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Sample records for vglut1 prefrontal increase

  1. Cerebral level of vGlut1 is increased and level of glycine is decreased in TgSwDI mice

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    Timmer, N.M.; Metaxas, A.; Stelt, I. van der; Kluijtmans, L.A.; Berckel, B.N. van; Verbeek, M.M.

    2014-01-01

    Amyloid-beta (Abeta) deposition, one of the main hallmarks of Alzheimer's disease (AD), has been linked to glutamatergic dysfunction, i.e., increased stimulation of synaptic glutamate receptors that may ultimately result in neuronal loss. It was our aim to study the effect of Abeta on multiple

  2. Expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in the rat dental pulp and trigeminal ganglion following inflammation.

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    Eun Sun Yang

    Full Text Available There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG following complete Freund's adjuvant (CFA application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis.The density of VGLUT2- immunopositive (+ axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group.These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation.

  3. Bacopa monnieri (Brahmi) Enhanced Cognitive Function and Prevented Cognitive Impairment by Increasing VGLUT2 Immunodensity in Prefrontal Cortex of Sub-Chronic Phencyclidine Rat Model of Schizophrenia.

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    Piyabhan, Pritsana; Wetchateng, Thanitsara

    2015-04-01

    Glutamatergic hypofunction is affected in schizophrenia. The decrement ofpresynaptic glutamatergic marker remarkably vesicular glutamate transporter type 1 (VGLUT1) indicates the deficit ofglutamatergic and cognitive function in schizophrenic brain. However there have been afew studies in VGLUT2. Brahmi, a traditional herbal medicine, might be a new frontier of cognitive deficit treatment and prevention in schizophrenia by changing cerebral VGLUT2 density. To study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition task and cerebral VGLUT2 immunodensity in sub-chronic phencyclidine (PCP) rat model of schizophrenia. Cognitive enhancement effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP + Brahmi. Neuroprotective effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: Brahmi + PCP Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition task. VGLUT2 immunodensity was measured in prefrontal cortex, striatum, cornu ammonis fields 1 (CA1) and 2/3 (CA2/3) of hippocampus using immunohistochemistry. DR was significantly reduced in PCP group compared with control. This occurred alongside VGLUT2 reduction in prefrontal cortex, but not in striatum, CA1 or CA2/3. Both PCP + Brahmi and Brahmi + PCP groups showed an increased DR score up to normal, which occurred alongside a significantly increased VGLUT2 immunodensity in the prefrontal cortex, compared with PCP group. The decrement of VGLUT2 density in prefrontal cortex resulted in cognitive deficit in rats receiving PCP. Interestingly, receiving Brahmi after PCP administration can restore this cognitive deficit by increasing VGLUT2 density in prefrontal cortex. This investigation is defined as Brahmi's cognitive enhancement effect. Additionally, receiving Brahmi before PCP administration can also prevent cognitive impairment by

  4. Gestational and early postnatal hypothyroidism alters VGluT1 and VGAT bouton distribution in the neocortex and hippocampus, and behavior in rats

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    Daniela eNavarro

    2015-02-01

    Full Text Available Thyroid hormones are fundamental for the expression of genes involved in the development of the CNS and their deficiency is associated with a wide spectrum of neurological diseases including mental retardation, attention deficit-hyperactivity disorder and autism spectrum disorders. We examined in rat whether developmental and early postnatal hypothyroidism affects the distribution of vesicular glutamate transporter-1 (VGluT1; glutamatergic and vesicular inhibitory amino acid transporter (VGAT; GABAergic immunoreactive (ir boutons in the hippocampus and somatosensory cortex, and the behavior of the pups. Hypothyroidism was induced by adding 0.02% methimazole (MMI and 1% KClO4 to the drinking water starting at embryonic day 10 (E10; developmental hypothyroidism and E21 (early postnatal hypothyroidism until day of sacrifice at postnatal day 50. Behavior was studied using the acoustic prepulse inhibition (somatosensory attention and the elevated plus-maze (anxiety-like assessment tests. The distribution, density and size of VGlut1-ir and VGAT-ir boutons in the hippocampus and somatosensory cortex was abnormal in MMI pups and these changes correlate with behavioral changes, as prepulse inhibition of the startle response amplitude was reduced, and the percentage of time spent in open arms increased. In conclusion, both developmental and early postnatal hypothyroidism significantly decreases the ratio of GABAergic to glutamatergic boutons in dentate gyrus leading to an abnormal flow of information to the hippocampus and infragranular layers of the somatosensory cortex, and alter behavior in rats. Our data show cytoarchitectonic alterations in the basic excitatory hippocampal loop, and in local inhibitory circuits of the somatosensory cortex and hippocampus that might contribute to the delayed neurocognitive outcome observed in thyroid hormone deficient children born in iodine deficient areas, or suffering from congenital hypothyroidism.

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

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

    2017-07-01

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

  6. Damage to the prefrontal cortex increases utilitarian moral judgements

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    Koenigs, Michael; Young, Liane; Adolphs, Ralph; Tranel, Daniel; Cushman, Fiery; Hauser, Marc; Damasio, Antonio

    2007-01-01

    The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social em...

  7. Coexpression of glutamate vesicular transporter (VGLUT1) and choline acetyltransferase (ChAT) proteins in fetal rat hippocampal neurons in culture.

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    Bhargava, Neelima; Das, Mainak; Edwards, Darin; Stancescu, Maria; Kang, Jung-Fong; Hickman, James J

    2010-09-01

    A very small population of choline acetyltransferase (ChAT) immunoreactive cells is observed in all layers of the adult hippocampus. This is the intrinsic source of the hippocampal cholinergic innervation, in addition to the well-established septo-hippocampal cholinergic projection. This study aimed at quantifying and identifying the origin of this small population of ChAT-immunoreactive cells in the hippocampus at early developmental stages, by culturing the fetal hippocampal neurons in serum-free culture and on a patternable, synthetic silane substrate N-1 [3-(trimethoxysilyl) propyl] diethylenetriamine. Using this method, a large proportion of glutamatergic (glutamate vesicular transporter, VGLUT1-immunoreactive) neurons, a small fraction of GABAergic (GABA-immunoreactive) neurons, and a large proportion of cholinergic (ChAT-immunoreactive) neurons were observed in the culture. Interestingly, most of the glutamatergic neurons that expressed glutamate vesicular transporter (VGLUT1) also co-expressed ChAT proteins. On the contrary, when the cultures were double-stained with GABA and ChAT, colocalization was not observed. Neonatal and adult rat hippocampal neurons were also cultured to verify whether these more mature neurons also co-express VGLUT1 and ChAT proteins in culture. Colocalization of VGLUT1 and ChAT in these relatively more mature neurons was not observed. One possible explanation for this observation is that the neurons have the ability to synthesize multiple neurotransmitters at a very early stage of development and then with time follows a complex, combinatorial strategy of electrochemical coding to determine their final fate.

  8. Damage to the prefrontal cortex increases utilitarian moral judgements.

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    Koenigs, Michael; Young, Liane; Adolphs, Ralph; Tranel, Daniel; Cushman, Fiery; Hauser, Marc; Damasio, Antonio

    2007-04-19

    The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions, produce an abnormally 'utilitarian' pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person's life to save a number of other lives). In contrast, the VMPC patients' judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements.

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

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

    2016-07-01

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

  10. Increased Firing Irregularity as an Emergent Property of Neural-State Transition in Monkey Prefrontal Cortex

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    Sakamoto, Kazuhiro; Katori, Yuichi; Saito, Naohiro; Yoshida, Shun; Aihara, Kazuyuki; Mushiake, Hajime

    2013-01-01

    Flexible behaviors are organized by complex neural networks in the prefrontal cortex. Recent studies have suggested that such networks exhibit multiple dynamical states, and can switch rapidly from one state to another. In many complex systems such as the brain, the early-warning signals that may predict whether a critical threshold for state transitions is approaching are extremely difficult to detect. We hypothesized that increases in firing irregularity are a crucial measure for predicting state transitions in the underlying neuronal circuits of the prefrontal cortex. We used both experimental and theoretical approaches to test this hypothesis. Experimentally, we analyzed activities of neurons in the prefrontal cortex while monkeys performed a maze task that required them to perform actions to reach a goal. We observed increased firing irregularity before the activity changed to encode goal-to-action information. Theoretically, we constructed theoretical generic neural networks and demonstrated that changes in neuronal gain on functional connectivity resulted in a loss of stability and an altered state of the networks, accompanied by increased firing irregularity. These results suggest that assessing the temporal pattern of neuronal fluctuations provides important clues regarding the state stability of the prefrontal network. We also introduce a novel scheme that the prefrontal cortex functions in a metastable state near the critical point of bifurcation. According to this scheme, firing irregularity in the prefrontal cortex indicates that the system is about to change its state and the flow of information in a flexible manner, which is essential for executive functions. This metastable and/or critical dynamical state of the prefrontal cortex may account for distractibility and loss of flexibility in the prefrontal cortex in major mental illnesses such as schizophrenia. PMID:24349020

  11. Training improves multitasking performance by increasing the speed of information processing in human prefrontal cortex.

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    Dux, Paul E; Tombu, Michael N; Harrison, Stephenie; Rogers, Baxter P; Tong, Frank; Marois, René

    2009-07-16

    Our ability to multitask is severely limited: task performance deteriorates when we attempt to undertake two or more tasks simultaneously. Remarkably, extensive training can greatly reduce such multitasking costs. While it is not known how training alters the brain to solve the multitasking problem, it likely involves the prefrontal cortex given this brain region's purported role in limiting multitasking performance. Here, we show that the reduction of multitasking interference with training is not achieved by diverting the flow of information processing away from the prefrontal cortex or by segregating prefrontal cells into independent task-specific neuronal ensembles, but rather by increasing the speed of information processing in this brain region, thereby allowing multiple tasks to be processed in rapid succession. These results not only reveal how training leads to efficient multitasking, they also provide a mechanistic account of multitasking limitations, namely the poor speed of information processing in human prefrontal cortex.

  12. Increased perceived stress is related to decreased prefrontal cortex volumes among older adults.

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    Moreno, Georgina L; Bruss, Joel; Denburg, Natalie L

    2017-05-01

    Several of the brain regions vulnerable to increased levels of stress (i.e., hippocampus and prefrontal cortex) are also known to undergo disproportionate decline during normal aging. To date, surprisingly little research has examined the effects of stress on the brain among healthy human populations, much less in the elderly. The aim of the current study was to investigate the relationship between chronic stress and brain morphometry in regions known for their involvement in the stress response, namely the prefrontal cortex, hippocampus, and amygdala, in a sample of healthy older adults. The Perceived Stress Scale and structural magnetic resonance imaging (MRI) were collected in 28 older adult individuals aged 65 to 90 years. Gray and white matter volumes in various regions of interest in the prefrontal cortex and medial temporal lobes were calculated using semiautomated segmentation tools. Perceived stress was negatively correlated with overall prefrontal cortex (PFC) volume, specifically in overall white matter volume of the PFC. Additionally, perceived stress was negatively correlated with gray and white matter volumes in lateral regions of the PFC, specifically, in the ventrolateral and dorsolateral PFC. Perceived stress was not significantly related to medial temporal lobe volumes. These findings suggest that among healthy older adults, there is a salient relationship between prefrontal cortex volumes and levels of perceived stress. This research fills a critical gap in the current literature and provides initial groundwork for future studies investigating the relationship between perceived stress and the prefrontal cortex in the context of healthy aging.

  13. Transcranial direct current stimulation over the left prefrontal cortex increases randomness of choice in instrumental learning.

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    Turi, Zsolt; Mittner, Matthias; Opitz, Alexander; Popkes, Miriam; Paulus, Walter; Antal, Andrea

    2015-02-01

    There is growing evidence from neuro-computational studies that instrumental learning involves the dynamic interaction of a computationally rigid, low-level striatal and a more flexible, high-level prefrontal component. To evaluate the role of the prefrontal cortex in instrumental learning, we applied anodal transcranial direct current stimulation (tDCS) optimized for the left dorsolateral prefrontal cortex, by using realistic MR-derived finite element model-based electric field simulations. In a study with a double-blind, sham-controlled, repeated-measures design, sixteen male participants performed a probabilistic learning task while receiving anodal and sham tDCS in a counterbalanced order. Compared to sham tDCS, anodal tDCS significantly increased the amount of maladaptive shifting behavior after optimal outcomes during learning when reward probabilities were highly dissociable. Derived parameters of the Q-learning computational model further revealed a significantly increased model parameter that was sensitive to random action selection in the anodal compared to the sham tDCS session, whereas the learning rate parameter was not influenced significantly by tDCS. These results congruently indicate that prefrontal tDCS during instrumental learning increased randomness of choice, possibly reflecting the influence of the cognitive prefrontal component. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 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.

