healthy subjects during the observation of appetitive and disgusting food images. We observed a decrease of GABA and no changes in Glx concentration in the vmPFC in both conditions. Furthermore, a comparatively smaller GABA reduction during the observation of appetitive food images than during the observation of disgusting food images was positively correlated with the scores obtained to the body image concerns sub-scale of Body Uneasiness Test (BUT). These results are consistent with the idea that the vmPFC plays a crucial role in processing both rewarding and aversive stimuli, possibly by encoding stimulus salience through glutamatergic and/or noradrenergic projections to deeper mesencephalic and limbic areas. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2007-10-17

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

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

    OpenAIRE

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

  19. Laminar and Cellular Distribution of Monoamine Receptors in Rat Medial Prefrontal Cortex

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    Noemí Santana

    2017-09-01

    Full Text Available The prefrontal cortex (PFC is deeply involved in higher brain functions, many of which are altered in psychiatric conditions. The PFC exerts a top-down control of most cortical and subcortical areas through descending pathways and is densely innervated by axons emerging from the brainstem monoamine cell groups, namely, the dorsal and median raphe nuclei (DR and MnR, respectively, the ventral tegmental area and the locus coeruleus (LC. In turn, the activity of these cell groups is tightly controlled by afferent pathways arising from layer V PFC pyramidal neurons. The reciprocal connectivity between PFC and monoamine cell groups is of interest to study the pathophysiology and treatment of severe psychiatric disorders, such as major depression and schizophrenia, inasmuch as antidepressant and antipsychotic drugs target monoamine receptors/transporters expressed in these areas. Here we review previous reports examining the presence of monoamine receptors in pyramidal and GABAergic neurons of the PFC using double in situ hybridization. Additionally, we present new data on the quantitative layer distribution (layers I, II–III, V, and VI of monoamine receptor-expressing cells in the cingulate (Cg, prelimbic (PrL and infralimbic (IL subfields of the medial PFC (mPFC. The receptors examined include serotonin 5-HT1A, 5-HT2A, 5-HT2C, and 5-HT3, dopamine D1 and D2 receptors, and α1A-, α1B-, and α1D-adrenoceptors. With the exception of 5-HT3 receptors, selectively expressed by layers I–III GABA interneurons, the rest of monoamine receptors are widely expressed by pyramidal and GABAergic neurons in intermediate and deep layers of mPFC (5-HT2C receptors are also expressed in layer I. This complex distribution suggests that monoamines may modulate the communications between PFC and cortical/subcortical areas through the activation of receptors expressed by neurons in intermediate (e.g., 5-HT1A, 5-HT2A, α1D-adrenoceptors, dopamine D1 receptors and deep

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

    Science.gov (United States)

    Powell, D A; Ginsberg, Jay P

    2005-11-01

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

  1. Prefrontal cortex plasticity mechanisms in drug seeking and relapse

    NARCIS (Netherlands)

    van den Oever, M.C.; Spijker, S.; Smit, A.B.; de Vries, T.J.

    2010-01-01

    Development of pharmacotherapy to reduce relapse rates is one of the biggest challenges in drug addiction research. The enduring nature of relapse suggests that it is maintained by long-lasting molecular and cellular adaptations in the neuronal circuitry that mediates learning and processing of

  2. PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders

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    Brielle R. Ferguson

    2018-05-01

    Full Text Available Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses. Further, their function is heavily diminished in the prefrontal cortex (PFC in numerous psychiatric diseases, including schizophrenia and autism. Previous research has demonstrated the importance of the optimal balance of excitation and inhibition (E/I in cortical circuits in maintaining the efficiency of cortical information processing. Although we are still unraveling the mechanisms of information representation in the PFC, the E/I balance seems to be crucial, as pharmacological, chemogenetic and optogenetic approaches for disrupting E/I balance induce impairments in a range of PFC-dependent behaviors. In this review, we will explore two key hypotheses. First, PV interneurons are powerful regulators of E/I balance in the PFC, and help optimize the representation and processing of supramodal information in PFC. Second, diminishing the function of PV interneurons is sufficient to generate an elaborate symptom sequelae corresponding to those observed in a range of psychiatric diseases. Then, using this framework, we will speculate on whether this circuitry could represent a platform for the development of therapeutic interventions in disorders of PFC function.

  3. Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task.

    Science.gov (United States)

    Miller, Rikki L A; Francoeur, Miranda J; Gibson, Brett M; Mair, Robert G

    2017-01-01

    The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

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

    Science.gov (United States)

    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.

  5. Normal and abnormal neuronal migration in the developing cerebral cortex

    OpenAIRE

    Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

    2002-01-01

    Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an “inside-out” gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unkno...

  6. Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine.

    Directory of Open Access Journals (Sweden)

    Ping Zhong

    2011-02-01

    Full Text Available Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC, a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT₂ receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT₁ receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.

  7. Repeated Blockade of NMDA Receptors during Adolescence Impairs Reversal Learning and Disrupts GABAergic Interneurons in Rat Medial Prefrontal Cortex

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    Jitao eLi

    2016-03-01

    Full Text Available Adolescence is of particular significance to schizophrenia, since psychosis onset typically occurs in this critical period. Based on the N-methyl-D-aspartate (NMDA receptor hypofunction hypothesis of schizophrenia, in this study, we investigated whether and how repeated NMDA receptor blockade during adolescence would affect GABAergic interneurons in rat medial prefrontal cortex (mPFC and mPFC-mediated cognitive functions. Specifically, adolescent rats were subjected to intraperitoneal administration of MK-801 (0.1, 0.2, 0.4 mg/kg, a non-competitive NMDA receptor antagonist, for 14 days and then tested for reference memory and reversal learning in the water maze. The density of parvabumin (PV-, calbindin (CB- and calretinin (CR-positive neurons in mPFC were analyzed at either 24 hours or 7 days after drug cessation. We found that MK-801 treatment delayed reversal learning in the water maze without affecting initial acquisition. Strikingly, MK-801 treatment also significantly reduced the density of PV+ and CB+ neurons, and this effect persisted for 7 days after drug cessation at the dose of 0.2 mg/kg. We further demonstrated that the reduction in PV+ and CB+ neuron densities was ascribed to a downregulation of the expression levels of PV and CB, but not to neuronal death. These results parallel the behavioral and neuropathological changes of schizophrenia and provide evidence that adolescent NMDA receptors antagonism offers a useful tool for unraveling the etiology of the disease.

  8. The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

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    Pedro F. M. Ribeiro

    2013-09-01

    Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

  9. Effects of transcranial direct current stimulation of the motor cortex on prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study.

    Science.gov (United States)

    Muthalib, Makii; Kan, Benjamin; Nosaka, Kazunori; Perrey, Stephane

    2013-01-01

    This study investigated whether manipulation of motor cortex excitability by transcranial direct current stimulation (tDCS) modulates neuromuscular fatigue and functional near-infrared spectroscopy (fNIRS)-derived prefrontal cortex (PFC) activation. Fifteen healthy men (27.7 ± 8.4 years) underwent anodal (2 mA, 10 min) and sham (2 mA, first 30 s only) tDCS delivered to the scalp over the right motor cortex. Subjects initially performed a baseline sustained submaximal (30 % maximal voluntary isometric contraction, MVC) isometric contraction task (SSIT) of the left elbow flexors until task failure, which was followed 50 min later by either an anodal or sham treatment condition, then a subsequent posttreatment SSIT. Endurance time (ET), torque integral (TI), and fNIRS-derived contralateral PFC oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentration changes were determined at task failure. Results indicated that during the baseline and posttreatment SSIT, there were no significant differences in TI and ET, and increases in fNIRS-derived PFC activation at task failure were observed similarly regardless of the tDCS conditions. This suggests that the PFC neuronal activation to maintain muscle force production was not modulated by anodal tDCS.

  10. Cellular properties of principal neurons in the rat entorhinal cortex. I. The lateral entorhinal cortex

    NARCIS (Netherlands)

    Canto, C.B.; Witter, M.P.

    2012-01-01

    The lateral entorhinal cortex (LEC) provides a major cortical input to the hippocampal formation, equaling that of the medial entorhinal cortex (MEC). To understand the functional contributions made by LEC, basic knowledge of individual neurons, in the context of the intrinsic network, is needed.

  11. Prefrontal cortex NG2 glia undergo a developmental switch in their responsiveness to exercise.

    Science.gov (United States)

    Tomlinson, Lyl; Huang, Po Hsuan; Colognato, Holly

    2018-03-22

    Aerobic exercise is known to influence brain function, e.g., enhancing executive function in both children and adults, with many of these influences being attributed to alterations in neurogenesis and neuronal function. Yet oligodendroglia in adult brains have also been reported to be highly responsive to exercise, including in the prefrontal cortex (PFC), a late myelinating region implicated in working memory. However, whether exercise affects oligodendroglia or myelination in juveniles, either in the PFC or in other brain regions, remains unknown. To address this, both juvenile and young adult mice were provided free access to running wheels for four weeks followed by an analysis of oligodendrocyte development and myelination in the PFC and the corpus callosum, a major white matter tract. Working memory and PFC NG2+ cell development were both affected by exercise in juvenile mice, yet surprisingly these exercise-mediated effects were distinct in juveniles and young adults. In the PFC, NG2+ cell proliferation was increased in exercising juveniles, but not young adults, whereas newly-born oligodendrocyte production was increased in exercising young adults, but not juveniles. Although no overall changes in myelin genes were found, elevated levels of Monocarboxylate Transporter 1, a glial lactate transporter important during active myelination, were found in the PFC of exercising young adults. Overall our findings reveal that long-term exercise modulates PFC glial development and does so differentially in juvenile and young adult mice, providing insight into the cellular responses that may underlie cognitive benefits to teenagers and young adults in response to exercise. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

  12. Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

    Science.gov (United States)

    Areal, Lorena Bianchine; Herlinger, Alice Laschuk; Pelição, Fabrício Souza; Martins-Silva, Cristina; Pires, Rita Gomes Wanderley

    2017-08-01

    Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Affective and cognitive prefrontal cortex projections to the lateral habenula in humans.

    Directory of Open Access Journals (Sweden)

    Karin eVadovičová

    2014-10-01

    Full Text Available Anterior insula (AI and dorsal ACC (dACC are known to process information about pain, loss, adversities, bad, harmful or suboptimal choices and consequences that threaten survival or well-being. Also pregenual ACC (pgACC is linked to loss and pain, being activated by sad thoughts and regrets. Lateral habenula (LHb is stimulated by predicted and received pain, discomfort, aversive outcome, loss. Its chronic stimulation makes us feel worse/low and gradually stops us choosing and moving for the suboptimal or punished choices, by direct and indirect (via rostromedial tegmental nucleus RMTg inhibition of DRN and VTA/SNc. The response selectivity of LHb neurons suggests their cortical input from affective and cognitive evaluative regions that make expectations about bad, unpleasant or suboptimal outcomes. Based on these facts we predicted direct dACC, pgACC and AI projections to LHb, which form part of an adversity processing circuit that learns to avoid bad outcomes by suppressing dopamine and serotonin signal. To test this connectivity we used Diffusion Tensor Imaging (DTI. We found dACC, pgACC, AI and caudolateral OFC projections to LHb. We predicted no corticohabenular projections from the reward processing regions: medial OFC (mOFC and ventral ACC (vACC because both respond most strongly to good, high valued stimuli and outcomes, inducing dopamine and serotonin release. This lack of LHb projections was confirmed for vACC and likely for mOFC. The surprising findings were the corticohabenular projections from the cognitive prefrontal cortex regions, known for flexible reasoning, planning and combining whatever information are relevant for reaching current goals. We propose that the prefrontohabenular projections provide a teaching signal for value-based choice behaviour, to learn to deselect, avoid or inhibit the potentially harmful, low valued or wrong choices, goals, strategies, predictions and ways of doing things, to prevent bad or suboptimal

  14. Executive function and cerebral blood flow on dorsolateral prefrontal cortex in cases of subcortical infarction

    International Nuclear Information System (INIS)

    Hasegawa, Akira; Utsumi, Hiroya

    2006-01-01

    In order to clarify the extent of dysexecutive function of patients with subcortical infarctions, participants of this study underwent neuropsychological tests and single photon emission computerized tomography (SPECT). These participants were categorized into two groups; patients with basal ganglia lesions (BG group) (n=5) and those with white matter lesions (WM group) (n=12). Participants were administered executive function tests as a part of a comprehensive neuropsychological battery. Administered executive measures included the Wisconsin Card Sorting Test (WCST), the Ruff Figural Fluency Test (RFFT), the Controlled Oral Word Association Test (COWAT), and the Trait Making Test; Parts A and B. There were no group differences in their age, years of education and global cognitive performance. Student's t-tests were conducted to determine group differences in executive function. As a result, the number of total errors, the number of perseverative errors and the number of categories completed on the WCST were significantly worse for the BG group than for the WM group. These groups did not differ on other measures administered. In addition, all participants underwent SPECT, and their results were compared with the normal control data. Hypoperfusion was found on parts of the bilateral frontal, temporal, and parietal lobes for the BG and WM groups. These tendencies stood out in the right hemisphere of the BG group. The BG group exhibited decreased cerebral blood flow (CBF) on the area of right side dorsolateral prefrontal cortex (DLPFC) (e.g., Brodmann area 44). These analyses revealed that individuals with BG lesions showed significant executive declines that might be associated with decreased CBF in the subcortical-frontal system. It may support the idea that BG is connected with DLPFC via frontal-subcortical neuronal circuit. Patients with BG lesions may experience dysexecutive function due to the phenomenon of diaschisis from the disruption of this circuit. (author)

  15. GABA content within the ventromedial prefrontal cortex is related to trait anxiety.

    Science.gov (United States)

    Delli Pizzi, Stefano; Padulo, Caterina; Brancucci, Alfredo; Bubbico, Giovanna; Edden, Richard A; Ferretti, Antonio; Franciotti, Raffaella; Manippa, Valerio; Marzoli, Daniele; Onofrj, Marco; Sepede, Gianna; Tartaro, Armando; Tommasi, Luca; Puglisi-Allegra, Stefano; Bonanni, Laura

    2016-05-01

    The ventromedial prefrontal cortex (vmPFC) plays a key role in emotion processing and regulation. vmPFC dysfunction may lead to disinhibition of amygdala causing high anxiety levels. γ-Aminobutyric acid (GABA) inter-neurons within vmPFC shape the information flow to amygdala. Thus, we hypothesize that GABA content within vmPFC could be relevant to trait anxiety. Forty-three healthy volunteers aged between 20 and 88 years were assessed for trait anxiety with the Subscale-2 of the State-Trait-Anxiety Inventory (STAI-Y2) and were studied with proton magnetic resonance spectroscopy to investigate GABA and Glx (glutamate+glutamine) contents within vmPFC. Total creatine (tCr) was used as internal reference. Partial correlations assessed the association between metabolite levels and STAI-Y2 scores, removing the effect of possible nuisance factors including age, educational level, volumes of gray matter and white matter within magnetic resonance spectroscopy voxel. We observed a positive relationship between GABA/tCr and STAI-Y2 scores. No significant relationships were found between Glx/tCr and STAI-Y2 and between tCr/water and STAI-Y2. No differences were found between males and females as regards to age, STAI-Y2, GABA/tCr, Glx/tCr, tCr/water, gray matter and white matter volumes. We suggest a close relationship between GABA content within vmPFC and trait anxiety providing new insights in the physiology of emotional brain. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders.

    Directory of Open Access Journals (Sweden)

    Kasey N Davis

    Full Text Available Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA, the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC. No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517 in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.

  17. Whole genome grey and white matter DNA methylation profiles in dorsolateral prefrontal cortex.

    Science.gov (United States)

    Sanchez-Mut, Jose Vicente; Heyn, Holger; Vidal, Enrique; Delgado-Morales, Raúl; Moran, Sebastian; Sayols, Sergi; Sandoval, Juan; Ferrer, Isidre; Esteller, Manel; Gräff, Johannes

    2017-06-01

    The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood. Herein, we determined the DNA methylation patterns of grey and white matter of dorsolateral prefrontal cortex (Brodmann area 9), an important region for higher cognitive skills that is particularly affected in various neurological diseases. For avoiding interindividual differences, we analyzed white and grey matter from the same donor using whole genome bisulfite sequencing, and for validating their biological significance, we used Infinium HumanMethylation450 BeadChip and pyrosequencing in ten and twenty independent samples, respectively. The combination of these analysis indicated robust grey-white matter differences in DNA methylation. What is more, cell type-specific markers were enriched among the most differentially methylated genes. Interestingly, we also found an outstanding number of grey-white matter differentially methylated genes that have previously been associated with Alzheimer's, Parkinson's, and Huntington's disease, as well as Multiple and Amyotrophic lateral sclerosis. The data presented here thus constitute an important resource for future studies not only to gain insight into brain regional as well as grey and white matter differences, but also to unmask epigenetic alterations that might underlie neurological and neurodegenerative diseases. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Goel, Vinod; Dolan, Raymond J

    2004-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-03-01

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

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  1. Bupropion Administration Increases Resting-State Functional Connectivity in Dorso-Medial Prefrontal Cortex.

    Science.gov (United States)

    Rzepa, Ewelina; Dean, Zola; McCabe, Ciara

    2017-06-01

    Patients on the selective serotonergic reuptake inhibitors like citalopram report emotional blunting. We showed previously that citalopram reduces resting-state functional connectivity in healthy volunteers in a number of brain regions, including the dorso-medial prefrontal cortex, which may be related to its clinical effects. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and is not reported to cause emotional blunting. However, how bupropion affects resting-state functional connectivity in healthy controls remains unknown. Using a within-subjects, repeated-measures, double-blind, crossover design, we examined 17 healthy volunteers (9 female, 8 male). Volunteers received 7 days of bupropion (150 mg/d) and 7 days of placebo treatment and underwent resting-state functional Magnetic Resonance Imaging. We selected seed regions in the salience network (amygdala and pregenual anterior cingulate cortex) and the central executive network (dorsal medial prefrontal cortex). Mood and anhedonia measures were also recorded and examined in relation to resting-state functional connectivity. Relative to placebo, bupropion increased resting-state functional connectivity in healthy volunteers between the dorsal medial prefrontal cortex seed region and the posterior cingulate cortex and the precuneus cortex, key parts of the default mode network. These results are opposite to that which we found with 7 days treatment of citalopram in healthy volunteers. These results reflect a different mechanism of action of bupropion compared with selective serotonergic reuptake inhibitors. These results help explain the apparent lack of emotional blunting caused by bupropion in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  2. Neuronal Migration and Neuronal Migration Disorder in Cerebral Cortex

    OpenAIRE

    SUN, Xue-Zhi; TAKAHASHI, Sentaro; GUI, Chun; ZHANG, Rui; KOGA, Kazuo; NOUYE, Minoru; MURATA, Yoshiharu

    2002-01-01

    Neuronal cell migration is one of the most significant features during cortical development. After final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. Neuronal migration is guided by radial glial fibers and also needs proper receptors, ligands, and other unknown extracellular factors, requests local signaling (e.g. some emitted by the Cajal-Retz...

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

    Science.gov (United States)

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

    2011-03-01

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

  4. Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

    Science.gov (United States)

    Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

    2007-09-15

    Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

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

    Science.gov (United States)

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

    2012-01-29

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

  6. The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making

    Directory of Open Access Journals (Sweden)

    Regina A. Weilbächer

    2016-12-01

    Full Text Available Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making.

  7. Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation.

    Directory of Open Access Journals (Sweden)

    Armita Golkar

    Full Text Available The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC and the lateral orbitofrontal cortex (OFC contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

  8. Neural activity in ventral medial prefrontal cortex is modulated more before approach than avoidance during reinforced and extinction trial blocks.

    Science.gov (United States)

    Gentry, Ronny N; Roesch, Matthew R

    2018-04-16

    Ventromedial prefrontal cortex (vmPFC) is thought to provide regulatory control over Pavlovian fear responses and has recently been implicated in appetitive approach behavior, but much less is known about its role in contexts where appetitive and aversive outcomes can be obtained and avoided, respectively. To address this issue, we recorded from single neurons in vmPFC while male rats performed our combined approach and avoidance task under reinforced and non-reinforced (extinction) conditions. Surprisingly, we found that cues predicting reward modulated cell firing in vmPFC more often and more robustly than cues preceding avoidable shock; additionally, firing of vmPFC neurons was both response (press or no-press) and outcome (reinforced or extinction) selective. These results suggest a complex role for vmPFC in regulating behavior and supports its role in appetitive contexts during both reinforced and non-reinforced conditions. SIGNIFICANCE STATEMENT Selecting context-appropriate behaviors to gain reward or avoid punishment is critical for survival. While the role of ventromedial prefrontal cortex (vmPFC) in mediating fear responses is well-established, vmPFC has also been implicated in the regulation of reward-guided approach and extinction. Many studies have used indirect methods and simple behavioral procedures to study vmPFC, which leaves the literature incomplete. We recorded vmFPC neural activity during a complex cue-driven combined approach and avoidance task and during extinction. Surprisingly, we found very little vmPFC modulation to cues predicting avoidable shock, while cues predicting reward approach robustly modulated vmPFC firing in a response- and outcome-selective manner. This suggests a more complex role for vmPFC than current theories suggest, specifically regarding context-specific behavioral optimization. Copyright © 2018 the authors.

  9. Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex

    NARCIS (Netherlands)

    Canto, C.B.; Witter, M.P.

    2012-01-01

    Principal neurons in different medial entorhinal cortex (MEC) layers show variations in spatial modulation that stabilize between 15 and 30 days postnatally. These in vivo variations are likely due to differences in intrinsic membrane properties and integrative capacities of neurons. The latter

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

    Science.gov (United States)

    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.

  11. The amygdala and ventromedial prefrontal cortex: functional contributions and dysfunction in psychopathy

    OpenAIRE

    Blair, R.J.R

    2008-01-01

    The current paper examines the functional contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) and the evidence that the functioning of these systems is compromised in individuals with psychopathy. The amygdala is critical for the formation of stimulus–reinforcement associations, both punishment and reward based, and the processing of emotional expressions. vmPFC is critical for the representation of reinforcement expectancies and, owing to this, decision making. Neuropsyc...

  12. Impaired Facilitatory Mechanisms of Auditory Attention After Damage of the Lateral Prefrontal Cortex

    OpenAIRE

    Bidet-Caulet, Aurélie; Buchanan, Kelly G.; Viswanath, Humsini; Black, Jessica; Scabini, Donatella; Bonnet-Brilhault, Frédérique; Knight, Robert T.

    2014-01-01

    There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, ...

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

    OpenAIRE

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

    2017-01-01

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

  14. Dorsolateral Prefrontal Cortex Drives Mesolimbic Dopaminergic Regions to Initiate Motivated Behavior

    OpenAIRE

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

    2011-01-01

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

  15. Co-activation-based parcellation of the lateral prefrontal cortex delineates the inferior frontal junction area

    OpenAIRE

    Muhle-Karbe, Paul Simon; Derrfuss, Jan; Lynn, Maggie; Neubert, Franz Xaver; Fox, Peter; Brass, Marcel; Eickhoff, Simon

    2016-01-01

    The inferior frontal junction (IFJ) area, a small region in the posterior lateral prefrontal cortex (LPFC), has received increasing interest in recent years due to its central involvement in the control of action, attention, and memory. Yet, both its function and anatomy remain controversial. Here, we employed a meta-analytic parcellation of the left LPFC to show that the IFJ can be isolated based on its specific functional connections. A seed region, oriented along the left inferior frontal ...

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

    Science.gov (United States)

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

    2017-07-01

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

  17. Neuropsychiatric effects of neurodegeneration of the medial vs. lateral ventral prefrontal cortex in humans

    OpenAIRE

    Huey, Edward D.; Lee, Seonjoo; Brickman, Adam M.; Manoochehri, Masood; Griffith, Erica; Devanand, D.P.; Stern, Yaakov; Grafman, Jordan

    2015-01-01

    Animal evidence suggests that a brain network involving the medial and rostral ventral prefrontal cortex (PFC) is central for threat response and arousal and a network involving the lateral and caudal PFC plays an important role in reward learning and behavioral control. In this study, we contrasted the neuropsychiatric effects of degeneration of the medial versus lateral PFC in 43 patients with Frontotemporal dementia and 11 patients with Corticobasal Syndrome using MRI, the Neuropsychiatric...

  18. Differences between Neural Activity in Prefrontal Cortex and Striatum during Learning of Novel Abstract Categories

    OpenAIRE

    Antzoulatos, Evan G.; Miller, Earl K.

    2011-01-01

    Learning to classify diverse experiences into meaningful groups, like categories, is fundamental to normal cognition. To understand its neural basis, we simultaneously recorded from multiple electrodes in the lateral prefrontal cortex and dorsal striatum, two interconnected brain structures critical for learning. Each day, monkeys learned to associate novel, abstract dot-based categories with a right vs. left saccade. Early on, when they could acquire specific stimulus-response associations, ...

  19. The Role of Medial Prefrontal Cortex in Memory and Decision Making

    OpenAIRE

    Euston, David R.; Gruber, Aaron J.; McNaughton, Bruce L.

    2012-01-01

    Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time-scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, ...

  20. Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia

    OpenAIRE

    Hashimoto, T; Arion, D; Unger, T; Maldonado-Avilés, JG; Morris, HM; Volk, DW; Mirnics, K; Lewis, DA

    2007-01-01

    In subjects with schizophrenia, impairments in working memory are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction appears to be due, at least in part, to abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory circuitry. To test the hypothesis that altered GABA-mediated circuitry in the DLPFC of subjects with schizophrenia reflects expression changes of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmis...

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

    Directory of Open Access Journals (Sweden)

    Erik William Asp

    2013-05-01

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

  2. Spindle neurons of the human anterior cingulate cortex

    Science.gov (United States)

    Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

  3. Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

    Science.gov (United States)

    Rubino, Tiziana; Prini, Pamela; Piscitelli, Fabiana; Zamberletti, Erica; Trusel, Massimo; Melis, Miriam; Sagheddu, Claudia; Ligresti, Alessia; Tonini, Raffaella; Di Marzo, Vincenzo; Parolaro, Daniela

    2015-01-01

    Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Goel, Vinod; Dolan, Raymond J

    2003-12-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  6. Prefrontal Cortex Networks Shift from External to Internal Modes during Learning

    Science.gov (United States)

    Brincat, Scott L.