  15. α-Synuclein expression in the mouse cerebellum is restricted to VGluT1 excitatory terminals and is enriched in unipolar brush cells.

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    Lee, Sun Kyong; Sillitoe, Roy V; Silva, Coralie; Martina, Marco; Sekerkova, Gabriella

    2015-10-01

    α-Synuclein has a crucial role in synaptic vesicle release and synaptic membrane recycling. Although its general expression pattern has been described in the cerebellum, the precise cerebellar structures where α-synuclein is localized are poorly understood. To address this question, we used α-synuclein immunohistochemistry in adult mice cerebellar sections. We found that α-synuclein labels glutamatergic but not glycinergic and GABAergic synaptic terminals in the molecular and granule cell layers. α-Synuclein was preferentially expressed in parallel and mossy fiber synaptic terminals that also express vesicular glutamate transporter 1 (VGluT1), while it was not detected in VGluT2-positive climbing fibers. α-Synuclein was particularly enriched in lobules IX and X, a region known to contain a high density of unipolar brush cells (UBCs). To elucidate whether the α-synuclein-positive mossy fibers belong to UBCs, we double-labeled cerebellar sections with antibodies to α-synuclein and UBC-type-specific markers (calretinin for type I and metabotropic glutamate receptor 1α (mGluR1α) for type II UBCs) and took advantage of organotypic cerebellar cultures (in which all mossy fibers are UBC axons) and moonwalker mice (in which almost all UBCs are ablated) and found that both type I and type II UBCs express α-synuclein. In moonwalker mutant cerebella, the α-synuclein/VGluT1 immunolabeling showed a dramatic decrease in the vestibulocerebellum that correlated with the absence of UBC. α-Synuclein appears to be an excellent marker for intrinsic mossy fibers of the VGluT1 subset in conjunction with UBCs of both subtypes.

  16. Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System xc− Activity in the Medial Prefrontal Cortex

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    Lutgen, Victoria; Qualmann, Krista; Resch, Jon; Kong, Linghai; Choi, SuJean; Baker, David A.

    2012-01-01

    Rationale Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc−, a cystine- glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives Our goal was to determine whether increased system xc− activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods In situ hybridization was used to map mRNA expression of xCT, the active subunit of system xc−, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-acetylcysteine (10–100 μM) and the system xc− inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc− activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc− activity. Results The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intra-prefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-acetylcysteine was without effect when co-infused with CPG (0.5 μM), indicating an involvement of system xc−. Conclusions These results indicate that phencyclidine disrupts sensorimotor gating through system xc− independent mechanisms, but that increasing cystine-glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine. PMID:23192314

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

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    Erik eAsp

    2012-07-01

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

  18. Reduction in phencyclidine induced sensorimotor gating deficits in the rat following increased system xc⁻ activity in the medial prefrontal cortex.

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    Lutgen, Victoria; Qualmann, Krista; Resch, Jon; Kong, Linghai; Choi, Sujean; Baker, David A

    2013-04-01

    Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc(-), a cystine-glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Our goal was to determine whether increased system xc(-) activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc(-), in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3-3 mg/kg, sc). N-Acetylcysteine (10-100 μM) and the system xc(-) inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc(-) activity, respectively. The uptake of (14)C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc(-) activity. The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of (14)C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10-100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc(-). These results indicate that phencyclidine disrupts sensorimotor gating through system xc(-) independent mechanisms, but that increasing cystine-glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine.

  19. Increased low- and high-frequency oscillatory activity in the prefrontal cortex of fibromyalgia patients

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    Manyoel eLim

    2016-03-01

    Full Text Available Recent human neuroimaging studies have suggested that fibromyalgia (FM, a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC and orbitofrontal cortex (OFC. Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM.

  20. Increased stress vulnerability after a prefrontal cortex lesion in female rats

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    Gerrits, M; Westenbroek, C; Fokkema, DS; Jongsma, ME; Den Boer, JA; Ter Horst, GJ

    2003-01-01

    Neuroimaging studies in patients suffering from affective disorders have shown decreased volume and reduced regional cerebral blood flow in multiple areas of the prefrontal cortex, including the medial prefrontal cortex and the orbitofrontal cortex. This aberrant brain activity is among other things

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

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

    2017-09-20

    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.

  2. 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.

  3. Media multitasking is associated with distractibility and increased prefrontal activity in adolescents and young adults.

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    Moisala, M; Salmela, V; Hietajärvi, L; Salo, E; Carlson, S; Salonen, O; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

    2016-07-01

    The current generation of young people indulges in more media multitasking behavior (e.g., instant messaging while watching videos) in their everyday lives than older generations. Concerns have been raised about how this might affect their attentional functioning, as previous studies have indicated that extensive media multitasking in everyday life may be associated with decreased attentional control. In the current study, 149 adolescents and young adults (aged 13-24years) performed speech-listening and reading tasks that required maintaining attention in the presence of distractor stimuli in the other modality or dividing attention between two concurrent tasks. Brain activity during task performance was measured using functional magnetic resonance imaging (fMRI). We studied the relationship between self-reported daily media multitasking (MMT), task performance and brain activity during task performance. The results showed that in the presence of distractor stimuli, a higher MMT score was associated with worse performance and increased brain activity in right prefrontal regions. The level of performance during divided attention did not depend on MMT. This suggests that daily media multitasking is associated with behavioral distractibility and increased recruitment of brain areas involved in attentional and inhibitory control, and that media multitasking in everyday life does not translate to performance benefits in multitasking in laboratory settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Motivational incentives lead to a strong increase in lateral prefrontal activity after self-control exertion.

    Science.gov (United States)

    Luethi, Matthias S; Friese, Malte; Binder, Julia; Boesiger, Peter; Luechinger, Roger; Rasch, Björn

    2016-10-01

    Self-control is key to success in life. Initial acts of self-control temporarily impair subsequent self-control performance. Why such self-control failures occur is unclear, with prominent models postulating a loss of a limited resource vs a loss of motivation, respectively. Here, we used functional magnetic resonance imaging to identify the neural correlates of motivation-induced benefits on self-control. Participants initially exerted or did not exert self-control. In a subsequent Stroop task, participants performed worse after exerting self-control, but not if they were motivated to perform well by monetary incentives. On the neural level, having exerted self-control resulted in decreased activation in the left inferior frontal gyrus. Increasing motivation resulted in a particularly strong activation of this area specifically after exerting self-control. Thus, after self-control exertion participants showed more prefrontal neural activity without improving performance beyond baseline level. These findings suggest that impaired performance after self-control exertion may not exclusively be due to a loss of motivation. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  5. 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.

  6. Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Bin Xu

    2005-10-01

    Full Text Available We have previously reported linkage of markers on chromosome 1q22 to schizophrenia, a finding supported by several independent studies. Within this linkage region, we have identified significant linkage disequilibrium between schizophrenia and markers within the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON. Prior sequencing of the ten exons of CAPON failed to reveal a coding mutation associated with illness.We screened a human fetal brain cDNA library and identified a new isoform of CAPON that consists of the terminal two exons of the gene, and verified the expression of the predicted corresponding protein in human dorsolateral prefrontal cortex (DLPFC. We examined the expression levels of both the ten-exon CAPON transcript and this new isoform in postmortem brain samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA from the DLPFC in 105 individuals (35 with schizophrenia, 35 with bipolar disorder, and 35 psychiatrically normal controls revealed significantly (p < 0.005 increased expression of the new isoform in both schizophrenia and bipolar disorder. Furthermore, this increased expression was significantly associated (p < 0.05 with genotype at three single-nucleotide polymorphisms previously identified as being in linkage disequilibrium with schizophrenia.Based on the known interactions between CAPON, neuronal nitric oxide synthase (nNOS, and proteins associated with the N-methyl-D-aspartate receptor (NMDAR complex, overexpression of either CAPON isoform would be expected to disrupt the association between nNOS and the NMDAR, leading to changes consistent with the NMDAR hypofunctioning hypothesis of schizophrenia. This study adds support to a role of CAPON in schizophrenia, produces new evidence implicating this gene in the etiology of bipolar disorder, and suggests a possible mechanism of action of CAPON in psychiatric illness.

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

    Science.gov (United States)

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

    2012-01-01

    We have proposed the False Tagging Theory (FTT) 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 FTT to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex (vmPFC) 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 vmPFC, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with vmPFC 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 vmPFC 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.

  8. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    Science.gov (United States)

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  9. 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.

  10. 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.

  11. Sex Differences in Autism-Like Behavioral Phenotypes and Postsynaptic Receptors Expression in the Prefrontal Cortex of TERT Transgenic Mice.

    Science.gov (United States)

    Kim, Ki Chan; Cho, Kyu Suk; Yang, Sung Min; Gonzales, Edson Luck; Valencia, Schley; Eun, Pyeong Hwa; Choi, Chang Soon; Mabunga, Darine Froy; Kim, Ji-Woon; Noh, Judy Kyoungju; Kim, Hee Jin; Jeon, Se Jin; Han, Seol-Heui; Bahn, Geon Ho; Shin, Chan Young

    2017-07-01

    Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Increased hippocampal, thalamic, and prefrontal hemodynamic response to an urban noise stimulus in schizophrenia.

    Science.gov (United States)

    Tregellas, Jason R; Ellis, Jamey; Shatti, Shireen; Du, Yiping P; Rojas, Donald C

    2009-03-01

    People with schizophrenia often have difficulty ignoring unimportant noises in the environment. While experimental measures of sensory gating have yielded insight into neurobiological mechanisms related to this deficit, the degree to which these measures reflect the real-world experience of people with schizophrenia is unknown. The goal of this study was to develop a clinically relevant sensory gating paradigm and to assess differences in brain hemodynamic responses during the task in schizophrenia. Thirty-five participants, including 18 outpatients with schizophrenia and 17 healthy comparison subjects, underwent scanning on a 3-T MR system while passively listening to an "urban white noise" stimulus, a mixture of common sounds simulating a busy urban setting, including multiple conversations and events recorded from a neighborhood gathering, music, and talk radio. P50 evoked responses from a typical paired-click sensory gating task also were measured. Listening to the urban white noise stimulus produced robust activation of the auditory pathway in all participants. Activation was observed in the bilateral primary and secondary auditory cortices, medial geniculate nuclei, and inferior colliculus. Greater activation was observed in the schizophrenia patients relative to the comparison subjects in the hippocampus, thalamus, and prefrontal cortex. Higher P50 test/conditioning ratios also were observed in the schizophrenia patients. These evoked responses correlated with hemodynamic responses in the hippocampus and the prefrontal cortex. The finding of greater activation of the hippocampus, thalamus, and prefrontal cortex during a sensory gating task with high face validity further supports the involvement of these brain regions in gating deficits in schizophrenia. This link is strengthened by the observed correlation between evoked responses in the paired-click paradigm and hemodynamic responses in a functional MRI sensory gating paradigm.

  14. Mechanical stimulation evokes rapid increases in extracellular adenosine concentration in the prefrontal cortex

    Science.gov (United States)

    Ross, Ashley E.; Nguyen, Michael D.; Privman, Eve; Venton, B. Jill

    2014-01-01

    Mechanical perturbations can release ATP, which is broken down to adenosine. In this work, we used carbon-fiber microelectrodes and fast-scan cyclic voltammetry to measure mechanically-stimulated adenosine in the brain by lowering the electrode 50 μm. Mechanical stimulation evoked adenosine in vivo (average: 3.3 ± 0.6 μM) and in brain slices (average: 0.8 ± 0.1 μM) in the prefrontal cortex. The release was transient, lasting 18 ± 2 s. Lowering a 15 μm diameter glass pipette near the carbon-fiber microelectrode produced similar results as lowering the actual microelectrode. However, applying a small puff of artificial cerebral spinal fluid was not sufficient to evoke adenosine. Multiple stimulations within a 50 μm region of a slice did not significantly change over time or damage cells. Chelating calcium with EDTA or blocking sodium channels with tetrodotoxin (TTX) significantly decreased mechanically evoked adenosine, signifying that the release is activity-dependent. An alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), did not affect mechanically-stimulated adenosine; however, the nucleoside triphosphate diphosphohydrolase 1,2 and 3 (NTDPase) inhibitor POM-1 significantly reduced adenosine so a portion of adenosine is dependent on extracellular ATP metabolism. Thus, mechanical perturbations from inserting a probe in the brain cause rapid, transient adenosine signaling which might be neuroprotective. PMID:24606335

  15. Abnormally increased effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during emotion labeling in bipolar disorder

    Science.gov (United States)

    Almeida, Jorge R. C.; Mechelli, Andrea; Hassel, Stefanie; Versace, Amelia; Kupfer, David J.; Phillips, Mary L.