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

  9. Prefrontal Neurons Represent Motion Signals from Across the Visual Field But for Memory-Guided Comparisons Depend on Neurons Providing These Signals.

    Science.gov (United States)

    Wimmer, Klaus; Spinelli, Philip; Pasternak, Tatiana

    2016-09-07

    Visual decisions often involve comparisons of sequential stimuli that can appear at any location in the visual field. The lateral prefrontal cortex (LPFC) in nonhuman primates, shown to play an important role in such comparisons, receives information about contralateral stimuli directly from sensory neurons in the same hemisphere, and about ipsilateral stimuli indirectly from neurons in the opposite hemisphere. This asymmetry of sensory inputs into the LPFC poses the question of whether and how its neurons incorporate sensory information arriving from the two hemispheres during memory-guided comparisons of visual motion. We found that, although responses of individual LPFC neurons to contralateral stimuli were stronger and emerged 40 ms earlier, they carried remarkably similar signals about motion direction in the two hemifields, with comparable direction selectivity and similar direction preferences. This similarity was also apparent around the time of the comparison between the current and remembered stimulus because both ipsilateral and contralateral responses showed similar signals reflecting the remembered direction. However, despite availability in the LPFC of motion information from across the visual field, these "comparison effects" required for the comparison stimuli to appear at the same retinal location. This strict dependence on spatial overlap of the comparison stimuli suggests participation of neurons with localized receptive fields in the comparison process. These results suggest that while LPFC incorporates many key aspects of the information arriving from sensory neurons residing in opposite hemispheres, it continues relying on the interactions with these neurons at the time of generating signals leading to successful perceptual decisions. Visual decisions often involve comparisons of sequential visual motion that can appear at any location in the visual field. We show that during such comparisons, the lateral prefrontal cortex (LPFC) contains

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

    Science.gov (United States)

    Carlson, Joshua M; Depetro, Emily; Maxwell, Joshua; Harmon-Jones, Eddie; Hajcak, Greg

    2015-08-30

    Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal.

    Science.gov (United States)

    Huang, Hao; Ghosh, Prabhat; van den Pol, Anthony N

    2006-03-01

    The paraventricular thalamic nucleus (PVT) receives one of the most dense innervations by hypothalamic hypocretin/orexin (Hcrt) neurons, which play important roles in sleep-wakefulness, attention, and autonomic function. The PVT projects to several loci, including the medial prefrontal cortex (mPFC), a cortical region involved in associative function and attention. To study the effect of Hcrt on excitatory PVT neurons that project to the mPFC, we used a new line of transgenic mice expressing green fluorescent protein (GFP) under the control of the vesicular glutamate-transporter-2 promoter. These neurons were retrogradely labeled with cholera toxin subunit B that had been microinjected into the mPFC. Membrane characteristics and responses to hypocretin-1 and -2 (Hcrt-1 and -2) were studied using whole cell recording (n > 300). PVT neurons showed distinct membrane properties including inward rectification, H-type potassium currents, low threshold spikes, and spike frequency adaptation. Cortically projecting neurons were depolarized and excited by Hcrt-2. Hcrt-2 actions were stronger than those of Hcrt-1, and the action persisted in TTX and in low calcium/high magnesium artificial cerebrospinal fluid, consistent with direct actions mediated by Hcrt receptor-2. Two mechanisms of Hcrt excitation were found: an increase in input resistance caused by closure of potassium channels and activation of nonselective cation channels. The robust excitation evoked by Hcrt-2 on cortically projecting glutamate PVT neurons could generate substantial excitation in multiple layers of the mPFC, adding to the more selective direct excitatory actions of Hcrt in the mPFC and potentially increasing cortical arousal and attention to limbic or visceral states.

  12. Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions.

    Science.gov (United States)

    Perry, Jennifer L; Joseph, Jane E; Jiang, Yang; Zimmerman, Rick S; Kelly, Thomas H; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P; Bardo, Michael T

    2011-01-01

    Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Diverse coupling of neurons to populations in sensory cortex.

    Science.gov (United States)

    Okun, Michael; Steinmetz, Nicholas; Cossell, Lee; Iacaruso, M Florencia; Ko, Ho; Barthó, Péter; Moore, Tirin; Hofer, Sonja B; Mrsic-Flogel, Thomas D; Carandini, Matteo; Harris, Kenneth D

    2015-05-28

    A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-07-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  16. Age- and Sex-Dependent Impact of Repeated Social Stress on Intrinsic and Synaptic Excitability of the Rat Prefrontal Cortex.

    Science.gov (United States)

    Urban, Kimberly R; Valentino, Rita J

    2017-01-01

    Stress is implicated in psychiatric illnesses that are characterized by impairments in cognitive functions that are mediated by the medial prefrontal cortex (mPFC). Because sex and age determine stress vulnerability, the effects of repeated social stress occurring during early adolescence, mid-adolescence, or adulthood on the cellular properties of male and female rat mPFC Layer V neurons in vitro were examined. Repeated resident-intruder stress produced age- and sex-specific effects on mPFC intrinsic and synaptic excitability. Mid-adolescents were particularly vulnerable to effects on intrinsic excitability. The maximum number of action potentials (APs) evoked by increasing current intensity was robustly decreased in stressed male and female mid-adolescent rats compared with age-matched controls. These effects were associated with stress-induced changes in AP half-width, amplitude, threshold, and input resistance. Social stress at all ages generally decreased synaptic excitability by decreasing the amplitude of spontaneous excitatory postsynaptic potentials. The results suggest that whereas social stress throughout life can diminish the influence of afferents driving the mPFC, social stress during mid-adolescence additionally affects intrinsic characteristics of mPFC neurons that determine excitability. The depressant effects of social stress on intrinsic and synaptic mPFC neurons may underlie its ability to affect executive functions and emotional responses, particularly during adolescence. © The Author 2016. Published by Oxford University Press.

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

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    Erik eAsp

    2012-07-01

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

  19. Decoding the dopamine signal in macaque prefrontal cortex: a simulation study using the Cx3Dp simulator.

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    Full Text Available Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated 'teaching' signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson's disease, or induced through drugs blocking dopamine reuptake.

  20. Decoding the Dopamine Signal in Macaque Prefrontal Cortex: A Simulation Study Using the Cx3Dp Simulator

    Science.gov (United States)

    Spühler, Isabelle Ayumi; Hauri, Andreas

    2013-01-01

    Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake. PMID:23951205

  1. Cell-Type Specific Changes in Glial Morphology and Glucocorticoid Expression During Stress and Aging in the Medial Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Thomas E. Chan

    2018-05-01

    Full Text Available Repeated exposure to stressors is known to produce large-scale remodeling of neurons within the prefrontal cortex (PFC. Recent work suggests stress-related forms of structural plasticity can interact with aging to drive distinct patterns of pyramidal cell morphological changes. However, little is known about how other cellular components within PFC might be affected by these challenges. Here, we examined the effects of stress exposure and aging on medial prefrontal cortical glial subpopulations. Interestingly, we found no changes in glial morphology with stress exposure but a profound morphological change with aging. Furthermore, we found an upregulation of non-nuclear glucocorticoid receptors (GR with aging, while nuclear levels remained largely unaffected. Both changes are selective for microglia, with no stress or aging effect found in astrocytes. Lastly, we show that the changes found within microglia inversely correlated with the density of dendritic spines on layer III pyramidal cells. These findings suggest microglia play a selective role in synaptic health within the aging brain.

  2. Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

    Science.gov (United States)

    Moorman, David E.; Aston-Jones, Gary

    2015-01-01

    The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior (“go”) whereas ventral/infralimbic (IL) mPFC is thought to control behavioral suppression (“stop”). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response–outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not. PMID:26170333

  3. Anterior cingulate cortex instigates adaptive switches in choice by integrating immediate and delayed components of value in ventromedial prefrontal cortex.

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    Economides, Marcos; Guitart-Masip, Marc; Kurth-Nelson, Zeb; Dolan, Raymond J

    2014-02-26

    Actions can lead to an immediate reward or punishment and a complex set of delayed outcomes. Adaptive choice necessitates the brain track and integrate both of these potential consequences. Here, we designed a sequential task whereby the decision to exploit or forego an available offer was contingent on comparing immediate value and a state-dependent future cost of expending a limited resource. Crucially, the dynamics of the task demanded frequent switches in policy based on an online computation of changing delayed consequences. We found that human subjects choose on the basis of a near-optimal integration of immediate reward and delayed consequences, with the latter computed in a prefrontal network. Within this network, anterior cingulate cortex (ACC) was dynamically coupled to ventromedial prefrontal cortex (vmPFC) when adaptive switches in choice were required. Our results suggest a choice architecture whereby interactions between ACC and vmPFC underpin an integration of immediate and delayed components of value to support flexible policy switching that accommodates the potential delayed consequences of an action.

  4. Normal and abnormal neuronal migration in the developing cerebral cortex.

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    Sun, Xue-Zhi; Takahashi, Sentaro; Cui, Chun; Zhang, Rui; Sakata-Haga, Hiromi; Sawada, Kazuhiko; Fukui, Yoshihiro

    2002-08-01

    Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unknown extracellular factors, and local signaling to stop neuronal migration. This process is also highly sensitive to various physical, chemical and biological agents as well as to genetic mutations. Any disturbance of the normal process may result in neuronal migration disorder. Such neuronal migration disorder is believed as major cause of both gross brain malformation and more special cerebral structural and functional abnormalities in experimental animals and in humans. An increasing number of instructive studies on experimental models and several genetic model systems of neuronal migration disorder have established the foundation of cortex formation and provided deeper insights into the genetic and molecular mechanisms underlying normal and abnormal neuronal migration.

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

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    Hoftman, Gil D.; Lewis, David A.

    2011-01-01

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

  6. Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

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    Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

    2017-08-01

    Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

  7. Distinct regions of prefrontal cortex are associated with the controlled retrieval and selection of social information.

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    Satpute, Ajay B; Badre, David; Ochsner, Kevin N

    2014-05-01

    Research in social neuroscience has uncovered a social knowledge network that is particularly attuned to making social judgments. However, the processes that are being performed by both regions within this network and those outside of this network that are nevertheless engaged in the service of making a social judgment remain unclear. To help address this, we drew upon research in semantic memory, which suggests that making a semantic judgment engages 2 distinct control processes: A controlled retrieval process, which aids in bringing goal-relevant information to mind from long-term stores, and a selection process, which aids in selecting the information that is goal-relevant from the information retrieved. In a neuroimaging study, we investigated whether controlled retrieval and selection for social information engage distinct portions of both the social knowledge network and regions outside this network. Controlled retrieval for social information engaged an anterior ventrolateral portion of the prefrontal cortex, whereas selection engaged both the dorsomedial prefrontal cortex and temporoparietal junction within the social knowledge network. These results suggest that the social knowledge network may be more involved with the selection of social information than the controlled retrieval of it and incorporates lateral prefrontal regions in accessing memory for making social judgments.

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

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    Saskia Koehler

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

  9. Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation.

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    Alexandra Dumitriu

    2012-06-01

    Full Text Available Parkinson disease (PD is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9 of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1 transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes, suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs selected from a recent meta-analysis of PD genome-wide association studies (GWAS were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK gene and a probe in the spermine oxidase (SMOX gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.

  10. Juvenile social experience and differential age-related changes in the dendritic morphologies of subareas of the prefrontal cortex in rats.

    Science.gov (United States)

    Himmler, Brett T; Mychasiuk, Richelle; Nakahashi, Ayuno; Himmler, Stephanie M; Pellis, Sergio M; Kolb, Bryan

    2018-04-01

    Juvenile social interactions have been shown to influence the dendritic complexity of neurons in the prefrontal cortex (PFC). In particular, social play induces pruning of the cells in the medial prefrontal cortex (mPFC), whereas interacting with multiple partners, whether those interactions involve play or not, increases the complexity of cells in the orbital frontal cortex (OFC). Previous studies suggest that these changes differ in their stability during adulthood. In the present study, rats were reared in groups of either four (quads) or two (pairs) and the brains of the rats from each rearing condition were then harvested at 60 days (i.e., shortly after sexual maturity) and 100 days (i.e., fully adult). The rats housed with multiple partners had more complex neurons of the OFC at 60 days and this complexity declined to a comparable level to that of pair housed rats by 100 days. In contrast, the play-induced changes of the mPFC remained similar at both ages. These findings suggest that the changes in the PFC induced by different social experiences in the juvenile period differ in how long they are maintained in adulthood. Differences in the functions regulated by the OFC and the mPFC are considered with regard to these differences in the stability of juvenile-induced neural changes. © 2017 Wiley Periodicals, Inc.