    2009-01-01

    Emotional liability and mood dysregulation characterize bipolar disorder (BD), yet no study has examined effective connectivity between parahippocampal gyrus and prefrontal cortical regions in ventromedial and dorsal/lateral neural systems subserving mood regulation in BD. Forty-six individuals (age range: 18–56 years); 21 with a DSM-IV diagnosis of BD, type I currently remitted; 25 age- and gender-matched healthy controls (HC). Participants performed an event-related paradigm, viewing mild and intense happy and neutral faces. We employed dynamic causal modeling (DCM) to identify significant alterations in effective connectivity between BD and HC. Bayes model selection was used to determine the best model. The right parahippocampal gyrus (PHG) and right subgenual cingulate gyrus (sgCG) were included as representative regions of the ventromedial neural system. The right dorsolateral prefrontal cortex (DLPFC) region was included as representative of the dorsal/lateral neural system. Right PHG-sgCG effective connectivity was significantly greater in BD than HC, reflecting more rapid, forward PHG-sgCG signaling in BD than HC. There was no between-group difference in sgCG-DLPFC effective connectivity. In BD, abnormally increased right PHG-sgCG effective connectivity and reduced right PHG activity to emotional stimuli suggest a dysfunctional ventromedial neural system implicated in early stimulus appraisal, encoding and automatic regulation of emotion, that may represent a pathophysiological functional neural mechanism for mood dysregulation in BD. PMID:19910166

  16. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression

    DEFF Research Database (Denmark)

    Márquez, C; Poirier, G L; Cordero, M I

    2013-01-01

    Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress...... with face, construct and predictive validity. We show that male rats submitted to fear-induction experiences during the peripubertal period exhibit high and sustained rates of increased aggression at adulthood, even against unthreatening individuals, and increased testosterone/corticosterone ratio...... in the serotonergic system in the prefrontal cortex-and pointing at epigenetic control of the MAOA gene-in the establishment of the link between peripubertal stress and later pathological aggression. Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence...

  17. Prefrontal cortical parvalbumin and somatostatin expression and cell density increase during adolescence and are modified by BDNF and sex.

    Science.gov (United States)

    Du, X; Serena, K; Hwang, W; Grech, A M; Wu, Y W C; Schroeder, A; Hill, R A

    2018-02-03

    Brain-derived neurotrophic factor (BDNF) is known to play a critical role early in the development of cortical GABAergic interneurons. Recently our laboratory and others have shown protracted development of specific subpopulations of GABAergic interneurons extending into adolescence. BDNF expression also changes significantly across adolescent development. However the role of BDNF in regulating GABAergic changes across adolescence remains unclear. Here, we performed a week-by-week analysis of the protein expression and cell density of three major GABAergic interneurons, parvalbumin (PV), somatostatin (SST) and calretinin (Cal) in the medial prefrontal cortex from prepubescence (week 3) to adulthood (week 12). In order to assess how BDNF and sex might influence the adolescent trajectory of GABAergic interneurons we compared WT as well as BDNF heterozygous (+/-) male and female mice. In both males and females PV expression increases during adolescent development in the mPFC. Compared to wild-types, PV expression was reduced in male but not female BDNF+/- mice throughout adolescent development. This reduction in protein expression corresponded with reduced cell density, specifically within the infralimbic prefrontal cortex. SST expression increased in early adolescent WT females and this upregulation was delayed in BDNF+/-. SST cell density also increased in early adolescent mPFC of WT female mice, with BDNF+/- again showing a reduced pattern of expression. Cal protein expression was also sex-dependently altered across adolescence with WT males showing a steady decline but that of BDNF+/- remaining unaltered. Reduced cell density in on the other hand was observed particularly in male BDNF+/- mice. In females, Cal protein expression and cell density remained largely stable. Our results show that PV, SST and calretinin interneurons are indeed still developing into early adolescence in the mPFC and that BDNF plays a critical, sex-specific role in mediating expression and

  18. Sustained anxiety increases amygdala–dorsomedial prefrontal coupling: a mechanism for maintaining an anxious state in healthy adults

    Science.gov (United States)

    Vytal, Katherine E.; Overstreet, Cassie; Charney, Danielle R.; Robinson, Oliver J.; Grillon, Christian

    2014-01-01

    Background Neuroimaging research has traditionally explored fear and anxiety in response to discrete threat cues (e.g., during fear conditioning). However, anxiety is a sustained aversive state that can persist in the absence of discrete threats. Little is known about mechanisms that maintain anxiety states over a prolonged period. Here, we used a robust translational paradigm (threat of shock) to induce sustained anxiety. Recent translational work has implicated an amygdala–prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To explore the functional homologues of this circuitry in humans, we used a novel paradigm to examine the impact of sustained anticipatory anxiety on amygdala–PFC intrinsic connectivity. Methods Task-independent fMRI data were collected in healthy participants during long-duration periods of shock anticipation and safety. We examined intrinsic functional connectivity. Results Our study involved 20 healthy participants. During sustained anxiety, amygdala activity was positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was associated with increased amygdala–DMPFC coupling. In addition, induced anxiety was associated with positive coupling between regions involved in defensive responding, and decreased coupling between regions involved in emotional control and the default mode network. Limitations Inferences regarding anxious pathology should be made with caution because this study was conducted in healthy participants. Conclusion Findings suggest that anticipatory anxiety increases intrinsic amygdala–DMPFC coupling and that the DMPFC may serve as a functional homologue for the rodent prefrontal regions by sustaining anxiety. Future research may use this defensive neural context to identify bio-markers of risk for anxious pathology and target these circuits for therapeutic intervention. PMID:24886788

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

    Directory of Open Access Journals (Sweden)

    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

  20. Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months.

    Science.gov (United States)

    Heller, Aaron S; Johnstone, Tom; Peterson, Michael J; Kolden, Gregory G; Kalin, Ned H; Davidson, Richard J

    2013-11-01

    Emotion regulation is critically disrupted in depression, and the use of paradigms that tap into these processes may uncover essential changes in neurobiology during treatment. In addition, because neuroimaging outcome studies of depression commonly use only baseline and end-point data-which are more prone to week-to-week noise in symptomatology-we sought to use all data points over the course of a 6-month trial. To examine changes in neurobiology resulting from successful treatment. Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from 1 of 2 antidepressant treatments during a 6-month trial. Twenty-one patients with major depressive disorder and without other Axis I or Axis II diagnoses were scanned before treatment and 2 and 6 months into treatment at the university's functional magnetic resonance imaging facility. Venlafaxine hydrochloride extended release (with doses of up to 300 mg) or fluoxetine hydrochloride (with doses of up to 80 mg). Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm, as well as regular assessments of symptom severity using the Hamilton Depression Rating Scale. For use of all data points, slope trajectories were calculated for rate of change in depression severity and for rate of change in neural engagement. The depressed individuals who showed the steepest decrease in depression severity over the 6-month period were the same individuals who showed the most rapid increases in activity in Brodmann area 10 and the right dorsolateral prefrontal cortex activity when regulating negative affect over the same time frame. This relationship was more robust when using only the baseline and end-point data. Changes in prefrontal cortex engagement when regulating negative affect correlate with changes in depression severity over 6 months. These results are buttressed by calculating these statistics, which are more reliable and

  1. Exposure to Blue Light Increases Subsequent Functional Activation of the Prefrontal Cortex During Performance of a Working Memory Task.

    Science.gov (United States)

    Alkozei, Anna; Smith, Ryan; Pisner, Derek A; Vanuk, John R; Berryhill, Sarah M; Fridman, Andrew; Shane, Bradley R; Knight, Sara A; Killgore, William D S

    2016-09-01

    Prolonged exposure to blue wavelength light has been shown to have an alerting effect, and enhances performance on cognitive tasks. A small number of studies have also shown that relatively short exposure to blue light leads to changes in functional brain responses during the period of exposure. The extent to which blue light continues to affect brain functioning during a cognitively challenging task after cessation of longer periods of exposure (i.e., roughly 30 minutes or longer), however, has not been fully investigated. A total of 35 healthy participants (18 female) were exposed to either blue (469 nm) (n = 17) or amber (578 nm) (n = 18) wavelength light for 30 minutes in a darkened room, followed immediately by functional magnetic resonance imaging (fMRI) while undergoing a working memory task (N-back task). Participants in the blue light condition were faster in their responses on the N-back task and showed increased activation in the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex compared to those in the amber control light condition. Furthermore, greater activation within the VLPFC was correlated with faster N-back response times. This is the first study to suggest that a relatively brief, single exposure to blue light has a subsequent beneficial effect on working memory performance, even after cessation of exposure, and leads to temporarily persisting functional brain changes within prefrontal brain regions associated with executive functions. These findings may have broader implication for using blue-enriched light in a variety of work settings where alertness and quick decision-making are important. © 2016 Associated Professional Sleep Societies, LLC.

  2. Bacopa monnieri (Brahmi) improved novel object recognition task and increased cerebral vesicular glutamate transporter type 3 in sub-chronic phencyclidine rat model of schizophrenia.

    Science.gov (United States)

    Piyabhan, Pritsana; Wannasiri, Supaporn; Naowaboot, Jarinyaporn

    2016-12-01

    Reduced vesicular glutamate transporter 1 (VGLUT1) and 2 (VGLUT2) indicate glutamatergic hypofunction leading to cognitive impairment in schizophrenia. However, VGLUT3 involvement in cognitive dysfunction has not been reported in schizophrenia. Brahmi (Bacopa monnieri) might be a new treatment and prevention for cognitive deficits in schizophrenia by acting on cerebral VGLUT3 density. We aimed to study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition and cerebral VGLUT3 immunodensity in sub-chronic (2 mg/kg, Bid, ip) phencyclidine (PCP) rat model of schizophrenia. Rats were assigned to three groups for cognitive enhancement effect study: Group 1, Control; Group 2, PCP administration; Group 3, PCP+Brahmi. A neuroprotective-effect study was also carried out. Rats were again assigned to three groups: Group 1, Control; Group 2, PCP administration; Group 3, Brahmi+PCP. Discrimination ratio (DR) representing cognitive ability was obtained from a novel object recognition task. VGLUT3 immunodensity was measured in the prefrontal cortex, striatum and cornu ammonis fields 1-3 (CA1-3) using immunohistochemistry. We found reduced DR in the PCP group, which occurred alongside VGLUT3 reduction in all brain areas. PCP+Brahmi showed higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex and striatum. Brahmi+PCP group showed a higher DR score with increased VGLUT3 immunodensity in the prefrontal cortex, striatum and CA1-3. We concluded that reduced cerebral VGLUT3 was involved in cognitive deficit in PCP-administrated rats. Receiving Brahmi after PCP restored cognitive deficit by increasing VGLUT3 in the prefrontal cortex and striatum. Receiving Brahmi before PCP prevented cognitive impairment by elevating VGLUT3 in prefrontal cortex, striatum and CA1-3. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia. © 2016 John Wiley & Sons Australia, Ltd.

  3. Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.

    Science.gov (United States)

    Muschamp, John W; Regina, Meredith J; Hull, Elaine M; Winter, Jerrold C; Rabin, Richard A

    2004-10-08

    The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 microM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

  4. The alpha7 nicotinic receptor agonist SSR180711 increases activity regulated cytoskeleton protein (Arc) gene expression in the prefrontal cortex of the rat

    DEFF Research Database (Denmark)

    Kristensen, Søren; Thomsen, Morten Skøtt; Hansen, Henrik H

    2007-01-01

    /kg) to adolescent rats, produced a dose- and time-dependent increase in the expression of Arc mRNA in the prefrontal cortex and the ventral orbital cortex. By contrast, no change in mRNA levels was detected in the parietal cortex and the CA1 of the hippocampus. These data show that alpha7 nAChR activates a subset...... of neurons in the rat prefrontal cortex and this activation likely is important for the attentional effects of this new class of drugs....

  5. Chronic Treatment with a Clinically Relevant Dose of Methylphenidate Increases Glutamate Levels in Cerebrospinal Fluid and Impairs Glutamatergic Homeostasis in Prefrontal Cortex of Juvenile Rats.

    Science.gov (United States)

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Coelho, Daniella M; Mussulini, Ben Hur; Pereira, Mery S L; Parisi, Mariana M; Barbé-Tuana, Florencia; de Oliveira, Diogo L; Vargas, Carmen R; Wyse, Angela T S

    2016-05-01

    The understanding of the consequences of chronic treatment with methylphenidate is very important since this psychostimulant is extensively prescribed to preschool age children, and little is known about the mechanisms underlying the persistent changes in behavior and neuronal function related with the use of methylphenidate. In this study, we initially investigate the effect of early chronic treatment with methylphenidate on amino acids profile in cerebrospinal fluid and prefrontal cortex of juvenile rats, as well as on glutamatergic homeostasis, Na(+),K(+)-ATPase function, and balance redox in prefrontal cortex of rats. Wistar rats at early age received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9% saline solution (controls), once a day, from the 15th to the 45th day of age. Twenty-four hours after the last injection, the animals were decapitated and the cerebrospinal fluid and prefrontal cortex were obtained. Results showed that methylphenidate altered amino acid profile in cerebrospinal fluid, increasing the levels of glutamate. Glutamate uptake was decreased by methylphenidate administration, but GLAST and GLT-1 were not altered by this treatment. In addition, the astrocyte marker GFAP was not altered by MPH. The activity and immunocontent of catalytic subunits (α1, α2, and α3) of Na(+),K(+)-ATPase were decreased in prefrontal cortex of rats subjected to methylphenidate treatment, as well as changes in α1 and α2 gene expression of catalytic α subunits of Na(+),K(+)-ATPase were also observed. CAT activity was increased and SOD/CAT ratio and sulfhydryl content were decreased in rat prefrontal cortex. Taken together, our results suggest that chronic treatment with methylphenidate at early age induces excitotoxicity, at least in part, due to inhibition of glutamate uptake probably caused by disturbances in the Na(+),K(+)-ATPase function and/or in protein damage observed in the prefrontal cortex.

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

    Science.gov (United States)

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

    2017-07-01

    + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  7. Dietary-induced binge eating increases prefrontal cortex neural activation to restraint stress and increases binge food consumption following chronic guanfacine.

    Science.gov (United States)

    Bello, Nicholas T; Walters, Amy L; Verpeut, Jessica L; Caverly, Jonathan

    2014-10-01

    Binge eating is a prominent feature of bulimia nervosa and binge eating disorder. Stress or perceived stress is an often-cited reason for binge eating. One notion is that the neural pathways that overlap with stress reactivity and feeding behavior are altered by recurrent binge eating. Using young adult female rats in a dietary-induced binge eating model (30 min access to binge food with or without 24-h calorie restriction, twice a week, for 6 weeks) we measured the neural activation by c-Fos immunoreactivity to the binge food (vegetable shortening mixed with 10% sucrose) in bingeing and non-bingeing animals under acute stress (immobilization; 1 h) or no stress conditions. There was an increase in the number of immunopositive cells in the dorsal medial prefrontal cortex (mPFC) in stressed animals previously exposed to the binge eating feeding schedules. Because attention deficit hyperactive disorder (ADHD) medications target the mPFC and have some efficacy at reducing binge eating in clinical populations, we examined whether chronic (2 weeks; via IP osmotic mini-pumps) treatment with a selective alpha-2A adrenergic agonist (0.5 mg/kg/day), guanfacine, would reduce binge-like eating. In the binge group with only scheduled access to binge food (30 min; twice a week; 8 weeks), guanfacine increased total calories consumed during the 30-min access period from the 2-week pre-treatment baseline and increased binge food consumption compared with saline-treated animals. These experiments suggest that mPFC is differentially activated in response to an immobilization stress in animals under different dietary conditions and chronic guanfacine, at the dose tested, was ineffective at reducing binge-like eating. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Increase in serotonin 5-HT sub 1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takeshi; Nishino, Naoki; Nakai, Hisao; Tanaka, Chikako (Kobe Univ. School of Medicine (Japan))

    1991-01-01

    Binding studies with ({sup 3}H)8-hydroxy-2-(di-n-propylamino)tetralin (({sup 3}H)8-OH-DPAT), a specific serotonin{sub 1A} (5-HT{sub 1A}) receptor agonist, were done on the autopsied brains from control subjects and from patients with chronic schizophrenia. In the controls, representative Scatchard plots for the specific ({sup 3}H)8-OH-DPAT bindings in the prefrontal cortex and hippocampus revealed a single component of high affinity binding site. The ({sup 3}H)8-OH-DPAT bindings to the prefrontal cortex and hippocampus were potently inhibited by serotonin and 5-HT{sub 1A} agonists, while other neurotransmitters, 5-HT{sub 2} and 5-HT{sub 3} related compounds did not inhibit the binding. The bindings were decreased in the presence of 0.1mM GTP and 0.1mM GppNHp but not in the presence of 0.1mM GMP. In the prefrontal and temporal cortices of schizophrenics, there was a significant increase in the specific ({sup 3}H)8-OH-DPAT binding, by 40% and 60%, respectively, with no change in the hippocampus, amygdala, cingulum, motor cortex, parietal or occipital cortex, as compared to findings in the controls.

  9. Effects of the combination of metyrapone and oxazepam on cocaine-induced increases in corticosterone in the medial prefrontal cortex and nucleus accumbens.

    Science.gov (United States)

    Keller, Courtney M; Breaux, Kelly N; Goeders, Nicholas E

    2017-03-01

    We have previously demonstrated that a combination of drugs (i.e., metyrapone and oxazepam) known to attenuate HPA-axis activity effectively decreases cocaine self-administration and cue reactivity in rats. However, we did not find changes in plasma corticosterone that matched the behavioral effects we observed, indicating that a different mechanism of action must be involved. Therefore, we hypothesized that the combination of metyrapone and oxazepam attenuates cocaine taking and seeking by decreasing cocaine-induced increases in corticosterone in the brain. Male rats were implanted with guide cannulae targeting the medial prefrontal cortex or nucleus accumbens. After the rats recovered from surgery, the microdialysis session was conducted. Rats were housed in the experimental chamber and the dialysis probes inserted into the guide cannulae the night before the session. The following day, dialysate samples were collected over a five-hour session. Baseline samples were collected for the first two hours, every 20min. Samples were then collected following administration of cocaine (15mg/kg, ip). Before injections of cocaine, rats were pretreated with either vehicle or the combination of metyrapone (50mg/kg, ip) and oxazepam (10mg/kg, ip). The administration of cocaine resulted in an increase in corticosterone in the medial prefrontal cortex following vehicle pretreatment, which was not observed in the nucleus accumbens. This cocaine-induced increase in corticosterone was attenuated by metyrapone/oxazepam. Reducing cocaine-induced increases in corticosterone in the medial prefrontal cortex might represent a novel mechanism through which the combination of metyrapone/oxazepam produces its behavioral effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

    Science.gov (United States)

    Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

    2010-01-01

    Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

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

    Science.gov (United States)

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

    2014-04-30

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

  12. Increased Entorhinal–Prefrontal Theta Synchronization Parallels Decreased Entorhinal–Hippocampal Theta Synchronization during Learning and Consolidation of Associative Memory

    Science.gov (United States)

    Takehara-Nishiuchi, Kaori; Maal-Bared, Geith; Morrissey, Mark D.

    2012-01-01

    Memories are thought to be encoded as a distributed representation in the neocortex. The medial prefrontal cortex (mPFC) has been shown to support the expression of memories that initially depend on the hippocampus (HPC), yet the mechanisms by which the HPC and mPFC access the distributed representations in the neocortex are unknown. By measuring phase synchronization of local field potential (LFP) oscillations, we found that learning initiated changes in neuronal communication of the HPC and mPFC with the lateral entorhinal cortex (LEC), an area that is connected with many other neocortical regions. LFPs were recorded simultaneously from the three brain regions while rats formed an association between an auditory stimulus (CS) and eyelid stimulation (US) in a trace eyeblink conditioning paradigm, as well as during retention 1 month following learning. Over the course of learning, theta oscillations in the LEC and mPFC became strongly synchronized following presentation of the CS on trials in which rats exhibited a conditioned response (CR), and this strengthened synchronization was also observed during remote retention. In contrast, CS-evoked theta synchronization between the LEC and HPC decreased with learning. Our results suggest that communication between the LEC and mPFC are strengthened with learning whereas the communication between the LEC and HPC are concomitantly weakened, suggesting that enhanced LEC–mPFC communication may be a neuronal correlate for theoretically proposed neocortical reorganization accompanying encoding and consolidation of a memory. PMID:22319482

  13. Increased activity in the right prefrontal cortex measured using near-infrared spectroscopy during a flower arrangement task.

    Science.gov (United States)

    Morita, Yuka; Ebara, Fumio; Morita, Yoshimitsu; Horikawa, Etsuo

    2017-08-21

    Flower arrangement program (FAP) horticultural therapy promotes psychological, social and physiological wellness and recovery. Moreover, FAPs have been used to evaluate the outcomes related to visuospatial working memory; yet, most of these studies used subjective outcome measures such as behavioural observations and questionnaires. Few studies report objective evaluations of FAP effects in humans. In the present study, we measured the effects of an FAP task on frontal lobe activity in healthy participants using near-infrared spectroscopy. We quantified salivary amylase levels as an indicator of stress level during the FAP. The FAP task involved a predetermined arrangement pattern of natural materials (flowers and leaves) that required the participants to identify where a given material should be placed and temporarily memorise the designated position to complete the flower arrangement. The FAP task was compared to the block-tapping task (BTT), which is routinely used to evaluate visuospatial working memory. Both the FAP task and BTT positively stimulated the right prefrontal cortex; however, stress was more effectively limited during the performance of the FAP task. Our data suggest that FAP therapy may be useful for the rehabilitation of patients who are sensitive to stress.

  14. Selective increase of intention-based economic decisions by noninvasive brain stimulation to the dorsolateral prefrontal cortex.

    Science.gov (United States)

    Nihonsugi, Tsuyoshi; Ihara, Aya; Haruno, Masahiko

    2015-02-25

    The intention behind another's action and the impact of the outcome are major determinants of human economic behavior. It is poorly understood, however, whether the two systems share a core neural computation. Here, we investigated whether the two systems are causally dissociable in the brain by integrating computational modeling, functional magnetic resonance imaging, and transcranial direct current stimulation experiments in a newly developed trust game task. We show not only that right dorsolateral prefrontal cortex (DLPFC) activity is correlated with intention-based economic decisions and that ventral striatum and amygdala activity are correlated with outcome-based decisions, but also that stimulation to the DLPFC selectively enhances intention-based decisions. These findings suggest that the right DLPFC is involved in the implementation of intention-based decisions in the processing of cooperative decisions. This causal dissociation of cortical and subcortical backgrounds may indicate evolutionary and developmental differences in the two decision systems. Copyright © 2015 the authors 0270-6474/15/53412-08$15.00/0.

  15. Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release

    DEFF Research Database (Denmark)

    Bortz, D M; Mikkelsen, J D; Bruno, J P

    2013-01-01

    that inhibited (threo-beta-benzyl-oxy-aspartate (TβOA), 100.0μM) or facilitated (ceftriaxalone, 200mg/kg, i.p.) excitatory amino acid transporters. TβOA slowed both the clearance (s) and rate of clearance (μM/s) by 10-fold, particularly at the mid-late stages of the return to baseline. Ceftriaxone reduced......The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels...

  16. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Maurício dos Santos Pereira

    Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

  17. The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity.

    Science.gov (United States)

    Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur

    2017-01-05

    The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT1A/1B-receptor activation decreases impulsive choice, but increases impulsive action. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Structural and Functional Plasticity within the Nucleus Accumbens and Prefrontal Cortex Associated with Time-Dependent Increases in Food Cue-Seeking Behavior.

    Science.gov (United States)

    Dingess, Paige M; Darling, Rebecca A; Derman, Rifka C; Wulff, Shaun S; Hunter, Melissa L; Ferrario, Carrie R; Brown, Travis E

    2017-11-01

    Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling, we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving'). Rats self-administered 60% high fat or chow 45 mg pellets and were then tested for incubation of craving either 1 or 30 days after training. High fat was chosen for comparison to determine whether palatability differentially affected incubation and/or plasticity. Rats showed robust incubation of craving for both food rewards, although responding for cues previously associated with high fat was greater than chow at both 1 and 30 days. In addition, previous experience with high-fat consumption reduced dendritic spine density in the PFC at both time points. In contrast, incubation was associated with an increase in NAc spine density and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission at 30 days in both groups. Finally, incubation of craving for chow and high fat was accompanied by an increase in calcium-permeable and calcium-impermeable AMPARs, respectively. Our results suggest that incubation of food craving alters brain reward circuitry and macronutrient composition specifically induces cortical changes in a way that may facilitate maladaptive food-seeking behaviors.

  19. Administration of thimerosal to infant rats increases overflow of glutamate and aspartate in the prefrontal cortex: protective role of dehydroepiandrosterone sulfate.