  11. Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Arion, D; Corradi, J P; Tang, S; Datta, D; Boothe, F; He, A; Cacace, A M; Zaczek, R; Albright, C F; Tseng, G; Lewis, D A

    2015-11-01

    Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3 and, to a lesser extent, in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell-type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression, specifically in DLPFC layer 3 or 5 pyramidal cells, would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness. We also sought to determine the impact of other variables, such as a diagnosis of schizoaffective disorder or medication use at the time of death, on the patterns of gene expression in pyramidal neurons. Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser microdissection from 36 subjects with schizophrenia or schizoaffective disorder and matched normal comparison subjects. The mRNA from cell collections was subjected to transcriptome profiling by microarray followed by quantitative PCR validation. Expression of genes involved in mitochondrial (MT) or ubiquitin-proteasome system (UPS) functions were markedly downregulated in the patient group (P-values for MT-related and UPS-related pathways were schizoaffective disorder subjects (diagnosis of schizoaffective disorder was the most significant covariate, Pschizoaffective disorder, providing a potential molecular-cellular basis of differences in clinical phenotypes.

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

    Science.gov (United States)

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

    2009-09-01

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

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

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    Rebecca M Shansky

    2013-04-01

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

  14. Functional heterogeneity of conflict, error, task-switching, and unexpectedness effects within medial prefrontal cortex.

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    Nee, Derek Evan; Kastner, Sabine; Brown, Joshua W

    2011-01-01

    The last decade has seen considerable discussion regarding a theoretical account of medial prefrontal cortex (mPFC) function with particular focus on the anterior cingulate cortex. The proposed theories have included conflict detection, error likelihood prediction, volatility monitoring, and several distinct theories of error detection. Arguments for and against particular theories often treat mPFC as functionally homogeneous, or at least nearly so, despite some evidence for distinct functional subregions. Here we used functional magnetic resonance imaging (fMRI) to simultaneously contrast multiple effects of error, conflict, and task-switching that have been individually construed in support of various theories. We found overlapping yet functionally distinct subregions of mPFC, with activations related to dominant error, conflict, and task-switching effects successively found along a rostral-ventral to caudal-dorsal gradient within medial prefrontal cortex. Activations in the rostral cingulate zone (RCZ) were strongly correlated with the unexpectedness of outcomes suggesting a role in outcome prediction and preparing control systems to deal with anticipated outcomes. The results as a whole support a resolution of some ongoing debates in that distinct theories may each pertain to corresponding distinct yet overlapping subregions of mPFC. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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

    2013-10-01

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

  16. Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.

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

    2008-05-01

    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 whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and

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

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.

    2015-01-01

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

  18. Medial Prefrontal Cortex Activation Is Commonly Invoked by Reputation of Self and Romantic Partners

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    Kawamichi, Hiroaki; Sasaki, Akihiro T.; Matsunaga, Masahiro; Yoshihara, Kazufumi; Takahashi, Haruka K.; Tanabe, Hiroki C.; Sadato, Norihiro

    2013-01-01

    The reputation of others influences partner selection in human cooperative behaviors through verbal reputation representation. Although the way in which humans represent the verbal reputations of others is a pivotal issue for social neuroscience, the neural correlates underlying the representation of verbal reputations of others are unclear. Humans primarily depend on self-evaluation when assessing reputation of self. Likewise, humans might primarily depend on self-evaluation of others when representing their reputation. As interaction promotes the formation of more nuanced, individualized impressions of an interaction partner, humans tend to form self-evaluations of persons with whom they are intimate in their daily life. Thus, we hypothesized that the representation of reputation of others is modulated by intimacy due to one’s own evaluation formation of that person. To test this hypothesis, we conducted a functional magnetic resonance imaging experiment with 11 pairs of romantic partners while they viewed an evaluation of a target person (self, partner [intimate other], or stranger [non-intimate other]), made by other evaluators. When compared with strangers, viewing evaluations of self and partner activated overlapping regions in the medial prefrontal cortex. Verbal reputation of self-specific activation was found in the precuneus, which represents self-related processing. The data suggest that midline structures represent reputation of self. In addition, intimacy-modulated activation in the medial prefrontal cortex suggests that the verbal reputation of intimate others is represented similarly to reputation of self. These results suggest that the reputation representation in the medial prefrontal cortex is engaged by verbal reputation of self and intimate others stemming from both own and other evaluators’ judgments. PMID:24086409

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

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    Massimiliano Conson

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

  20. Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

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    Neves, Ricardo M; van Keulen, Silvia; Yang, Mingyu; Logothetis, Nikos K; Eschenko, Oxana

    2018-03-01

    The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α 2 -adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information

  1. Primate Prefrontal Neurons Encode the Association of Paired Visual Stimuli during the Pair-Association Task

    Science.gov (United States)

    Andreau, Jorge Mario; Funahashi, Shintaro

    2011-01-01

    The prefrontal cortex (PFC) is known to contribute to memory processes such as encoding representations into long-term-memory (LTM) and retrieving these representations from LTM. However, the details of the PFC's contribution to LTM processes are not well known. To examine the characteristics of the PFC's contribution to LTM processes, we analyzed…

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

    Science.gov (United States)

    Paneri, Sofia; Gregoriou, Georgia G.

    2017-01-01

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

  3. Adenosine A2A Receptors Control Glutamatergic Synaptic Plasticity in Fast Spiking Interneurons of the Prefrontal Cortex

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    Amber Kerkhofs

    2018-03-01

    Full Text Available Adenosine A2A receptors (A2AR are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While it is reported that A2AR are involved in the control of prefrontal cortex (PFC-dependent behavior such as working memory, reversal learning and effort-based decision making, it is not known whether A2AR control glutamatergic synapse plasticity within the medial PFC (mPFC. To elucidate that, we tested whether A2AR blockade affects long-term plasticity (LTP of excitatory post-synaptic potentials in pyramidal neurons and fast spiking (FS interneurons in layer 5 of the mPFC and of population spikes. Our results show that A2AR are enriched at mPFC synapses, where their blockade reversed the direction of plasticity at excitatory synapses onto layer 5 FS interneurons from LTP to long-term depression, while their blockade had no effect on the induction of LTP at excitatory synapses onto layer 5 pyramidal neurons. At the network level, extracellularly induced LTP of population spikes was reduced by A2AR blockade. The interneuron-specificity of A2AR in controlling glutamatergic synapse LTP may ensure that during periods of high synaptic activity, a proper excitation/inhibition balance is maintained within the mPFC.

  4. Cell and receptor type-specific alterations in markers of GABA neurotransmission in the prefrontal cortex of subjects with schizophrenia.

    Science.gov (United States)

    Lewis, David A; Hashimoto, Takanori; Morris, Harvey M

    2008-10-01

    Impairments in cognitive control, such as those involved in working memory, are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC) in individuals with schizophrenia. This dysfunction appears to result, at least in part, from abnormalities in GABA-mediated neurotransmission. In this paper, we review recent findings indicating that the altered DLPFC circuitry in subjects with schizophrenia reflects changes in the expression of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmission. Specifically, using a combination of methods, we found that subjects with schizophrenia exhibited expression deficits in GABA-related transcripts encoding presynaptic regulators of GABA neurotransmission, neuropeptide markers of specific subpopulations of GABA neurons, and certain subunits of the GABA(A) receptor. In particular, alterations in the expression of the neuropeptide somatostatin suggested that GABA neurotransmission is impaired in the Martinotti subset of GABA neurons that target the dendrites of pyramidal cells. In contrast, none of the GABA-related transcripts assessed to date were altered in the DLPFC of monkeys chronically exposed to antipsychotic medications, suggesting that the effects observed in the human studies reflect the disease process and not its treatment. In concert with previous findings, these data suggest that working memory dysfunction in schizophrenia may be attributable to altered GABA neurotransmission in specific DLPFC microcircuits.

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

    Directory of Open Access Journals (Sweden)

    Sofia Paneri

    2017-09-01

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

  6. Prioritising the relevant information for learning and decision making within orbital and ventromedial prefrontal cortex.

    Science.gov (United States)

    Walton, Mark E; Chau, Bolton K H; Kennerley, Steven W

    2015-02-01

    Our environment and internal states are frequently complex, ambiguous and dynamic, meaning we need to have selection mechanisms to ensure we are basing our decisions on currently relevant information. Here, we review evidence that orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) play conserved, critical but distinct roles in this process. While OFC may use specific sensory associations to enhance task-relevant information, particularly in the context of learning, VMPFC plays a role in ensuring irrelevant information does not impinge on the decision in hand.

  7. Listen, learn, like! Dorsolateral prefrontal cortex involved in the mere exposure effect in music

    DEFF Research Database (Denmark)

    Green, Anders Christian; Bærentsen, Klaus B.; Stødkilde-Jørgensen, Hans

    2012-01-01

    , participants rated liking for each melody and, later, their recognition of them. Participants showed learning effects, better recognising melodies heard more often. Melodies heard most often were most liked, consistent with the mere exposure effect. We found neural activations as a function of previous...... exposure in bilateral dorsolateral prefrontal and inferior parietal cortex, probably reflecting retrieval and working memory-related processes. This was despite the fact that the task during scanning was to judge liking, not recognition, thus suggesting that appreciation of music relies strongly on memory...

  8. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin......-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact...

  9. The Importance of the Lateral Prefrontal Cortex for Strategic Decision Making in the Prisoner's Dilemma.

    Science.gov (United States)

    Soutschek, Alexander; Sauter, Marian; Schubert, Torsten

    2015-12-01

    Previous functional imaging studies investigating the neural basis of strategic decision making in the prisoner's dilemma reported a correlation between cooperative behavior and dorsolateral prefrontal cortex (DLPFC) activity; however, the precise function of the DLPFC in establishing cooperation remains unclear so far. The present study investigated the causal role of the DLPFC in an iterative prisoner's dilemma game with transcranial magnetic stimulation (TMS). We discovered that disrupting the DLPFC with TMS decreased cooperation rates in comparison to control conditions, with this effect being most pronounced when the partner had defected previously. Thus, the current results suggest that the DLPFC contributes to strategic decision making in the prisoner's dilemma game.

  10. Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons

    Science.gov (United States)

    Cheung, Iris; Bharadwaj, Rahul; Chou, Hsin-Jung; Houston, Isaac B.; Peter, Cyril J.; Mitchell, Amanda C.; Yao, Wei-Dong; Myers, Richard H.; Chen, Jiang-fan; Preuss, Todd M.; Rogaev, Evgeny I.; Jensen, Jeffrey D.; Weng, Zhiping; Akbarian, Schahram

    2012-01-01

    Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5–1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans. PMID:23185133

  11. The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

    Science.gov (United States)

    Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

    2017-10-01

    Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.

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

    Directory of Open Access Journals (Sweden)

    Anthony Charles Ruocco

    2016-05-01

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

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

    Science.gov (United States)

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

    2015-08-26

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

  14. Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

  15. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

  19. Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Guillaume Martel

    Full Text Available Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD. Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR. Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction.

  20. Ketamine-Induced Changes in the Signal and Noise of Rule Representation in Working Memory by Lateral Prefrontal Neurons.

    Science.gov (United States)

    Ma, Liya; Skoblenick, Kevin; Seamans, Jeremy K; Everling, Stefan

    2015-08-19

    Working memory dysfunction is an especially debilitating symptom in schizophrenia. The NMDA antagonist ketamine has been successfully used to model working memory deficits in both rodents and nonhuman primates, but how it affects the strength and the consistency of working memory representations remains unclear. Here we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine in a rule-based working memory task. The rule was instructed with a color cue before each delay period and dictated the correct prosaccadic or antisaccadic response to a peripheral stimulus appearing after the delay. We found that acute ketamine injections both weakened the rule signal across all delay periods and amplified the trial-to-trial variance in neural activities (i.e., noise), both within individual neurons and at the ensemble level, resulting in impaired performance. In the minority of postinjection trials when the animals responded correctly, the preservation of the signal strength during the delay periods was predictive of their subsequent success. Our findings suggest that NMDA receptor function may be critical for establishing the optimal signal-to-noise ratio in information representation by ensembles of prefrontal cortex neurons. In schizophrenia patients, working memory deficit is highly debilitating and currently without any efficacious treatment. An improved understanding of the pathophysiology of this symptom may provide critical information to treatment development. The NMDA antagonist ketamine, when injected at a subanesthetic dose, produces working memory deficit and other schizophrenia-like symptoms in humans and other animals. Here we investigated the effects of ketamine on the representation of abstract rules by prefrontal neurons, while macaque monkeys held the rules in working memory before responding accordingly. We found that ketamine weakened the signal

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

    Science.gov (United States)

    Pulvermüller, Friedemann; Garagnani, Max

    2014-08-01

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

  2. The role of the ventromedial prefrontal cortex in purchase intent among older adults

    Directory of Open Access Journals (Sweden)

    Bryan P Koestner

    2016-08-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-12-22

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

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

    Science.gov (United States)

    Koban, Leonie; Pichon, Swann; Vuilleumier, Patrik

    2014-05-01

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

  7. Hope, coping skills, and the prefrontal cortex in alcohol use disorder recovery.

    Science.gov (United States)

    Bradshaw, Spencer D; Shumway, Sterling T; Dsauza, Cynthia M; Morris, Neli; Hayes, Nicholas D

    2017-09-01

    Alcohol use disorders adversely affect individual and societal health. These disorders are a chronic brain disease, and protective factors against relapse should be studied. Prefrontal cortex (PFC) dysfunction is evident in alcohol use disorders, and research that explores recovery of the PFC in alcohol use disorders is needed, specifically in regard to how psychological and behavioral factors can augment medicalized treatments and protect against relapse. For example, hope or a belief that recovery is possible is an important cognitive construct-thought to precede behavioral action-that has been associated with relapse. In this study, associations between healthy coping skills and hope (psychological/behavioral factors) and PFC regional activation in response to alcohol cue exposure were examined. It was also examined whether such associations were unique to alcohol cues. Forty-two participants, 32 males and nine females in recovery from an alcohol use disorder (AUD), were administered a subjective hope and coping in recovery measure. They also viewed alcohol, positive, negative, and neutral cues during functional near-infrared spectroscopy (fNIR) PFC assessment. Levels of healthy coping skills positively correlated with activation in the right dorsomedial prefrontal cortex (DMPFC) in response to alcohol cues. This finding was unique to alcohol cues. The association between coping skills and activation of the right DMPFC in response to alcohol cues may reflect greater action restraint and top-down PFC control processing that may protect against relapse.

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

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    Takehiro Minamoto

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  11. The Role of the Rat Medial Prefrontal Cortex in Adapting to Changes in Instrumental Contingency

    Science.gov (United States)

    Coutureau, Etienne; Esclassan, Frederic; Di Scala, Georges; Marchand, Alain R.

    2012-01-01

    In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies – i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks. PMID:22496747

  12. Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control.

    Science.gov (United States)

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

    2013-03-01

    Functional interactions between limbic regions that process emotions and frontal networks that guide response functions provide a substrate for emotional cues to influence behavior. Stimulation of postsynaptic α₂ adrenoceptors enhances the function of prefrontal regions in these networks. However, the impact of this stimulation on the emotional biasing of behavior has not been established. This study tested the effect of the postsynaptic α₂ adrenoceptor agonist guanfacine on the emotional biasing of response execution and inhibition in prefrontal cortex. Fifteen healthy young adults were scanned twice with functional magnetic resonance imaging while performing a face emotion go/no-go task following counterbalanced administration of single doses of oral guanfacine (1 mg) and placebo in a double-blind, cross-over design. Lower perceptual sensitivity and less response bias for sad faces resulted in fewer correct responses compared to happy and neutral faces but had no effect on correct inhibitions. Guanfacine increased the sensitivity and bias selectively for sad faces, resulting in response accuracy comparable to happy and neutral faces, and reversed the valence-dependent variation in response-related activation in left dorsolateral prefrontal cortex (DLPFC), resulting in enhanced activation for response execution cued by sad faces relative to happy and neutral faces, in line with other frontoparietal regions. These results provide evidence that guanfacine stimulation of postsynaptic α₂ adrenoceptors moderates DLPFC activation associated with the emotional biasing of response execution processes. The findings have implications for the α₂ adrenoceptor agonist treatment of attention-deficit hyperactivity disorder.

  13. Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

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    Nair, Sunila G; Gudelsky, Gary A

    2004-09-15

    The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

  14. Multiple time scales of adaptation in auditory cortex neurons.

    Science.gov (United States)

    Ulanovsky, Nachum; Las, Liora; Farkas, Dina; Nelken, Israel

    2004-11-17

    Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

  15. What might have been? The role of the ventromedial prefrontal cortex and lateral orbitofrontal cortex in counterfactual emotions and choice.

    Science.gov (United States)

    Levens, Sara M; Larsen, Jeff T; Bruss, Joel; Tranel, Daniel; Bechara, Antoine; Mellers, Barbara A

    2014-02-01

    Counterfactual feelings of regret occur when people make comparisons between an actual outcome and a better outcome that would have occurred under a different choice. We investigated the choices of individuals with damage to the ventral medial prefrontal cortex (VMPFC) and the lateral orbital frontal cortex (LOFC) to see whether their emotional responses were sensitive to regret. Participants made choices between gambles, each with monetary outcomes. After every choice, subjects learned the consequences of both gambles and rated their emotional response to the outcome. Normal subjects and lesion control subjects tended to make better choices and reported post-decision emotions that were sensitive to regret comparisons. VMPFC patients tended to make worse choices, and, contrary to our predictions, they reported emotions that were sensitive to regret comparisons. In contrast, LOFC patients made better choices, but reported emotional reactions that were insensitive to regret comparisons. We suggest the VMPFC is involved in the association between choices and anticipated emotions that guide future choices, while the LOFC is involved in experienced emotions that follow choices, emotions that may signal the need for behavioral change. © 2013 Elsevier Ltd. All rights reserved.

  16. The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

    Science.gov (United States)

    Silton, Rebecca Levin; Heller, Wendy; Towers, David N; Engels, Anna S; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

    2010-04-15

    A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model. Copyright 2009 Elsevier Inc. All rights reserved.

  17. Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

    Science.gov (United States)

    Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

    2017-05-23

    Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.

  18. How do auditory cortex neurons represent communication sounds?

    Science.gov (United States)

    Gaucher, Quentin; Huetz, Chloé; Gourévitch, Boris; Laudanski, Jonathan; Occelli, Florian; Edeline, Jean-Marc

    2013-11-01

    A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Adolescent Social Stress Produces an Enduring Activation of the Rat Locus Coeruleus and Alters its Coherence with the Prefrontal Cortex

    Science.gov (United States)

    Zitnik, Gerard A; Curtis, Andrè L; Wood, Susan K; Arner, Jay; Valentino, Rita J

    2016-01-01

    Early life stress is associated with the development of psychiatric disorders. Because the locus coeruleus-norepinephrine (LC-NE) system is a major stress-response system that is implicated in psychopathology, developmental differences in the response of this system to stress may contribute to increased vulnerability. Here LC single unit and network activity were compared between adult and adolescent rats during resident-intruder stress. In some rats, LC and medial prefrontal cortex (mPFC) coherence was quantified. The initial stress tonically activated LC neurons and induced theta oscillations, while simultaneously decreasing LC auditory-evoked responses in both age groups. Stress increased LC-mPFC coherence within the theta range. With repeated exposures, adolescent LC neuronal and network activity remained elevated even in the absence of the stressor and were unresponsive to stressor presentation. In contrast, LC neurons of adult rats exposed to repeated social stress were relatively inhibited in the absence of the stressor and mounted robust responses upon stressor presentation. LC sensory-evoked responses were selectively blunted in adolescent rats exposed to repeated social stress. Finally, repeated stress decreased LC-mPFC coherence in the high frequency range (beta and gamma) while maintaining strong coherence in the theta range, selectively in adolescents. Together, these results suggest that adaptive mechanisms that promote stress recovery and maintain basal activity of the brain norepinephrine system in the absence of stress are not fully developed or are vulnerable stress-induced impairments in adolescence. The resulting sustained activation of the LC-NE system after repeated social stress may adversely impact cognition and future social behavior of adolescents. PMID:26361057

  20. Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex.

    Science.gov (United States)

    Yamamuro, Kazuhiko; Yoshino, Hiroki; Ogawa, Yoichi; Makinodan, Manabu; Toritsuka, Michihiro; Yamashita, Masayuki; Corfas, Gabriel; Kishimoto, Toshifumi

    2018-03-01

    Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    Science.gov (United States)

    Tomasino, Barbara; Fabbro, Franco

    2016-02-01

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

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

    Science.gov (United States)

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

    2015-06-30

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

  3. Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning.

    Science.gov (United States)

    Whitaker, Leslie R; Warren, Brandon L; Venniro, Marco; Harte, Tyler C; McPherson, Kylie B; Beidel, Jennifer; Bossert, Jennifer M; Shaham, Yavin; Bonci, Antonello; Hope, Bruce T

    2017-09-06

    Learned associations between environmental stimuli and rewards drive goal-directed learning and motivated behavior. These memories are thought to be encoded by alterations within specific patterns of sparsely distributed neurons called neuronal ensembles that are activated selectively by reward-predictive stimuli. Here, we use the Fos promoter to identify strongly activated neuronal ensembles in rat prelimbic cortex (PLC) and assess altered intrinsic excitability after 10 d of operant food self-administration training (1 h/d). First, we used the Daun02 inactivation procedure in male FosLacZ-transgenic rats to ablate selectively Fos-expressing PLC neurons that were active during operant food self-administration. Selective ablation of these neurons decreased food seeking. We then used male FosGFP-transgenic rats to assess selective alterations of intrinsic excitability in Fos-expressing neuronal ensembles (FosGFP + ) that were activated during food self-administration and compared these with alterations in less activated non-ensemble neurons (FosGFP - ). Using whole-cell recordings of layer V pyramidal neurons in an ex vivo brain slice preparation, we found that operant self-administration increased excitability of FosGFP + neurons and decreased excitability of FosGFP - neurons. Increased excitability of FosGFP + neurons was driven by increased steady-state input resistance. Decreased excitability of FosGFP - neurons was driven by increased contribution of small-conductance calcium-activated potassium (SK) channels. Injections of the specific SK channel antagonist apamin into PLC increased Fos expression but had no effect on food seeking. Overall, operant learning increased intrinsic excitability of PLC Fos-expressing neuronal ensembles that play a role in food seeking but decreased intrinsic excitability of Fos - non-ensembles. SIGNIFICANCE STATEMENT Prefrontal cortex activity plays a critical role in operant learning, but the underlying cellular mechanisms are

  4. Selective increases of AMPA, NMDA and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics

    Directory of Open Access Journals (Sweden)

    Zhe eJin

    2014-01-01

    Full Text Available Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG, orbitofrontal cortex (OFC, and dorso-lateral prefrontal cortex (DL-PFC samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-ylpropanoic acid receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate receptor subunits GluN1, GluN2A, GluN2C, GluN2D and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011. Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

  5. Neurons in primary motor cortex engaged during action observation.

    Science.gov (United States)

    Dushanova, Juliana; Donoghue, John

    2010-01-01

    Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These 'view' neurons were spatially intermingled with 'do' neurons, which are active only during movement performance. Simultaneously recorded 'view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. 'View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 'view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action.

  6. Relating neuronal firing patterns to functional differentiation of cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Shigeru Shinomoto

    2009-07-01

    Full Text Available It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

  7. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    Science.gov (United States)

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Lateralized Contribution of Prefrontal Cortex in Controlling Task-Irrelevant Information during Verbal and Spatial Working Memory Tasks: rTMS Evidence

    Science.gov (United States)

    Sandrini, Marco; Rossini, Paolo Maria; Miniussi, Carlo

    2008-01-01

    The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs.…

  9. The role of the medial prefrontal cortex in the play fighting of rats.

    Science.gov (United States)

    Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

    2009-12-01

    Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

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

    Science.gov (United States)

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

    2011-07-01

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

  11. Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users.

    Science.gov (United States)

    Hermann, Derik; Sartorius, Alexander; Welzel, Helga; Walter, Sigrid; Skopp, Gisela; Ende, Gabriele; Mann, Karl

    2007-06-01

    Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.

  12. The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-o-methyltransferase genotypes and schizophrenia.

    Science.gov (United States)

    Durstewitz, Daniel; Seamans, Jeremy K

    2008-11-01

    There is now general consensus that at least some of the cognitive deficits in schizophrenia are related to dysfunctions in the prefrontal cortex (PFC) dopamine (DA) system. At the cellular and synaptic level, the effects of DA in PFC via D1- and D2-class receptors are highly complex, often apparently opposing, and hence difficult to understand with regard to their functional implications. Biophysically realistic computational models have provided valuable insights into how the effects of DA on PFC neurons and synaptic currents as measured in vitro link up to the neural network and cognitive levels. They suggest the existence of two discrete dynamical regimes, a D1-dominated state characterized by a high energy barrier among different network patterns that favors robust online maintenance of information and a D2-dominated state characterized by a low energy barrier that is beneficial for flexible and fast switching among representational states. These predictions are consistent with a variety of electrophysiological, neuroimaging, and behavioral results in humans and nonhuman species. Moreover, these biophysically based models predict that imbalanced D1:D2 receptor activation causing extremely low or extremely high energy barriers among activity states could lead to the emergence of cognitive, positive, and negative symptoms observed in schizophrenia. Thus, combined experimental and computational approaches hold the promise of allowing a detailed mechanistic understanding of how DA alters information processing in normal and pathological conditions, thereby potentially providing new routes for the development of pharmacological treatments for schizophrenia.

  13. Synapse density and dendritic complexity are reduced in the prefrontal cortex following seven days of forced abstinence from cocaine self-administration.

    Directory of Open Access Journals (Sweden)

    Khampaseuth Rasakham

    Full Text Available Chronic cocaine exposure in both human addicts and in rodent models of addiction reduces prefrontal cortical activity, which subsequently dysregulates reward processing and higher order executive function. The net effect of this impaired gating of behavior is enhanced vulnerability to relapse. Previously we have shown that cocaine-induced increases in brain-derived neurotrophic factor (BDNF expression in the medial prefrontal cortex (PFC is a neuroadaptive mechanism that blunts the reinforcing efficacy of cocaine. As BDNF is known to affect neuronal survival and synaptic plasticity, we tested the hypothesis that abstinence from cocaine self-administration would lead to alterations in neuronal morphology and synaptic density in the PFC. Using a novel technique, array tomography and Golgi staining, morphological changes in the rat PFC were analyzed following 14 days of cocaine self-administration and 7 days of forced abstinence. Our results indicate that overall dendritic branching and total synaptic density are significantly reduced in the rat PFC. In contrast, the density of thin dendritic spines are significantly increased on layer V pyramidal neurons of the PFC. These findings indicate that dynamic structural changes occur during cocaine abstinence that may contribute to the observed hypo-activity of the PFC in cocaine-addicted individuals.