    Science.gov (United States)

    Duszczyk-Budhathoki, Michalina; Olczak, Mieszko; Lehner, Malgorzata; Majewska, Maria Dorota

    2012-02-01

    Thimerosal, a mercury-containing vaccine preservative, is a suspected factor in the etiology of neurodevelopmental disorders. We previously showed that its administration to infant rats causes behavioral, neurochemical and neuropathological abnormalities similar to those present in autism. Here we examined, using microdialysis, the effect of thimerosal on extracellular levels of neuroactive amino acids in the rat prefrontal cortex (PFC). Thimerosal administration (4 injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15) induced lasting changes in amino acid overflow: an increase of glutamate and aspartate accompanied by a decrease of glycine and alanine; measured 10-14 weeks after the injections. Four injections of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate and aspartate concentrations at microdialysis time (but based on thimerosal pharmacokinetics, could have been effective soon after its injection). Application of thimerosal to the PFC in perfusion fluid evoked a rapid increase of glutamate overflow. Coadministration of the neurosteroid, dehydroepiandrosterone sulfate (DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate and aspartate; the steroid alone had no influence on these amino acids. Coapplication of DHEAS with thimerosal in perfusion fluid also blocked the acute action of thimerosal on glutamate. In contrast, DHEAS alone reduced overflow of glycine and alanine, somewhat potentiating the thimerosal effect on these amino acids. Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders. DHEAS may partially protect against mercurials-induced neurotoxicity.

  20. 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.

  1. Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress.

    Science.gov (United States)

    Fitzgibbon, Bernadette Mary; Kirkovski, Melissa; Bailey, Neil Wayne; Thomson, Richard Hilton; Eisenberger, Naomi; Enticott, Peter Gregory; Fitzgerald, Paul Bernard

    2017-06-01

    The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the "Cyberball Task"; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.

  2. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control...

  3. Working Memory in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Shintaro Funahashi

    2017-04-01

    Full Text Available 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.

  4. Working Memory in the Prefrontal Cortex.

    Science.gov (United States)

    Funahashi, Shintaro

    2017-04-27

    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.

  5. Higher Heart-Rate Variability Is Associated with Ventromedial Prefrontal Cortex Activity and Increased Resistance to Temptation in Dietary Self-Control Challenges.

    Science.gov (United States)

    Maier, Silvia U; Hare, Todd A

    2017-01-11

    Higher levels of self-control in decision making have been linked to better psychosocial and physical health. A similar link to health outcomes has been reported for heart-rate variability (HRV), a marker of physiological flexibility. Here, we sought to link these two, largely separate, research domains by testing the hypothesis that greater HRV would be associated with better dietary self-control in humans. Specifically, we examined whether total HRV at sedentary rest (measured as the SD of normal-to-normal intervals) can serve as a biomarker for the neurophysiological adaptability that putatively underlies self-controlled behavior. We found that HRV explained a significant portion of the individual variability in dietary self-control, with individuals having higher HRV being better able to downregulate their cravings in the face of taste temptations. Furthermore, HRV was associated with activity patterns in the ventromedial prefrontal cortex (vmPFC), a key node in the brain's valuation and decision circuitry. Specifically, individuals with higher HRV showed both higher overall vmPFC blood-oxygen-level-dependent activity and attenuated taste representations when presented with a dietary self-control challenge. Last, the behavioral and neural associations with HRV were consistent across both our stress induction and control experimental conditions. The stability of this association across experimental conditions suggests that HRV may serve as both a readily obtainable and robust biomarker for self-control ability across environmental contexts. Self-control is associated with better health, but behavioral and psychometric self-control measures allow only indirect associations with health outcomes and may be distorted by reporting bias. We tested whether resting heart-rate variability (HRV), a physiological indicator of psychological and physical health, can predict individual differences in dietary self-control in humans. We found that higher HRV was associated with

  6. Noradrenergic lesion of the locus coeruleus increases the firing activity of the medial prefrontal cortex pyramidal neurons and the role of alpha2-adrenoceptors in normal and medial forebrain bundle lesioned rats.

    Science.gov (United States)

    Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen Hua; Hui, Yan Ping; Wang, Tao; Chen, Li; Li, Qiang

    2010-04-09

    Degeneration of noradrenergic neurons in the locus coeruleus (LC) and dysfunction of the prefrontal cortex were regarded as playing a specific role in the occurrence of non-motor symptoms in Parkinson's disease. The present study examined the spontaneous firing rate and firing pattern of medial prefrontal cortex (mPFC) pyramidal neurons, and effects of alpha(2)-adrenoceptor agonist UK-14,304 and antagonist yohimbine on the neuronal activity in rats with 6-hydroxydopamine lesions of the LC, medial forebrain bundle (MFB) and with combined MFB and LC lesions. The firing rate of mPFC pyramidal neurons in rats with lesions of the LC and with combine LC and MFB lesions is significantly higher than that of normal and MFB-lesioned rats and the firing pattern of these neurons in rats with lesions of the LC and with combine LC and MFB lesions also changed significantly towards more regular compared with normal and MFB-lesioned rats. The local administration of UK-14,304 in the mPFC inhibited the firing activity of the pyramidal neurons in normal rats and rats with lesions of the LC, MFB and with combined LC and MFB lesions, while yohimbine increased the firing activity of the pyramidal neurons. These results indicate that the lesions of the LC lead to hyperactivity of mPFC pyramidal neurons in normal and MFB-lesioned rats, and the postsynaptic alpha(2)-adrenoceptors may partially mediate the inhibitory effects of LC-noradrenergic system on the firing activity of pyramidal neurons in the mPFC, suggesting that LC-noradrenergic system plays an important role in the functional disorders of mPFC in Parkinson's disease. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Magnetoencephalographic signatures of right prefrontal cortex involvement in response inhibition.

    Science.gov (United States)

    Hege, Maike A; Preissl, Hubert; Stingl, Krunoslav T

    2014-10-01

    The prefrontal cortex has a pivotal role in top-down control of cognitive and sensory functions. In complex go-nogo tasks, the right dorsolateral prefrontal cortex is considered to be important for guiding the response inhibition. However, little is known about the temporal dynamics and neurophysiological nature of this activity. To address this issue, we recorded magnetoencephalographic brain activity in 20 women during a visual go-nogo task. The right dorsolateral prefrontal cortex showed an increase for the amplitude of the event-related fields and an increase in induced alpha frequency band activity for nogo in comparison to go trials. The peak of this prefrontal activity preceded the mean reaction time of around 360 ms for go trials, and thus supports the proposed role of right dorsolateral prefrontal cortex in gating the response inhibition and further suggests that right prefrontal alpha band activity might be involved in this gating. However, the results in right dorsolateral prefrontal cortex were similar for both successful and unsuccessful response inhibition. In these conditions, we instead observed pre- and poststimulus differences in alpha band activity in occipital and central areas. Thus, successful response inhibition seemed to additionally depend on prestimulus anticipatory alpha desynchronization in sensory areas as it was reduced prior to unsuccessful response inhibition. In conclusion, we suggest a role for functional inhibition by alpha synchronization not only in sensory, but also in prefrontal areas. Copyright © 2014 Wiley Periodicals, Inc.

  8. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

    Directory of Open Access Journals (Sweden)

    Kjell A Svensson

    2012-05-01

    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  9. 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.

  10. Local activation of metabotropic glutamate receptors inhibits the handling-induced increased release of dopamine in the nucleus accumbens but not that of dopamine or noradrenaline in the prefrontal cortex: comparison with inhibition of ionotropic receptors

    NARCIS (Netherlands)

    Feenstra, M. G.; Botterblom, M. H.; van Uum, J. F.

    1998-01-01

    On-line in vivo microdialysis was used to determine the effects of a 16-min handling period on release of dopamine (DA) in the nucleus accumbens and of DA and noradrenaline (NA) in the medial prefrontal cortex of awake, freely moving rats. DA and NA were determined in one HPLC run. Handling resulted

  11. Prefrontal system dysfunction and credit card debt.

    Science.gov (United States)

    Spinella, Marcello; Yang, Bijou; Lester, David

    2004-10-01

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

  12. Increases in [3H]muscimol and [3H]flumazenil binding in the dorsolateral prefrontal cortex in schizophrenia are linked to α4 and γ2S mRNA levels respectively.

    Directory of Open Access Journals (Sweden)

    Mathieu Verdurand

    Full Text Available GABA(A receptors (GABA(AR are composed of several subunits that determine sensitivity to drugs, synaptic localisation and function. Recent studies suggest that agonists targeting selective GABA(AR subunits may have therapeutic value against the cognitive impairments observed in schizophrenia. In this study, we determined whether GABA(AR binding deficits exist in the dorsolateral prefrontal cortex (DLPFC of people with schizophrenia and tested if changes in GABA(AR binding are related to the changes in subunit mRNAs. The GABA orthosteric and the benzodiazepine allosteric binding sites were assessed autoradiographically using [(3H]Muscimol and [(3H]Flumazenil, respectively, in a large cohort of individuals with schizophrenia (n = 37 and their matched controls (n = 37. We measured, using qPCR, mRNA of β (β1, β2, β3, γ (γ1, γ2, γ2S for short and γ2L for long isoform, γ3 and δ subunits and used our previous measurements of GABA(AR α subunit mRNAs in order to relate mRNAs and binding through correlation and regression analysis.Significant increases in both [(3H]Muscimol (p = 0.016 and [(3H]Flumazenil (p = 0.012 binding were found in the DLPFC of schizophrenia patients. Expression levels of mRNA subunits measured did not show any significant difference in schizophrenia compared to controls. Regression analysis revealed that in schizophrenia, the [(3H]Muscimol binding variance was most related to α4 mRNA levels and the [(3H]Flumazenil binding variance was most related to γ2S subunit mRNA levels. [(3H]Muscimol and [(3H]Flumazenil binding were not affected by the lifetime anti-psychotics dose (chlorpromazine equivalent.We report parallel increases in orthosteric and allosteric GABA(AR binding sites in the DLPFC in schizophrenia that may be related to a "shift" in subunit composition towards α4 and γ2S respectively, which may compromise normal GABAergic modulation and function. Our results may have implications for the

  13. The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity

    NARCIS (Netherlands)

    Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur

    2016-01-01

    The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase

  14. 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 patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

  15. Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

    Science.gov (United States)

    McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

    2014-01-01

    Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis

  16. Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

    Science.gov (United States)

    Dahmani, Louisa; Bohbot, Véronique D

    2015-01-01

    The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-11-02

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

  18. Alcohol and the prefrontal cortex.

    Science.gov (United States)

    Abernathy, Kenneth; Chandler, L Judson; Woodward, John J

    2010-01-01

    The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Prefrontal-Subcortical Pathways Mediating Successful Emotion Regulation

    National Research Council Canada - National Science Library

    Wager, Tor D; Davidson, Matthew L; Hughes, Brent L; Lindquist, Martin A; Ochsner, Kevin N

    2008-01-01

    ... regulation of emotion ( Davidson, 2002; Ochsner and Gross, 2005 ). Numerous fMRI studies have observed increases in activity in the ventrolateral, dorsolateral, and dorsomedial prefrontal cortices (vlPFC, dlPFC, and dmPFC, respectively) when participants are instructed to deploy cognitive strategies that reduce negative emotional experience ( Ochsner...

  20. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

    NARCIS (Netherlands)

    Crunelle, Cleo L.; Kaag, Anne Marije; van den Munkhof, Hanna E.; Reneman, Liesbeth; Homberg, Judith R.; Sabbe, Bernard; van den Brink, Wim; van Wingen, Guido

    2015-01-01

    Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal

  1. Bilinearity, rules, and prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Peter Dayan

    2007-11-01

    Full Text Available Humans can be instructed verbally to perform computationally complex cognitive tasks; their performance then improves relatively slowly over the course of practice. Many skills underlie these abilities; in this paper, we focus on the particular question of a uniform architecture for the instantiation of habitual performance and the storage, recall, and execution of simple rules. Our account builds on models of gated working memory, and involves a bilinear architecture for representing conditional input-output maps and for matching rules to the state of the input and working memory. We demonstrate the performance of our model on two paradigmatic tasks used to investigate prefrontal and basal ganglia function.

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

    Directory of Open Access Journals (Sweden)

    Hannah J Foy

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

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

  5. Paired-housing selectively facilitates within-session extinction of avoidance behavior, and increases c-Fos expression in the medial prefrontal cortex, in anxiety vulnerable Wistar-Kyoto rats.

    Science.gov (United States)

    Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D

    2016-10-01

    The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair

  6. The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients

    Directory of Open Access Journals (Sweden)

    Qiao J

    2016-09-01

    Full Text Available Jun Qiao,1,2 Guixing Jin,1,2 Licun Lei,3 Lan Wang,1,2 Yaqiang Du,3 Xueyi Wang1,2 1Institute of Mental Health, The First Hospital of Hebei Medical University, 2Brain Ageing and Cognitive Neuroscience Laboratory, Hebei Medical University, 3Department of Radiology, The First Hospital of Hebei Medical University, Hebei, People’s Republic of China Objective: To explore the effect of right dorsolateral prefrontal cortex (DLPFC repetitive transcranial magnetic stimulation (rTMS on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy (1H-MRS in recently detoxified alcohol-dependent patients. Materials and methods: In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions and the control group (sham stimulation. Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R and Brief Visuospatial Memory Test-Revised (BVMT-R before and after treatment. 1H-MRS was used to detect the levels of N-acetyl aspartic acid (NAA, choline (Cho, and creatine (Cr in bilateral hippocampi before and after treatment. Results: Thirty-eight patients (18 in the experimental group and 20 in the control group were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. Conclusion: High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1H-MRS in recently detoxified alcohol-dependent patients. Keywords: alcohol dependence, memory, repetitive transcranial magnetic stimulation, MR spectroscopy

  7. Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons.