  14. Neuronal representation of individual heroin choices in the orbitofrontal cortex.

    Science.gov (United States)

    Guillem, Karine; Brenot, Viridiana; Durand, Audrey; Ahmed, Serge H

    2018-05-01

    Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice. © 2017 Society for the Study of Addiction.

  15. INCREASES IN FUNCTIONAL CONNECTIVITY BETWEEN PREFRONTAL CORTEX AND STRIATUM DURING CATEGORY LEARNING

    Science.gov (United States)

    Antzoulatos, Evan G.; Miller, Earl K.

    2014-01-01

    SUMMARY Functional connectivity between the prefrontal cortex (PFC) and striatum (STR) is thought critical for cognition, and has been linked to conditions like autism and schizophrenia. We recorded from multiple electrodes in PFC and STR while monkeys acquired new categories. Category learning was accompanied by an increase in beta-band synchronization of LFPs between, but not within, the PFC and STR. After learning, different pairs of PFC-STR electrodes showed stronger synchrony for one or the other category, suggesting category-specific functional circuits. This category-specific synchrony was also seen between PFC spikes and STR LFPs, but not the reverse, reflecting the direct monosynaptic connections from the PFC to STR. However, causal connectivity analyses suggested that the polysynaptic connections from STR to the PFC exerted a stronger overall influence. This supports models positing that the basal ganglia “train” the PFC. Category learning may depend on the formation of functional circuits between the PFC and STR. PMID:24930701

  16. Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.

    Science.gov (United States)

    Gonzalez, Maria Carolina; Villar, Maria Eugenia; Igaz, Lionel M; Viola, Haydée; Medina, Jorge H

    2015-12-01

    The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The amygdala and ventromedial prefrontal cortex: functional contributions and dysfunction in psychopathy.

    Science.gov (United States)

    Blair, R J R

    2008-08-12

    The current paper examines the functional contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) and the evidence that the functioning of these systems is compromised in individuals with psychopathy. The amygdala is critical for the formation of stimulus-reinforcement associations, both punishment and reward based, and the processing of emotional expressions. vmPFC is critical for the representation of reinforcement expectancies and, owing to this, decision making. Neuropsychological and neuroimaging data from individuals with psychopathy are examined. It is concluded that these critical functions of the amygdala and vmPFC, and their interaction, are compromised in individuals with the disorder. It is argued that these impairments lead to the development of psychopathy.

  18. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    Science.gov (United States)

    Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

    2014-01-01

    Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

  19. Neuroanatomical Substrates of Rodent Social Behavior: The Medial Prefrontal Cortex and Its Projection Patterns

    Science.gov (United States)

    Ko, Jaewon

    2017-01-01

    Social behavior encompasses a number of distinctive and complex constructs that form the core elements of human imitative culture, mainly represented as either affiliative or antagonistic interactions with conspecifics. Traditionally considered in the realm of psychology, social behavior research has benefited from recent advancements in neuroscience that have accelerated identification of the neural systems, circuits, causative genes and molecular mechanisms that underlie distinct social cognitive traits. In this review article, I summarize recent findings regarding the neuroanatomical substrates of key social behaviors, focusing on results from experiments conducted in rodent models. In particular, I will review the role of the medial prefrontal cortex (mPFC) and downstream subcortical structures in controlling social behavior, and discuss pertinent future research perspectives. PMID:28659766

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

    Geday, Jacob; Gjedde, Albert

    2008-01-01

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

  2. Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex.

    Science.gov (United States)

    Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

    2016-10-25

    Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life.

  3. Dorsolateral prefrontal cortex, working memory and episodic memory processes: insight through transcranial magnetic stimulation techniques

    Institute of Scientific and Technical Information of China (English)

    Michela Balconi

    2013-01-01

    The ability to recall and recognize facts we experienced in the past is based on a complex mechanism in which several cerebral regions are implicated.Neuroimaging and lesion studies agree in identifying the frontal lobe as a crucial structure for memory processes,and in particular for working memory and episodic memory and their relationships.Furthermore,with the introduction of transcranial magnetic stimulation (TMS) a new way was proposed to investigate the relationships between brain correlates,memory functions and behavior.The aim of this review is to present the main findings that have emerged from experiments which used the TMS technique for memory analysis.They mainly focused on the role of the dorsolateral prefrontal cortex in memory process.Furthermore,we present state-of-the-art evidence supporting a possible use of TMS in the clinic.Specifically we focus on the treatment of memory deficits in depression and anxiety disorders.

  4. Listen, Learn, Like! Dorsolateral Prefrontal Cortex Involved in the Mere Exposure Effect in Music

    Directory of Open Access Journals (Sweden)

    Anders C. Green

    2012-01-01

    Full Text Available We used functional magnetic resonance imaging to investigate the neural basis of the mere exposure effect in music listening, which links previous exposure to liking. Prior to scanning, participants underwent a learning phase, where exposure to melodies was systematically varied. During scanning, participants rated liking for each melody and, later, their recognition of them. Participants showed learning effects, better recognising melodies heard more often. Melodies heard most often were most liked, consistent with the mere exposure effect. We found neural activations as a function of previous exposure in bilateral dorsolateral prefrontal and inferior parietal cortex, probably reflecting retrieval and working memory-related processes. This was despite the fact that the task during scanning was to judge liking, not recognition, thus suggesting that appreciation of music relies strongly on memory processes. Subjective liking per se caused differential activation in the left hemisphere, of the anterior insula, the caudate nucleus, and the putamen.

  5. Listen, learn, like! Dorsolateral prefrontal cortex involved in the mere exposure effect in music.

    Science.gov (United States)

    Green, Anders C; Bærentsen, Klaus B; Stødkilde-Jørgensen, Hans; Roepstorff, Andreas; Vuust, Peter

    2012-01-01

    We used functional magnetic resonance imaging to investigate the neural basis of the mere exposure effect in music listening, which links previous exposure to liking. Prior to scanning, participants underwent a learning phase, where exposure to melodies was systematically varied. During scanning, participants rated liking for each melody and, later, their recognition of them. Participants showed learning effects, better recognising melodies heard more often. Melodies heard most often were most liked, consistent with the mere exposure effect. We found neural activations as a function of previous exposure in bilateral dorsolateral prefrontal and inferior parietal cortex, probably reflecting retrieval and working memory-related processes. This was despite the fact that the task during scanning was to judge liking, not recognition, thus suggesting that appreciation of music relies strongly on memory processes. Subjective liking per se caused differential activation in the left hemisphere, of the anterior insula, the caudate nucleus, and the putamen.

  6. Dissecting contributions of prefrontal cortex and fusiform face area to face working memory.

    Science.gov (United States)

    Druzgal, T Jason; D'Esposito, Mark

    2003-08-15

    Interactions between prefrontal cortex (PFC) and stimulus-specific visual cortical association areas are hypothesized to mediate visual working memory in behaving monkeys. To clarify the roles for homologous regions in humans, event-related fMRI was used to assess neural activity in PFC and fusiform face area (FFA) of subjects performing a delay-recognition task for faces. In both PFC and FFA, activity increased parametrically with memory load during encoding and maintenance of face stimuli, despite quantitative differences in the magnitude of activation. Moreover, timing differences in PFC and FFA activation during memory encoding and retrieval implied a context dependence in the flow of neural information. These results support existing neurophysiological models of visual working memory developed in the nonhuman primate.

  7. Neonatal isolation augments social dominance by altering actin dynamics in the medial prefrontal cortex

    Science.gov (United States)

    Tada, Hirobumi; Miyazaki, Tomoyuki; Takemoto, Kiwamu; Takase, Kenkichi; Jitsuki, Susumu; Nakajima, Waki; Koide, Mayu; Yamamoto, Naoko; Komiya, Kasane; Suyama, Kumiko; Sano, Akane; Taguchi, Akiko; Takahashi, Takuya

    2016-01-01

    Social separation early in life can lead to the development of impaired interpersonal relationships and profound social disorders. However, the underlying cellular and molecular mechanisms involved are largely unknown. Here, we found that isolation of neonatal rats induced glucocorticoid-dependent social dominance over nonisolated control rats in juveniles from the same litter. Furthermore, neonatal isolation inactivated the actin-depolymerizing factor (ADF)/cofilin in the juvenile medial prefrontal cortex (mPFC). Isolation-induced inactivation of ADF/cofilin increased stable actin fractions at dendritic spines in the juvenile mPFC, decreasing glutamate synaptic AMPA receptors. Expression of constitutively active ADF/cofilin in the mPFC rescued the effect of isolation on social dominance. Thus, neonatal isolation affects spines in the mPFC by reducing actin dynamics, leading to altered social behavior later in life. PMID:27791080

  8. Negative emotion modulates prefrontal cortex activity during a working memory task: A NIRS study

    Directory of Open Access Journals (Sweden)

    Sachiyo eOzawa

    2014-02-01

    Full Text Available This study investigated the neural processing underlying the cognitive control of emotions induced by the presentation of task-irrelevant emotional pictures before a working memory task. Previous studies have suggested that the cognitive control of emotion involves the prefrontal regions. Therefore, we measured the hemodynamic responses that occurred in the prefrontal region with a 16-channel near-infrared spectroscopy (NIRS system. In our experiment, participants observed two negative or two neutral pictures in succession immediately before a 1-back or 3-back task. Pictures were selected from the International Affective Picture System. We measured the changes in the concentration of oxygenated hemoglobin (oxyHb during picture presentation and during the n-back task. The emotional valence of the picture affected the oxyHb changes in anterior parts of the medial prefrontal cortex (located in the left and right superior frontal gyrus and left inferior frontal gyrus during the n-back task; the oxyHb changes during the task were significantly greater following negative rather than neutral stimulation. As indicated in a number of previous studies, and the time courses of the oxyHb changes in our study, activation in these locations is possibly led by cognitive control of emotion, though we cannot deny it may simply be emotional responses. There were no effects of emotion on oxyHb changes during picture presentation or on n-back task performance. Although further studies are necessary to confirm this interpretation, our findings suggest that NIRS can be used to investigate neural processing during emotional control.

  9. Comparison of Hemodynamic Responses in the Prefrontal Cortex According to Differences in Self-Efficacy.

    Science.gov (United States)

    Hirao, Kazuki

    2017-07-01

    Although self-efficacy has been used extensively in the field of nursing (e.g., as an outcome measure of nursing interventions), its underlying nature is poorly understood. Investigation of the relationship between self-efficacy and brain activation will help explain the fundamental nature of self-efficacy. In this study, we compared prefrontal activation measured with near-infrared spectroscopy (NIRS) across 89 undergraduate students categorized into three groups based on their General Self-Efficacy Scale scores: low self-efficacy ( n = 59), moderate self-efficacy ( n = 17), and high self-efficacy ( n = 13). Changes in the hemoglobin levels of the prefrontal cortex (PFC) during a verbal fluency task were assessed using two-channel NIRS. Significant differences in the oxygenated hemoglobin (oxy-Hb) level of the left PFC (LPFC) were observed via analysis of variance. Post hoc Tukey's test showed a significant difference only between low self-efficacy and moderate self-efficacy groups. We found a medium between-group effect size in the moderate self-efficacy group versus the low self-efficacy group for the changes in oxy-Hb levels of the LPFC ( d = .78; 95% confidence interval for effect size [0.22, 1.33]). No significant between-group differences were observed with respect to changes in the oxy-Hb in the right PFC. The results indicate less left prefrontal activation in the low self-efficacy group than in the moderate self-efficacy group. These findings provide evidence to support the fundamental nature of self-efficacy.

  10. Golgi Analysis of Neuron Morphology in the Presumptive Somatosensory Cortex and Visual Cortex of the Florida Manatee (Trichechus manatus latirostris).

    Science.gov (United States)

    Reyes, Laura D; Harland, Tessa; Reep, Roger L; Sherwood, Chet C; Jacobs, Bob

    2016-01-01

    The current study investigates neuron morphology in presumptive primary somatosensory (S1) and primary visual (V1) cortices of the Florida manatee (Trichechus manatus latirostris) as revealed by Golgi impregnation. Sirenians, including manatees, have an aquatic lifestyle, a large body size, and a relatively large lissencephalic brain. The present study examines neuron morphology in 3 cortical areas: in S1, dorsolateral cortex area 1 (DL1) and cluster cortex area 2 (CL2) and in V1, dorsolateral cortex area 4 (DL4). Neurons exhibited a variety of morphological types, with pyramidal neurons being the most common. The large variety of neuron types present in the manatee cortex was comparable to that seen in other eutherian mammals, except for rodents and primates, where pyramid-shaped neurons predominate. A comparison between pyramidal neurons in S1 and V1 indicated relatively greater dendritic branching in S1. Across all 3 areas, the dendritic arborization pattern of pyramidal neurons was also similar to that observed previously in the afrotherian rock hyrax, cetartiodactyls, opossums, and echidnas but did not resemble the widely bifurcated dendrites seen in the large-brained African elephant. Despite adaptations for an aquatic environment, manatees did not share specific neuron types such as tritufted and star-like neurons that have been found in cetaceans. Manatees exhibit an evolutionarily primitive pattern of cortical neuron morphology shared with most other mammals and do not appear to have neuronal specializations for an aquatic niche. © 2016 S. Karger AG, Basel.

  11. Infralimbic Prefrontal Cortex Interacts with Nucleus Accumbens Shell to Unmask Expression of Outcome-Selective Pavlovianto- Instrumental Transfer

    Science.gov (United States)

    Keistler, Colby; Barker, Jacqueline M.; Taylor, Jane R.

    2015-01-01

    Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context…

  12. The release of noradrenaline in the locus coeruleus and prefrontal cortex studied with dual-probe microdialysis

    NARCIS (Netherlands)

    Pudovkina, O; Kawahara, Y; de Vries, J.B; Westerink, B.H.C.

    2001-01-01

    The present study was undertaken to investigate and compare the properties of noradrenaline release in the locus coeruleus (LC) and prefrontal cortex (PFC). For that aim the dual-probe microdialysis technique was applied for simultaneous detection of noradrenaline levels in the LC and PFC in

  13. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  14. Loss of lateral prefrontal cortex control in food-directed attention and goal-directed food choice in obesity

    NARCIS (Netherlands)

    Janssen, Lieneke K.; Duif, Iris; Loon, van Ilke; Wegman, Joost; Vries, de Jeanne H.M.; Cools, Roshan; Aarts, Esther

    2017-01-01

    Loss of lateral prefrontal cortex (lPFC)-mediated attentional control may explain the automatic tendency to eat in the face of food. Here, we investigate the neurocognitive mechanism underlying attentional bias to food words and its association with obesity using a food Stroop task. We tested 76

  15. Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias

    NARCIS (Netherlands)

    Ott, D.V.M.; Ullsperger, M.; Jocham, G.; Neumann, J.; Klein, T.A.

    2011-01-01

    The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of

  16. Blockade of IP[subscript 3]-Mediated SK Channel Signaling in the Rat Medial Prefrontal Cortex Improves Spatial Working Memory

    Science.gov (United States)

    Brennan, Avis R.; Dolinsky, Beth; Vu, Mai-Anh T.; Stanley, Marion; Yeckel, Mark F.; Arnsten, Amy F. T.

    2008-01-01

    Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP[subscript 3]-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP[subscript 3] receptor (IP[subscript…

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

    Science.gov (United States)

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

    2005-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Béatrice Garcin

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

  19. Involvement of the Ventrolateral Prefrontal Cortex in Learning Others' Bad Reputations and Indelible Distrust.

    Science.gov (United States)

    Suzuki, Atsunobu; Ito, Yuichi; Kiyama, Sachiko; Kunimi, Mitsunobu; Ohira, Hideki; Kawaguchi, Jun; Tanabe, Hiroki C; Nakai, Toshiharu

    2016-01-01

    A bad reputation can persistently affect judgments of an individual even when it turns out to be invalid and ought to be disregarded. Such indelible distrust may reflect that the negative evaluation elicited by a bad reputation transfers to a person. Consequently, the person him/herself may come to activate this negative evaluation irrespective of the accuracy of the reputation. If this theoretical model is correct, an evaluation-related brain region will be activated when witnessing a person whose bad reputation one has learned about, regardless of whether the reputation is deemed valid or not. Here, we tested this neural hypothesis with functional magnetic resonance imaging (fMRI). Participants memorized faces paired with either a good or a bad reputation. Next, they viewed the faces alone and inferred whether each person was likely to cooperate, first while retrieving the reputations, and then while trying to disregard them as false. A region of the left ventrolateral prefrontal cortex (vlPFC), which may be involved in negative evaluation, was activated by faces previously paired with bad reputations, irrespective of whether participants attempted to retrieve or disregard these reputations. Furthermore, participants showing greater activity of the left ventrolateral prefrontal region in response to the faces with bad reputations were more likely to infer that these individuals would not cooperate. Thus, once associated with a bad reputation, a person may elicit evaluation-related brain responses on their own, thereby evoking distrust independently of their reputation.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Science.gov (United States)

    Cheng, Gordon L F; Lee, Tatia M C

    2016-01-01

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

  2. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    Science.gov (United States)

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  3. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    Directory of Open Access Journals (Sweden)

    Laura eFerreri

    2013-11-01

    Full Text Available Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC. 22 healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  4. Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.

    Directory of Open Access Journals (Sweden)

    Adolfo Sequeira

    Full Text Available Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0 in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides, the anterior cingulate cortex (ACC: 6NS, 9S and the nucleus accumbens (NAcc: 8NS, 13S. ANCOVA was used to control for age, gender, pH and RNA degradation, with P ≤ 0.01 and fold change ± 1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A and three were down-regulated in the NAcc (MT1F, MT1G, MT1H. Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

  5. Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.

    Science.gov (United States)

    Sequeira, Adolfo; Morgan, Ling; Walsh, David M; Cartagena, Preston M; Choudary, Prabhakara; Li, Jun; Schatzberg, Alan F; Watson, Stanley J; Akil, Huda; Myers, Richard M; Jones, Edward G; Bunney, William E; Vawter, Marquis P

    2012-01-01

    Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P ≤ 0.01 and fold change ± 1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

  6. Theory of mind difficulties in patients with alcohol dependence: beyond the prefrontal cortex dysfunction hypothesis.

    Science.gov (United States)

    Maurage, François; de Timary, Philippe; Tecco, Juan Martin; Lechantre, Stéphane; Samson, Dana

    2015-06-01

    Previous studies have shown that alcohol-dependent (AD) individuals have difficulties inferring other people's emotion, understanding humor, and detecting a faux pas. This study aimed at further understanding the nature of such "Theory of Mind" (ToM) difficulties. A total of 34 recently detoxified AD and 34 paired controls were compared based on 2 nonverbal and video-based false belief tasks. These tasks were designed to identify 3 different types of deficits: (i) a deficit in dealing with the general task demands, (ii) a selective deficit in self-perspective inhibition, and (iii) a deficit in tracking the other person's mental state. (i) and (ii) are compatible with the hypothesis of a prefrontal cortex dysfunction being at the origin of AD individuals' social difficulties, while (iii) would suggest the possible contribution of a dysfunction of the temporo-parietal junction in explaining the social difficulties. Group analyses highlighted that AD individuals performed worse on the 2 false belief tasks than controls. Individual analyses showed, however, that just under half of the AD individuals were impaired compared to controls. Moreover, most of the AD individuals who were impaired showed a deficit in tracking the other person's belief. This deficit was linked to disease-related factors such as illness duration, average alcohol consumption, and craving but not to general reasoning abilities, depression, anxiety, or demographic variables. Just under half of the AD individuals tested showed a ToM deficit, and in most cases, the deficit concerned the tracking of other people's mental states. Such a type of deficit has previously been associated with lesions to the temporo-parietal brain areas, indicating that a prefrontal cortex dysfunction may not be the sole origin of the social cognition deficits observed in alcohol dependence. Copyright © 2015 by the Research Society on Alcoholism.

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

    Science.gov (United States)

    Egner, Tobias

    2013-01-01

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

  8. Prefrontal Cortex Structure Predicts Training-Induced Improvements in Multitasking Performance.

    Science.gov (United States)

    Verghese, Ashika; Garner, K G; Mattingley, Jason B; Dux, Paul E

    2016-03-02

    The ability to perform multiple, concurrent tasks efficiently is a much-desired cognitive skill, but one that remains elusive due to the brain's inherent information-processing limitations. Multitasking performance can, however, be greatly improved through cognitive training (Van Selst et al., 1999, Dux et al., 2009). Previous studies have examined how patterns of brain activity change following training (for review, see Kelly and Garavan, 2005). Here, in a large-scale human behavioral and imaging study of 100 healthy adults, we tested whether multitasking training benefits, assessed using a standard dual-task paradigm, are associated with variability in brain structure. We found that the volume of the rostral part of the left dorsolateral prefrontal cortex (DLPFC) predicted an individual's response to training. Critically, this association was observed exclusively in a task-specific training group, and not in an active-training control group. Our findings reveal a link between DLPFC structure and an individual's propensity to gain from training on a task that taps the limits of cognitive control. Cognitive "brain" training is a rapidly growing, multibillion dollar industry (Hayden, 2012) that has been touted as the panacea for a variety of disorders that result in cognitive decline. A key process targeted by such training is "cognitive control." Here, we combined an established cognitive control measure, multitasking ability, with structural brain imaging in a sample of 100 participants. Our goal was to determine whether individual differences in brain structure predict the extent to which people derive measurable benefits from a cognitive training regime. Ours is the first study to identify a structural brain marker-volume of left hemisphere dorsolateral prefrontal cortex-associated with the magnitude of multitasking performance benefits induced by training at an individual level. Copyright © 2016 the authors 0270-6474/16/362638-08$15.00/0.

  9. Delayed enhancement of multitasking performance: Effects of anodal transcranial direct current stimulation on the prefrontal cortex.

    Science.gov (United States)

    Hsu, Wan-Yu; Zanto, Theodore P; Anguera, Joaquin A; Lin, Yung-Yang; Gazzaley, Adam

    2015-08-01

    The dorsolateral prefrontal cortex (DLPFC) has been proposed to play an important role in neural processes that underlie multitasking performance. However, this claim is underexplored in terms of direct causal evidence. The current study aimed to delineate the causal involvement of the DLPFC during multitasking by modulating neural activity with transcranial direct current stimulation (tDCS) prior to engagement in a demanding multitasking paradigm. The study is a single-blind, crossover, sham-controlled experiment. Anodal tDCS or sham tDCS was applied over left DLPFC in forty-one healthy young adults (aged 18-35 years) immediately before they engaged in a 3-D video game designed to assess multitasking performance. Participants were separated into three subgroups: real-sham (i.e., real tDCS in the first session, followed by sham tDCS in the second session 1 h later), sham-real (sham tDCS first session, real tDCS second session), and sham-sham (sham tDCS in both sessions). The real-sham group showed enhanced multitasking performance and decreased multitasking cost during the second session, compared to first session, suggesting delayed cognitive benefits of tDCS. Interestingly, performance benefits were observed only for multitasking and not on a single-task version of the game. No significant changes were found between the first and second sessions for either the sham-real or the sham-sham groups. These results suggest a causal role of left prefrontal cortex in facilitating the simultaneous performance of more than one task, or multitasking. Moreover, these findings reveal that anodal tDCS may have delayed benefits that reflect an enhanced rate of learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Guanfacine potentiates the activation of prefrontal cortex evoked by warning signals.

    Science.gov (United States)

    Clerkin, Suzanne M; Schulz, Kurt P; Halperin, Jeffrey M; Newcorn, Jeffrey H; Ivanov, Iliyan; Tang, Cheuk Y; Fan, Jin

    2009-08-15

    Warning signals evoke an alert state of readiness that prepares for a rapid response by priming a thalamo-frontal-striatal network that includes the dorsolateral prefrontal cortex (DLPFC). Animal models indicate that noradrenergic input is essential for this stimulus-driven activation of DLPFC, but the precise mechanisms involved have not been determined. We tested the role that postsynaptic alpha(2A) adrenoceptors play in the activation of DLPFC evoked by warning cues using a placebo-controlled challenge with the alpha(2A) agonist guanfacine. Sixteen healthy young adults were scanned twice with event-related functional magnetic resonance imaging (fMRI), while performing a simple cued reaction time (RT) task following administration of a single dose of oral guanfacine (1 mg) and placebo in counterbalanced order. The RT task temporally segregates the neural effects of warning cues and motor responses and minimizes mnemonic demands. Warning cues produced a marked reduction in RT accompanied by significant activation in a distributed thalamo-frontal-striatal network, including bilateral DLPFC. Guanfacine selectively increased the cue-evoked activation of the left DLPFC and right anterior cerebellum, although this increase was not accompanied by further reductions in RT. The effects of guanfacine on DLPFC activation were specifically associated with the warning cue and were not seen for visual- or target-related activation. Guanfacine produced marked increases in the cue-evoked activation of DLPFC that correspond to the well-described actions of postsynaptic alpha(2) adrenoceptor stimulation. The current procedures provide an opportunity to test postsynaptic alpha(2A) adrenoceptor function in the prefrontal cortex in the pathophysiology of several psychiatric disorders.

  11. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation.

    Science.gov (United States)

    Ji, Hua; Xu, Linhao; Wang, Zheng; Fan, Xinli; Wu, Lihui

    2018-03-01

    Glyphosate is the active ingredient in numerous herbicide formulations. The role of glyphosate in neurotoxicity has been reported in human and animal models. However, the detailed mechanism of the role of glyphosate in neuronal development remains unknown. Recently, several studies have reported evidence linking neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The current group previously identified microRNAs (miRNAs) that are associated with the etiology of NDDs, but their expression levels in the developing brain following glyphosate exposure have not been characterized. In the present study, miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28 postnatal day mouse offspring following glyphosate exposure during pregnancy and lactation. An miRNA microarray detected 55 upregulated and 19 downregulated miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were further evaluated by quantitative polymerase chain reaction (PCR). A total of 11 targets of these selected deregulated miRNAs were analyzed using bioinformatics. Gene Ontology (GO) terms associated with the relevant miRNAs included neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are involved in the Wnt and Notch signaling pathways, which are closely associated with neural development. PCR arrays for the mouse Wnt and Notch signaling pathways were used to validate the effects of glyphosate on the expression pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated in the PFC of mice offspring following glyphosate exposure during pregnancy and lactation. These results indicated abnormalities of the Wnt/β-catenin and Notch pathways. These findings may be of particular interest for understanding the mechanism of glyphosate-induced neurotoxicity, as

  13. Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging.