    Directory of Open Access Journals (Sweden)

    Olga Gajewska-Woźniak

    Full Text Available The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c-interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG. LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models

  8. The contribution of the dorsolateral prefrontal cortex to the preparation for deception and truth-telling.

    Science.gov (United States)

    Ito, Ayahito; Abe, Nobuhito; Fujii, Toshikatsu; Hayashi, Akiko; Ueno, Aya; Mugikura, Shunji; Takahashi, Shoki; Mori, Etsuro

    2012-06-29

    Recent neuroimaging evidence suggests that the dorsolateral prefrontal cortex is associated with creating deceptive responses. However, the neural basis of the preparatory processes that create deception has yet to be explored. Previous neuroimaging studies have demonstrated that the preparation for a certain task activates brain areas relevant to the execution of that task, leading to the question of whether dorsolateral prefrontal activity is observed during the preparation for deception. In the present study, we used functional magnetic resonance imaging (fMRI) to determine whether dorsolateral prefrontal activity, which increases during the execution of deception compared with the execution of truth-telling, also increases during the preparation for deception compared with the preparation for truth-telling. Our data show that the execution of deception was associated with increased activity in several brain regions, including the left dorsolateral prefrontal cortex, compared with truth-telling, confirming the contribution of this region to the production of deceptive responses. The results also reveal that the preparations for both deception and truth-telling were associated with increased activity in certain brain regions, including the left dorsolateral prefrontal cortex. These findings suggest that the preparations for truth-telling and deception make similar demands on the brain and that the dorsolateral prefrontal activity identified in the preparation phase is associated with general preparatory processes, regardless of whether one is telling a lie or the truth. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Teasaponin improves leptin sensitivity in the prefrontal cortex of obese mice.

    Science.gov (United States)

    Yu, Yinghua; Wu, Yizhen; Szabo, Alexander; Wang, Sen; Yu, Shijia; Wang, Qing; Huang, Xu-Feng

    2015-12-01

    Obesity impairs cognition, and the leptin-induced increase of brain-derived neurotrophic factor (BDNF) and neurogenesis. Tea consumption improves cognition and increases brain activation in the prefrontal cortex. This study examined whether teasaponin, an active ingredient in tea, could improve memory and central leptin effects on neurogenesis in the prefrontal cortex of obese mice, and in vitro in cultured prefrontal cortical neurons. Teasaponin (10 mg/kg, intraperitoneal) for 21 days improved downstream leptin signaling (JAK2 and STAT3), and leptin's effect on BDNF, in the prefrontal cortex of high-fat diet (HFD) fed mice. Prefrontal cortical neurons were cultured with teasaponin and palmitic acid (the most abundant dietary saturated fatty acid) to examine their effects on neurogenesis and BDNF expression in response to leptin. Palmitic acid decreased leptin's effect on neurite outgrowth, postsynaptic density protein 95, and BDNF expression in cultured cortical neurons, which was reversed by teasaponin. Teasaponin improved the leptin sensitivity of prefrontal cortical neurons in obese mice or when treated by palmitic acid. This in turn increased BDNF expression and neurite growth. Therefore, teasaponin supplementation may be used to prevent obesity-associated neurodegeneration and improve cognitive function. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2016-06-01

    Although deep brain stimulation (DBS) has been used with success in treatment-resistant depression, little is known about its mechanism of action. We examined the antidepressant-like activity of short (1 h) DBS applied to the infralimbic prefrontal cortex in the forced swim test (FST) and the novelty-suppressed feeding test (NSFT). We also used in vivo microdialysis to evaluate the release of glutamate, γ-aminobutyric acid, serotonin, dopamine, and noradrenaline in the prefrontal cortex and c-Fos immunohistochemistry to determine the brain regions activated by DBS. One hour of DBS of the infralimbic prefrontal cortex has antidepressant-like effects in FST and NSFT, and increases prefrontal efflux of glutamate, which would activate AMPA receptors (AMPARs). This effect is specific of the infralimbic area since it is not observed after DBS of the prelimbic subregion. The activation of prefrontal AMPARs would result in a stimulation of prefrontal output to the brainstem, thus increasing serotonin, dopamine, and noradrenaline in the prefrontal cortex. Further, the activation of prefrontal AMPARs is necessary and sufficient condition for the antidepressant response of 1 h DBS. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Prefrontal EEG correlation during Tower of Hanoi and WCST performance: effect of emotional visual stimuli.

    Science.gov (United States)

    Ruiz-Díaz, Marina; Hernández-González, Marisela; Guevara, Miguel Angel; Amezcua, Claudia; Ågmo, Anders

    2012-10-01

    Emotional stimuli elicit changes in the electroencephalographic (EEG) activity of several brain structures. Prefrontal cortex is involved in the processing of emotional stimuli and executive functions. The correlation analysis of EEG provides information about the functional coupling between areas. It is reasonable to expect that emotional activation will modify prefrontal coupling during the performance of executive tasks such as Tower of Hanoi or Wisconsin Card Sorting Test (WCST). Determine whether the prefrontal EEG correlation during the performance of the Tower of Hanoi and WCST is affected by previous exposure to videos with sexual or aggressive content. Prefrontal EEG coupling was determined by the Pearson correlation. Valence and general arousal were evaluated by the Self-Assessment Manikin Scale and sexual arousal with a Sexual Arousal Scale. Computerized versions of the Towers of Hanoi and WCST provided data on prefrontal executive functions. EEG from the left and right prefrontal zones was recorded during the performance of the Tower of Hanoi and WCST immediately after the subjects were exposed to one of the videos (neutral, aggressive, and erotic). There was no difference between videos in the task performance parameters. Only the erotic video produced an increased prefrontal coupling in the slow bands (delta and theta) during the performance of the Tower of Hanoi, whereas a decreased coupling in the delta, theta, and alpha bands was observed during the WCST. Prefrontal coupling was changed after exposure to the erotic video, and it is likely that enhanced sexual arousal was the main cause of this change. The correlation patterns obtained could be associated with particular cognitive strategies or to functional adaptations while being sexually aroused. The results of this study may contribute to an understanding of the central nervous mechanisms underlying the cognitive effects of sexual arousal. © 2012 International Society for Sexual Medicine.

  12. Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

    Science.gov (United States)

    Glasper, Erica R; LaMarca, Elizabeth A; Bocarsly, Miriam E; Fasolino, Maria; Opendak, Maya; Gould, Elizabeth

    2015-11-01

    The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this performance decrement, chronic stress reduces the number of dendritic spines on pyramidal neurons in the medial prefrontal cortex. No previous studies have examined whether a rewarding experience, namely mating, affects cognitive flexibility and dendritic spines in the medial prefrontal cortex of male rats. To test this possibility, we exposed adult male rats to sexual receptive females once daily for one week, assessed attentional set-shifting performance, and then analyzed their brains for changes in dendritic spines. We found that sexual experience improved performance on extradimensional set-shifting, which is known to require the medial prefrontal cortex. Additionally, we observed increased dendritic spine density on apical and basal dendrites of pyramidal neurons in the medial prefrontal cortex, but not the orbitofrontal cortex, after sexual experience. We also found that sexual experience enhanced dendritic spine density on granule neurons of the dentate gyrus. The ventral hippocampus sends a direct projection to the medial prefrontal cortex, raising the possibility that experience-dependent changes in the hippocampus are necessary for alterations in medial prefrontal cortex structure and function. As a first attempt at investigating this, we inactivated the ventral hippocampus with the GABA agonist muscimol, after each daily bout of sexual experience to observe whether the beneficial effects on cognitive flexibility were abolished. Contrary to our hypothesis, blocking hippocampal activity after sexual experience had no impact on enhanced cognitive flexibility. Taken together, these findings indicate that sexual

  13. Exceptional Evolutionary Expansion of Prefrontal Cortex in Great Apes and Humans.

    Science.gov (United States)

    Smaers, Jeroen B; Gómez-Robles, Aida; Parks, Ashley N; Sherwood, Chet C

    2017-03-06

    One of the enduring questions that has driven neuroscientific enquiry in the last century has been the nature of differences in the prefrontal cortex of humans versus other animals [1]. The prefrontal cortex has drawn particular interest due to its role in a range of evolutionarily specialized cognitive capacities such as language [2], imagination [3], and complex decision making [4]. Both cytoarchitectonic [5] and comparative neuroimaging [6] studies have converged on the conclusion that the proportion of prefrontal cortex in the human brain is greatly increased relative to that of other primates. However, considering the tremendous overall expansion of the neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal enlargement follows general allometric growth patterns, or whether it is exceptional [1]. Species' adherence to a common allometric relationship suggests conservation through phenotypic integration, while species' deviations point toward the occurrence of shifts in genetic and/or developmental mechanisms. Here we investigate prefrontal cortex scaling across anthropoid primates and find that great ape and human prefrontal cortex expansion are non-allometrically derived features of cortical organization. This result aligns with evidence for a developmental heterochronic shift in human prefrontal growth [7, 8], suggesting an association between neurodevelopmental changes and cortical organization on a macroevolutionary scale. The evolutionary origin of non-allometric prefrontal enlargement is estimated to lie at the root of great apes (∼19-15 mya), indicating that selection for changes in executive cognitive functions characterized both great ape and human cortical organization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Auditory Connections and Functions of Prefrontal Cortex

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    Bethany ePlakke

    2014-07-01

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

  15. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

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

  16. Human ventromedial prefrontal lesions alter incentivisation by reward.

    Science.gov (United States)

    Manohar, Sanjay G; Husain, Masud

    2016-03-01

    Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Adrenergic Pharmacology and Cognition: Focus on the Prefrontal Cortex

    Science.gov (United States)

    Ramos, Brian P.; Arnsten, Amy F.T.

    2007-01-01

    Norepinephrine (NE) has widespread projections throughout brain, and thus is ideally positioned to orchestrate neural functions based on arousal state. For example, NE can increase “signal/noise” ratio in the processing of sensory stimuli, and can enhance long-term memory consolidation in the amygdala and hippocampus through actions at α-1 and β adrenoceptors. Over the last 20 years, NE has also been shown to play a powerful role in regulating the working memory and attention functions of the prefrontal cortex (PFC). Moderate levels of NE released under control conditions strengthen prefrontal cortical functions via actions at post-synaptic α-2A adrenoceptors with high affinity for NE, while high levels of NE release during stress impair PFC cortical functions via α-1 and possibly β-1 receptors with lower affinity for NE. Thus, levels of NE determine whether prefrontal cortical or posterior cortical systems control our behavior and thought. Understanding these receptor mechanisms has led to new, intelligent treatments for neuropsychiatric disorders associated with PFC dysfunction. PMID:17303246

  18. Brain injury impairs working memory and prefrontal circuit function

    Directory of Open Access Journals (Sweden)

    Colin James Smith

    2015-11-01

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

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

    Science.gov (United States)

    Ray, Rebecca; Zald, David H.

    2011-01-01

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

  20. Differential prefrontal response to infant facial emotions in mothers compared with non-mothers.

    Science.gov (United States)

    Nishitani, Shota; Doi, Hirokazu; Koyama, Atsuko; Shinohara, Kazuyuki

    2011-06-01

    A considerable body of research has focused on neural responses evoked by emotional facial expressions, but little is known about mother-specific brain responses to infant facial emotions. We used near-infrared spectroscopy to investigate prefrontal activity during discriminating facial expressions of happy, angry, sad, fearful, surprised and neutral of unfamiliar infants and unfamiliar adults by 14 mothers and 14 age-matched females who have never been pregnant (non-mothers). Our results revealed that discriminating infant facial emotions increased the relative oxyHb concentration in mothers' right prefrontal cortex but not in their left prefrontal cortex, compared with each side of the prefrontal cortices of non-mothers. However, there was no difference between mothers and non-mothers in right or left prefrontal cortex activation while viewing adult facial expressions. These results suggest that the right prefrontal cortex is involved in human maternal behavior concerning infant facial emotion discrimination. Crown Copyright © 2011. Published by Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  1. Prefrontal control of attention to threat

    Directory of Open Access Journals (Sweden)

    Polly V Peers

    2013-02-01

    Full Text Available Attentional control refers to the regulatory processes that ensure that our actions are in accordance with our goals. Dual-system accounts view temperament as consisting of both individual variation in emotionality (e.g. trait anxiety and variation in regulatory attentional mechanisms that act to modulate emotionality. Increasing evidence links trait variation in attentional control to clinical mood and anxiety disorder symptoms, independent of trait emotionality. Attentional biases to threat have been robustly linked to mood and anxiety disorders. However, the role of variation in attentional control in influencing such biases, and the neural underpinnings of trait variation in attentional control, are unknown. Here, we show, that individual differences in trait attentional control, even when accounting for trait and state anxiety, are related to the magnitude of an attentional blink following threat-related targets. Moreover, we demonstrate that activity in dorsolateral prefrontal cortex, is observed specifically in relation to control of attention over threatening stimuli, in line with neural theories of attentional control, such as guided activation theory. These results have key implications for neurocognitive theories of attentional bias and emotional resilience.