    Science.gov (United States)

    Primiani, Christopher T; Ryan, Veronica H; Rao, Jagadeesh S; Cam, Margaret C; Ahn, Kwangmi; Modi, Hiren R; Rapoport, Stanley I

    2014-01-01

    Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes. Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks that operate

  14. Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Christopher T Primiani

    Full Text Available Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases.Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades.We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains and Aging (22 to 78 years, 144 brains intervals, in transcription levels of 39 genes.Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1.Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks

  15. Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

    Science.gov (United States)

    Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Cam, Margaret C.; Ahn, Kwangmi; Modi, Hiren R.; Rapoport, Stanley I.

    2014-01-01

    Background Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Hypothesis Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. Methods We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes. Results Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. Conclusions Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable

  16. Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats.

    Science.gov (United States)

    Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M; Leuner, Benedetta

    2014-07-01

    The neuropeptide oxytocin (OT) is anxiolytic in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, female rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Andrea M Allan

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

  18. Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal Cortex and Mediodorsal Thalamus

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    Zakaria Ouhaz

    2018-02-01

    Full Text Available The mediodorsal nucleus of the thalamus (MD has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making because of its significant interconnectivity with the prefrontal cortex (PFC. Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move, the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction

  19. Medial prefrontal cortex and the adaptive regulation of reinforcement learning parameters.

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    Khamassi, Mehdi; Enel, Pierre; Dominey, Peter Ford; Procyk, Emmanuel

    2013-01-01

    Converging evidence suggest that the medial prefrontal cortex (MPFC) is involved in feedback categorization, performance monitoring, and task monitoring, and may contribute to the online regulation of reinforcement learning (RL) parameters that would affect decision-making processes in the lateral prefrontal cortex (LPFC). Previous neurophysiological experiments have shown MPFC activities encoding error likelihood, uncertainty, reward volatility, as well as neural responses categorizing different types of feedback, for instance, distinguishing between choice errors and execution errors. Rushworth and colleagues have proposed that the involvement of MPFC in tracking the volatility of the task could contribute to the regulation of one of RL parameters called the learning rate. We extend this hypothesis by proposing that MPFC could contribute to the regulation of other RL parameters such as the exploration rate and default action values in case of task shifts. Here, we analyze the sensitivity to RL parameters of behavioral performance in two monkey decision-making tasks, one with a deterministic reward schedule and the other with a stochastic one. We show that there exist optimal parameter values specific to each of these tasks, that need to be found for optimal performance and that are usually hand-tuned in computational models. In contrast, automatic online regulation of these parameters using some heuristics can help producing a good, although non-optimal, behavioral performance in each task. We finally describe our computational model of MPFC-LPFC interaction used for online regulation of the exploration rate and its application to a human-robot interaction scenario. There, unexpected uncertainties are produced by the human introducing cued task changes or by cheating. The model enables the robot to autonomously learn to reset exploration in response to such uncertain cues and events. The combined results provide concrete evidence specifying how prefrontal

  20. The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

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    Di Marzo Vincenzo

    2011-01-01

    Full Text Available Abstract Background Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1 and the catabolic enzyme fatty acid amide hydrolase (FAAH in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL cortex in neuropathic rats. Results The effect of N-arachidonoyl-serotonin (AA-5-HT, a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion These data suggest a possible involvement of endovanilloids in the cortical

  1. Functional connectivity with ventromedial prefrontal cortex reflects subjective value for social rewards.

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    Smith, David V; Clithero, John A; Boltuck, Sarah E; Huettel, Scott A

    2014-12-01

    According to many studies, the ventromedial prefrontal cortex (VMPFC) encodes the subjective value of disparate rewards on a common scale. Yet, a host of other reward factors-likely represented outside of VMPFC-must be integrated to construct such signals for valuation. Using functional magnetic resonance imaging (fMRI), we tested whether the interactions between posterior VMPFC and functionally connected brain regions predict subjective value. During fMRI scanning, participants rated the attractiveness of unfamiliar faces. We found that activation in dorsal anterior cingulate cortex, anterior VMPFC and caudate increased with higher attractiveness ratings. Using data from a post-scan task in which participants spent money to view attractive faces, we quantified each individual's subjective value for attractiveness. We found that connectivity between posterior VMPFC and regions frequently modulated by social information-including the temporal-parietal junction (TPJ) and middle temporal gyrus-was correlated with individual differences in subjective value. Crucially, these additional regions explained unique variation in subjective value beyond that extracted from value regions alone. These findings indicate not only that posterior VMPFC interacts with additional brain regions during valuation, but also that these additional regions carry information employed to construct the subjective value for social reward. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Normal Metabolic Levels in Prefrontal Cortex in Euthymic Bipolar I Patients with and without Suicide Attempts

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    Marlos Vasconcelos Rocha

    2015-01-01

    Full Text Available Introduction/Objective. Evidence suggests that the prefrontal cortex has been implicated in the pathophysiology of bipolar disorder (BD, but few neurochemical studies have evaluated this region in bipolar patients and there is no information from BD suicide attempters using Proton Magnetic Resonance Spectroscopy (H+MRS. The objective was to evaluate the metabolic function of the medial orbital frontal cortex in euthymic BD type I suicide and nonsuicide attempters compared to healthy subjects by H+MRS. Methods. 40 euthymic bipolar I outpatients, 19 without and 21 with history of suicide attempt, and 22 healthy subjects were interviewed using the Structured Clinical Interview with the DSM-IV axis I, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Barratt Impulsiveness Scale-11 and underwent H+MRS. Results. We did not find any metabolic abnormality in medial orbital frontal regions of suicide and nonsuicide BD patients and BD patients as a group compared to healthy subjects. Conclusions. The combined chronic use of psychotropic drugs with neuroprotective or neurotrophic effects leading to a euthymic state for longer periods of time may improve neurometabolic function, at least measured by H+MRS, even in suicide attempters. Besides, these results may implicate mood dependent alterations in brain metabolic activity. However, more studies with larger sample sizes of this heterogeneous disorder are warranted to clarify these data.

  3. Reversible online control of habitual behavior by optogenetic perturbation of medial prefrontal cortex

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    Smith, Kyle S.; Virkud, Arti; Deisseroth, Karl; Graybiel, Ann M.

    2012-01-01

    Habits tend to form slowly but, once formed, can have great stability. We probed these temporal characteristics of habitual behaviors by intervening optogenetically in forebrain habit circuits as rats performed well-ingrained habitual runs in a T-maze. We trained rats to perform a maze habit, confirmed the habitual behavior by devaluation tests, and then, during the maze runs (ca. 3 s), we disrupted population activity in a small region in the medial prefrontal cortex, the infralimbic cortex. In accordance with evidence that this region is necessary for the expression of habits, we found that this cortical disruption blocked habitual behavior. Notably, however, this blockade of habitual performance occurred on line, within an average of three trials (ca. 9 s of inhibition), and as soon as during the first trial (habit, and, simultaneously, the more recently acquired habit was blocked. These online changes occurred within an average of two trials (ca. 6 s of infralimbic inhibition). Measured changes in generalized performance ability and motivation to consume reward were unaffected. This immediate toggling between breaking old habits and returning to them demonstrates that even semiautomatic behaviors are under cortical control and that this control occurs online, second by second. These temporal characteristics define a framework for uncovering cellular transitions between fixed and flexible behaviors, and corresponding disturbances in pathologies. PMID:23112197

  4. An increase in tobacco craving is associated with enhanced medial prefrontal cortex network coupling.

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    Amy C Janes

    Full Text Available Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC network, which also included the subgenual anterior cingulate cortex (sgACC extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving.

  5. Anticipation of a mentally effortful task recruits Dorsolateral Prefrontal Cortex: An fNIRS validation study.

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    Vassena, Eliana; Gerrits, Robin; Demanet, Jelle; Verguts, Tom; Siugzdaite, Roma

    2018-04-26

    Preparing for a mentally demanding task calls upon cognitive and motivational resources. The underlying neural implementation of these mechanisms is receiving growing attention because of its implications for professional, social, and medical contexts. While several fMRI studies converge in assigning a crucial role to a cortico-subcortical network including Anterior Cigulate Cortex (ACC) and striatum, the involvement of Dorsolateral Prefrontal Cortex (DLPFC) during mental effort anticipation has yet to be replicated. This study was designed to target DLPFC contribution to anticipation of a difficult task using functional Near Infrared Spectroscopy (fNIRS), as a more cost-effective tool measuring cortical hemodynamics. We adapted a validated mental effort task, where participants performed easy and difficult mental calculation, and measured DLPFC activity during the anticipation phase. As hypothesized, DLPFC activity increased during anticipation of a hard task as compared to an easy task. Besides replicating previous fMRI work, these results establish fNIRS as an effective tool to investigate cortical contributions to anticipation of effortful behavior. This is especially useful if one requires testing large samples (e.g., to target individual differences), populations with contraindication for functional MRI (e.g., infants or patients with metal implants), or subjects in more naturalistic environments (e.g., work or sport). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Analogical reasoning and prefrontal cortex: evidence for separable retrieval and integration mechanisms.

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    Bunge, Silvia A; Wendelken, Carter; Badre, David; Wagner, Anthony D

    2005-03-01

    The present study examined the contributions of prefrontal cortex (PFC) subregions to two component processes underlying verbal analogical reasoning: semantic retrieval and integration. Event-related functional magnetic resonance imaging data were acquired while subjects performed propositional analogy and semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1), followed by an instructional cue and a second word pair (pair 2). On analogy trials, subjects evaluated whether pair 2 was semantically analogous to pair 1. On semantic trials, subjects indicated whether the pair 2 words were semantically related to each other. Thus, analogy--but not semantic--trials required integration across multiple retrieved relations. To identify regions involved in semantic retrieval, we manipulated the associative strength of pair 1 words in both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative strength, consistent with a role in controlled semantic retrieval. Left frontopolar cortex was insensitive to associative strength, but was more sensitive to integration demands than was aLIPC, consistent with a role in integrating the products of semantic retrieval to evaluate whether distinct representations are analogous. Right dorsolateral PFC exhibited a profile consistent with a role in response selection rather than retrieval or integration. These findings indicate that verbal analogical reasoning depends on multiple, PFC-mediated computations.

  7. Perceptual decision-making difficulty modulates feedforward effective connectivity to the dorsolateral prefrontal cortex

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    Bidhan eLamichhane

    2015-09-01

    Full Text Available Diverse cortical structures are known to coordinate activity as a network in relaying and processing of visual information to discriminate visual objects. However, how this discrimination is achieved is still largely unknown. To contribute to answering this question, we used face-house categorization tasks with three levels of noise in face and house images in functional magnetic resonance imaging (fMRI experiments involving thirty-three participants. The behavioral performance error and response time (RT were correlated with noise in face-house images. We then built dynamical causal models (DCM of fMRI blood-oxygenation level dependent (BOLD signals from the face and house category-specific regions in ventral temporal cortex, the fusiform face area (FFA and parahippocampal place area (PPA, and the dorsolateral prefrontal cortex (dlPFC. We found a strong feed-forward intrinsic connectivity pattern from FFA and PPA to dlPFC. Importantly, the feed-forward connectivity to dlPFC was significantly modulated by the perception of both faces and houses. The dlPFC-BOLD activity, the connectivity from FFA and PPA to the dlPFC all increased with noise level. These results suggest that the FFA-PPA-dlPFC network plays an important role for relaying and integrating competing sensory information to arrive at perceptual decisions.

  8. Maintenance of non-consciously presented information engages the prefrontal cortex

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    Fredrik eBergström

    2014-11-01

    Full Text Available Conscious processing is generally seen as required for flexible and willful actions, as well as for tasks that require durable information maintenance. Here we present research that questions the assumption that only consciously perceived information is durable (> 500 ms. Using the attentional blink phenomenon, we rendered otherwise relatively clearly perceived letters non-conscious. In a first experiment we systematically manipulated the delay between stimulus presentation and response, for the purpose of estimating the durability of non-conscious perceptual representations. For items reported not seen, we found that behavioral performance was better than chance across intervals up to 15 seconds. In a second experiment we used fMRI to investigate the neural correlates underlying the maintenance of non-conscious perceptual representations. Critically, the relatively long delay period demonstrated in experiment 1 enabled isolation of the signal change specifically related to the maintenance period, separate from stimulus presentation and response. We found sustained BOLD signal change in the right mid-lateral prefrontal cortex, orbitofrontal cortex, and crus II of the cerebellum during maintenance of non-consciously perceived information. These findings are consistent with the controversial claim that working-memory mechanisms are involved in the short-term maintenance of non-conscious perceptual representations.

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

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    Tachibana Atsumichi

    2012-05-01

    Full Text Available Abstract 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 degr