  2. [Prefrontal cortex in memory and attention processes].

    Science.gov (United States)

    Allegri, R F; Harris, P

    The role of the prefrontal cortex still remains poorly understood. Only after 1970, the functions of the frontal lobes have been conceptualized from different points of view (behaviorism, cognitivism). Recently,different parallel circuits connecting discrete cortical and subcortical regions of the frontal lobes have been described. Three of these circuits are the most relevant to understanding of behavior: the dorsolateral prefrontal circuit, that mediates executive behavior; the orbitofrontal prefrontal circuit, mediating social behavior, and the medial frontal circuit, involved in motivation. Damage to the frontal cortex impairs planning, problem solving, reasoning, concept formation, temporal ordering of stimuli, estimation, attention, memory search, maintaining information in working memory, associative learning,certain forms of skilled motor activities, image generation and manipulation of the spatial properties of a stimulus, metacognitive thinking, and social cognition. Several theories have been proposed to explain the functions of the prefrontal cortex. Currently,the most influential cognitive models are: the Norman and Shallice supervisory attentional system, involved in non-routine selection; the Baddeley working memory model with the central executive as a supervisory controlling system, in which impairment leads to a 'dysexecutive syndrome'; and the Grafman's model of managerial knowledge units, stored as macrostructured information in the frontal cortex. The prefrontal cortex is essential for attentional control, manipulation of stored knowledge and modulation of complex actions, cognition, emotion and behavior.

  3. Disruption of columnar and laminar cognitive processing in primate prefrontal cortex following cocaine exposure

    Directory of Open Access Journals (Sweden)

    Ioan eOpris

    2015-05-01

    Full Text Available Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs were trained in a visual delayed match-to-sample (DMS task while the activity of prefrontal cortical neurons (areas 46, 8 and 6 was recorded simultaneously with a custom multielectrode array in cell layers 2/3 and 5. Animals were reinforced with juice for correct responses. The first half of the recording session (control was conducted following saline injection and in the second half of the same session cocaine was administered. Prefrontal neuron activity with respect to inter- and intra-laminar firing in layers 2/3 and 5 was assessed in the DMS task before and after the injection of cocaine. Results showed that firing rates of both pyramidal cells and interneurons increased on Match phase presentation and the Match response in both control and cocaine halves of the session. Differential firing under cocaine vs. control in the Match phase was increased for interneurons but decreased for pyramidal cells. In addition, functional` interactions between prefrontal pyramidal cells in layer 2/3 and 5 decreased while intra-laminar cross-correlations in both layers increased. These neural recordings demonstrate that prefrontal neurons differentially encode and process information within and between cortical cell layers via cortical columns which is disrupted in a differential manner by cocaine administration.

  4. 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

  5. Sensitive Dependence of Mental Function on Prefrontal Cortex

    OpenAIRE

    Alen J Salerian

    2015-01-01

    This study offers evidence to suggest that both normalcy and psychiatric illness are sensitively dependent upon prefrontal cortex function. In general, the emergence of psychiatric symptoms coincide with diminished influence of prefrontal cortex function. The mediating influence of prefrontal cortex may be independent of molecular and regional brain dysfunctions contributory to psychiatric illness.

  6. Medial Prefrontal Cortex Updates Its Status.

    Science.gov (United States)

    Cikara, Mina; Gershman, Samuel J

    2016-12-07

    How does the brain infer social status? A new study by Kumaran et al. (2016) identifies a region of the medial prefrontal cortex that, in concert with the amygdala and hippocampus, subserves updating of probabilistic beliefs about the status of individuals in a social hierarchy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

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

    2014-08-01

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

  8. Neural modeling of prefrontal executive function

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

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

  9. Developmental Outcomes after Early Prefrontal Cortex Damage

    Science.gov (United States)

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

    2004-01-01

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

  10. Representation of remembered stimuli and task information in the monkey dorsolateral prefrontal and posterior parietal cortex.

    Science.gov (United States)

    Qi, Xue-Lian; Elworthy, Anthony C; Lambert, Bryce C; Constantinidis, Christos

    2015-01-01

    Both dorsolateral prefrontal and posterior parietal cortex have been implicated in spatial working memory and representation of task information. Prior experiments training animals to recall the first of a sequence of stimuli and examining the effect of subsequent distractors have identified increased ability of the prefrontal cortex to represent remembered stimuli and filter distractors. It is unclear, however, if this prefrontal functional specialization extends to stimuli appearing earlier in a sequence, when subjects are cued to remember subsequent ones. It is also not known how task information interacts with persistent activity representing remembered stimuli and distractors in the two areas. To address these questions, we trained monkeys to remember either the first or second of two stimuli presented in sequence and recorded neuronal activity from the posterior parietal and dorsolateral prefrontal cortex. The prefrontal cortex was better able to represent the actively remembered stimulus, whereas the posterior parietal cortex was more modulated by distractors; however, task effects interfered with this representation. As a result, large proportions of neurons with persistent activity and task effects exhibited a preference for a stimulus when it appeared as a distractor in both areas. Additionally, prefrontal neurons were modulated to a greater extent by task factors during the delay period of the task. The results indicate that the prefrontal cortex is better able than the posterior parietal cortex to differentiate between distractors and actively remembered stimuli and is more modulated by the task; however, this relative preference is highly context dependent and depends on the specific requirements of the task. Copyright © 2015 the American Physiological Society.

  11. Enhanced Neuronal Activity in the Medial Prefrontal Cortex during Social Approach Behavior.

    Science.gov (United States)

    Lee, Eunee; Rhim, Issac; Lee, Jong Won; Ghim, Jeong-Wook; Lee, Seungjoon; Kim, Eunjoon; Jung, Min Whan

    2016-06-29

    Although the medial prefrontal cortex (mPFC) is known to play a crucial role in rodent social behavior, little is known about mPFC neural correlates of social behavior. In the present study, we examined single-neuron activity in the mPFC of mice performing a modified version of the three-chamber test. We found that a subset of mPFC neurons elevate discharge rates when approaching a stranger mouse but not when approaching an inanimate object or an empty chamber. Our results reveal mPFC neural activity that is correlated with social approach behavior in a widely used social-interaction paradigm. These findings might be helpful for future investigations of mPFC neural processes underlying social interaction in health and disease. Although the prefrontal cortex is known to play a crucial role in rodent social behavior, little is known about prefrontal neural correlates of social behavior. This study shows that the activity of a subset of prefrontal neurons increases in association with social approach behavior during a three-chamber test-a widely used behavioral paradigm. Such responses might be a signature of prefrontal neural processes underlying social approach behavior. Copyright © 2016 the authors 0270-6474/16/366926-11$15.00/0.

  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. Prefrontal-hippocampal dynamics involved in learning regularities across episodes.

    Science.gov (United States)

    Doeller, Christian F; Opitz, Bertram; Krick, Christoph M; Mecklinger, Axel; Reith, Wolfgang

    2005-08-01

    Using functional magnetic resonance imaging, the neural correlates of context-specific memories and invariant memories about regularities across episodes were investigated. Volunteers had to learn conjunctions between objects and positions. In an invariant learning condition, positions were held constant, enabling subjects to learn regularities across trials. By contrast, in a context-specific condition object-position conjunctions were trial unique. Performance increase in the invariant learning condition was paralleled by a learning-related increase of inferior frontal gyrus activation and ventral striatal activation and a decrease of hippocampus activation. Conversely, in the context-specific condition hippocampal activation was constant across trials. We argue that the learning-related hippocampal activation pattern might be due to reduced relational binding requirements once regularities are extracted. Furthermore, we propose that the learning-related prefrontal modulation reflects the requirement to extract and maintain regularities across trials and the adjustment of object-position conjunctions on the basis of the extracted knowledge. Finally, our data suggest that the ventral striatum encodes the increased predictability of spatial features as a function of learning. Taken together, these results indicate a transition of the relative roles of distinct brain regions during learning regularities across multiple episodes: regularity learning is characterized by a shift from a hippocampal to a prefrontal-striatal brain system.

  14. Multiple effects of prefrontal lesions on task-switching

    Directory of Open Access Journals (Sweden)

    Tim Shallice

    2008-03-01

    Full Text Available This study examined the performance of 41 patients with focal prefrontal cortical lesions and 38 healthy controls on a task-switching procedure. Three different conditions were evaluated: single tasks without switches and two switching tasks with the currently relevant task signalled either 1500 ms (Long Cue or 200 ms (Short Cue before the stimulus. Patients with Superior Medial lesions showed both a general slowing of reaction time (RT and a signifi cantly increased switch cost as measured by RT. No other prefrontal group showed this increased reaction time switch cost. Increased error rates in the switching conditions, on the other hand, were observed in patients with Inferior Medial lesions and, to a lesser extent, ones with Superior Medial lesions. Patients with left dorsolateral lesions (9/46v showed slower learning of the task as indicated by a high error rate early on. Several different processes are involved in task-switching and these are selectively disrupted by lesions to specifi c areas of the frontal lobes.

  15. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    OpenAIRE

    Gaelle eDominguez; Pierre eFaucher; Nadia eHenkous; Ali eKrazem; Christophe ePierard; Daniel eBeracochea

    2014-01-01

    Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1...

  16. Prefrontal mediation of age differences in cognitive reappraisal.

    Science.gov (United States)

    Opitz, Philipp C; Rauch, Lindsay C; Terry, Douglas P; Urry, Heather L

    2012-04-01

    Despite cognitive and physical declines, it has been suggested that older adults remain able to regulate their emotions effectively. However, whether this is true for all emotion regulation processes has not been established. We hypothesized that cognitive reappraisal, a form of emotion regulation requiring intact cognitive control ability, may be compromised in older age, and that this age difference would be mediated by reduced activation in prefrontal cortex (PFC). Sixteen younger and 15 older adults used gaze-directed reappraisal to increase and decrease emotion in response to unpleasant pictures. This was compared with simply viewing the pictures. Relative to younger adults, older adults were less successful using reappraisal to decrease unpleasant emotion but more successful using reappraisal to increase unpleasant emotion. They also exhibited reduced activation in dorsomedial and left ventrolateral prefrontal cortex. Importantly, activation in these regions differentially mediated the effect of age on emotion. This pattern confirms the importance of cognitive control in reappraising unpleasant situations and suggests that older age may (but does not always) confer effective emotion regulation. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Role of prefrontal cortical calcium-independent phospholipase A2 in antinociceptive effect of the norepinephrine reuptake inhibitor antidepresssant maprotiline.

    Science.gov (United States)

    Chew, Wee-Siong; Shalini, Suku-Maran; Torta, Federico; Wenk, Markus R; Stohler, Christian; Yeo, Jin-Fei; Herr, Deron R; Ong, Wei-Yi

    2017-01-06

    The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A2 (iPLA2) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, maprotiline. Intraperitoneal injections of maprotiline increased iPLA2 mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of maprotiline was abrogated by iPLA2 antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA2 antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in maprotiline-treated mice that received iPLA2 antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA2 and its enzymatic products in the antinociceptive effect of maprotiline. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. 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

  19. Saccades and prefrontal hemodynamics in basketball players.

    Science.gov (United States)

    Fujiwara, K; Kiyota, N; Maekawa, M; Kunita, K; Kiyota, T; Maeda, K

    2009-09-01

    We investigated saccade performance and prefrontal hemodynamics in basketball players with different skill levels. Subjects were 27 undergraduate basketball players and 13 non-athlete undergraduates (control group: CON). The players were divided into two groups: those who had played in the National Athletic Meet during high school or played regularly (n=13, elite group: ELI) and those who were bench warmers (n=14, skilled group: SKI). Horizontal eye movement and oxy-, deoxy-, and total-hemoglobin (Hb) concentration in the prefrontal cortex during pro- and anti-saccade were measured using electro-oculography and near-infrared spectroscopy, respectively. Only error rate in anti-saccade was less in ELI (4.8+/-4.0%) than SKI (13.7+/-12.6%) and CON (13.9+/-8.3%) (pbasketball. Georg Thieme Verlag KG Stuttgart.

  20. Finding prefrontal cortex in the rat.

    Science.gov (United States)

    Leonard, Christiana M

    2016-08-15

    The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink-Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat׳s MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat׳s MD-projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. © 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B

  1. Specialized prefrontal auditory fields: organization of primate prefrontal-temporal pathways

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    Maria eMedalla

    2014-04-01

    Full Text Available No other modality is more frequently represented in the prefrontal cortex than the auditory, but the role of auditory information in prefrontal functions is not well understood. Pathways from auditory association cortices reach distinct sites in the lateral, orbital, and medial surfaces of the prefrontal cortex in rhesus monkeys. Among prefrontal areas, frontopolar area 10 has the densest interconnections with auditory association areas, spanning a large antero-posterior extent of the superior temporal gyrus from the temporal pole to auditory parabelt and belt regions. Moreover, auditory pathways make up the largest component of the extrinsic connections of area 10, suggesting a special relationship with the auditory modality. Here we review anatomic evidence showing that frontopolar area 10 is indeed the main frontal auditory field as the major recipient of auditory input in the frontal lobe and chief source of output to auditory cortices. Area 10 is thought to be the functional node for the most complex cognitive tasks of multitasking and keeping track of information for future decisions. These patterns suggest that the auditory association links of area 10 are critical for complex cognition. The first part of this review focuses on the organization of prefrontal-auditory pathways at the level of the system and the synapse, with a particular emphasis on area 10. Then we explore ideas on how the elusive role of area 10 in complex cognition may be related to the specialized relationship with auditory association cortices.

  2. Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.

    Science.gov (United States)

    Sajja, Venkata Siva Sai Sujith; Perrine, Shane A; Ghoddoussi, Farhad; Hall, Christina S; Galloway, Matthew P; VandeVord, Pamela J

    2014-03-01

    Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Kamiya, Kazunobu; Narita, Noriyuki; Iwaki, Sunao

    2016-01-01

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

  4. Efficiency of the Prefrontal Cortex during Working Memory in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Sheridan, Margaret A.; Hinshaw, Stephen; D'Esposito, Mark

    2007-01-01

    Objective: Previous research has demonstrated that during task conditions requiring an increase in inhibitory function or working memory, children and adults with attention-deficit/hyperactivity disorder (ADHD) exhibit greater and more varied prefrontal cortical(PFC) activation compared to age-matched control participants. This pattern may reflect…

  5. Decrease of Prefrontal-Posterior EEG Coherence: Loose Control during Social-Emotional Stimulation

    Science.gov (United States)

    Reiser, Eva M.; Schulter, Gunter; Weiss, Elisabeth M.; Fink, Andreas; Rominger, Christian; Papousek, Ilona

    2012-01-01

    In two experiments we aimed to investigate if individual differences in state-dependent decreases or increases of EEG coherence between prefrontal and posterior cortical regions may be indicative of a mechanism modulating the impact social-emotional information has on an individual. Two independent samples were exposed to an emotional stimulation…

  6. Effect of a pharmacological stressor on glutamate efflux in the prefrontal cortex

    NARCIS (Netherlands)

    Karreman, M; Moghaddam, B

    1996-01-01

    The anxiogenic beta-carboline, FG 7142 (20 mg/kg) significantly increased glutamate efflux in the prefrontal cortex of conscious rats as assessed by microdialysis. Pretreatment with the benzodiazepine receptor agonist, diazepam (5 mg/kg), abolished this effect. These findings indicate that

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

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    Singh eDeepeshwar

    2015-02-01

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

  8. Prefrontal engagement by cognitive reappraisal of negative faces.

    Science.gov (United States)

    Nelson, Brady D; Fitzgerald, Daniel A; Klumpp, Heide; Shankman, Stewart A; Phan, K Luan

    2015-02-15

    Cognitive reappraisal has been associated with increased activation in prefrontal cortex (PFC) and cingulate regions implicated in cognitive control and affect regulation. To date, neuroimaging studies of reappraisal have primarily used emotionally evocative scenes, and it remains unclear whether the same cognitive strategy applied to emotional facial expressions would involve similar or different neural underpinnings. The present study used fMRI to examine brain activation during cognitive reappraisal of negatively valenced facial expressions relative to passive viewing of negative and neutral facial expressions. Twenty-two healthy adults completed a cognitive reappraisal task comprised of three different conditions (Look-Neutral, Maintain-Negative, Reappraise-Negative). Results indicated that reappraisal was associated with a decrease in negative affect and engagement of PFC brain regions implicated in cognitive control and affect regulation (DLPFC, mPFC, and VLPFC). Furthermore, individual differences in habitual reappraisal use were associated with greater DLPFC and mPFC activation, while suppression use was associated with greater amygdala activation. The present study provides preliminary evidence that facial expressions are effective alternative 'targets' of prefrontal engagement during cognitive reappraisal. These findings are particularly relevant for future research probing the neural bases of emotion regulation in populations for whom aversive scenes may be less appropriate (e.g., children) and illnesses in which aberrant responses to social signals of threat and negative feedback are cardinal phenotypes. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 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.

  10. 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

  11. Prefrontal Contribution to Decision-Making under Free-Choice Conditions

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    Shintaro Funahashi

    2017-07-01

    Full Text Available Executive function is thought to be the coordinated operation of multiple neural processes and allows to accomplish a current goal flexibly. The most important function of the prefrontal cortex is the executive function. Among a variety of executive functions in which the prefrontal cortex participates, decision-making is one of the most important. Although the prefrontal contribution to decision-making has been examined using a variety of behavioral tasks, recent studies using fMRI have shown that the prefrontal cortex participates in decision-making under free-choice conditions. Since decision-making under free-choice conditions represents the very first stage for any kind of decision-making process, it is important that we understand its neural mechanism. Although few studies have examined this issue while a monkey performed a free-choice task, those studies showed that, when the monkey made a decision to subsequently choose one particular option, prefrontal neurons showing selectivity to that option exhibited transient activation just before presentation of the imperative cue. Further studies have suggested that this transient increase is caused by the irregular fluctuation of spontaneous firing just before cue presentation, which enhances the response to the cue and biases the strength of the neuron's selectivity to the option. In addition, this biasing effect was observed only in neurons that exhibited sustained delay-period activity, indicating that this biasing effect not only influences the animal's decision for an upcoming choice, but also is linked to working memory mechanisms in the prefrontal cortex.

  12. Prefrontal Contribution to Decision-Making under Free-Choice Conditions

    Science.gov (United States)

    Funahashi, Shintaro

    2017-01-01

    Executive function is thought to be the coordinated operation of multiple neural processes and allows to accomplish a current goal flexibly. The most important function of the prefrontal cortex is the executive function. Among a variety of executive functions in which the prefrontal cortex participates, decision-making is one of the most important. Although the prefrontal contribution to decision-making has been examined using a variety of behavioral tasks, recent studies using fMRI have shown that the prefrontal cortex participates in decision-making under free-choice conditions. Since decision-making under free-choice conditions represents the very first stage for any kind of decision-making process, it is important that we understand its neural mechanism. Although few studies have examined this issue while a monkey performed a free-choice task, those studies showed that, when the monkey made a decision to subsequently choose one particular option, prefrontal neurons showing selectivity to that option exhibited transient activation just before presentation of the imperative cue. Further studies have suggested that this transient increase is caused by the irregular fluctuation of spontaneous firing just before cue presentation, which enhances the response to the cue and biases the strength of the neuron's selectivity to the option. In addition, this biasing effect was observed only in neurons that exhibited sustained delay-period activity, indicating that this biasing effect not only influences the animal's decision for an upcoming choice, but also is linked to working memory mechanisms in the prefrontal cortex. PMID:28798662

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Asymmetric activation in the prefrontal cortex by sound-induced affect.

    Science.gov (United States)

    Kim, Wuon-Shik; Yoon, Young-Ro; Kim, Kyo-Heon; Jho, Moon-Jae; Lee, Sang-Tae

    2003-12-01

    This study is based on previous information regarding asymmetric activation in the prefrontal cortex by film-induced affects, as well as the inverse proportionality of prefrontal cortex activity to power in the alpha band of EEG. To search for a specific EEG band where the asymmetric activation in the prefrontal cortex by sound-induced affects is mainly reflected, we measured 32 college students' EEGs; 11 bands ranged from 6.5 to 35.0 Hz, at Fp1 and Fp2 sites. The power in the alpha band (8.0 to 13.0 Hz) at Fp2, especially in the alpha-2 band (9.0 to 11.0 Hz) increased while the students listened to music, during which participants reported positive affect. In contrast, the power at Fp1 increased while the students listened to noise, during which participants reported negative affect. These results imply that sound-induced positive affect increases relative left-sided activation in the prefrontal cortex, whereas induced negative affect elicits the opposite pattern of asymmetric activation.

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

    Science.gov (United States)

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

    2016-11-01

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

  16. Larger mid-dorsolateral prefrontal gray matter volume in young binge drinkers revealed by voxel-based morphometry.

    Directory of Open Access Journals (Sweden)

    Sonia Doallo

    Full Text Available Binge drinking or heavy episodic drinking is a high prevalent pattern of alcohol consumption among young people in several countries. Despite increasing evidence that binge drinking is associated with impairments in executive aspects of working memory (i.e. self-ordered working memory, processes known to depend on the mid-dorsolateral prefrontal cortex (Brodmann areas 46 and 9, less is known about the impact of binge drinking on prefrontal gray matter integrity. Here, we investigated the effects of binge drinking on gray matter volume of mid- dorsolateral prefrontal cortex in youths. We used voxel-based morphometry on the structural magnetic resonance images of subjects reporting a persistent (at least three years binge drinking pattern of alcohol use (n = 11; age 22.43 ± 1.03 and control subjects (n = 21; age 22.18 ± 1.08 to measure differences in gray matter volume between both groups. In a region of interest analysis of the mid-dorsolateral prefrontal cortex, after co-varying for age and gender, we observed significantly larger gray matter volume in the left mid-dorsolateral prefrontal cortex (Brodmann areas 46 and 9 in binge drinkers in comparison with control subjects. Furthermore, there was a significant positive correlation between left mid-dorsolateral prefrontal cortex volume and Self-Ordered Pointing Test (SOPT total errors score in binge drinkers. The left mid-dorsolateral prefrontal cortex volume also correlated with the quantity and speed of alcohol intake. These findings indicate that a repeated exposure to alcohol -that does not meet criteria for alcohol dependence- throughout post-adolescent years and young adulthood is linked with structural anomalies in mid-dorsolateral prefrontal regions critically involved in executive aspects of working memory.

  17. Prefrontal activation deficits during episodic memory in schizophrenia.

    Science.gov (United States)

    Ragland, John D; Laird, Angela R; Ranganath, Charan; Blumenfeld, Robert S; Gonzales, Sabina M; Glahn, David C

    2009-08-01

    Episodic memory impairments represent a core deficit in schizophrenia that severely limits patients' functional outcome. This quantitative meta-analysis of functional imaging studies of episodic encoding and retrieval tests the prediction that these deficits are most consistently associated with dysfunction in the prefrontal cortex. Activation likelihood estimation (ALE) was used to perform a quantitative meta-analysis of functional imaging studies that contrasted patients with schizophrenia and healthy volunteers during episodic encoding and retrieval. From a pool of 36 potential studies, 18 whole-brain studies in standard space that included a healthy comparison sample and low-level baseline contrast were selected. As predicted, patients showed less prefrontal activation than comparison subjects in the frontal pole, dorsolateral and ventrolateral prefrontal cortex during encoding, and the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during retrieval. The ventrolateral prefrontal cortex encoding deficits were not present in studies that provided patients with encoding strategies, but dorsolateral prefrontal cortex deficits remained and were not secondary to group performance differences. The only medial temporal lobe finding was relatively greater patient versus comparison subject activation in the parahippocampal gyrus during encoding and retrieval. The finding of prominent prefrontal dysfunction suggests that cognitive control deficits strongly contribute to episodic memory impairment in schizophrenia. Memory rehabilitation approaches developed for patients with frontal lobe lesions and pharmacotherapy approaches designed to improve prefrontal cortex function may therefore hold special promise for remediating memory deficits in patients with schizophrenia.

  18. Plasticity in the prefrontal cortex of adult rats

    Science.gov (United States)

    Kolb, Bryan; Gibb, Robbin

    2015-01-01

    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. PMID:25691857

  19. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

    Kostopoulos, Penelope; Petrides, Michael

    2016-01-01

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

  2. Dopamine Development in the Mouse Orbital Prefrontal Cortex Is Protracted and Sensitive to Amphetamine in Adolescence.

    Science.gov (United States)

    Hoops, Daniel; Reynolds, Lauren M; Restrepo-Lozano, Jose-Maria; Flores, Cecilia

    2018-01-01

    The prefrontal cortex (PFC) is divided into subregions, including the medial and orbital prefrontal cortices. Dopamine connectivity in the medial PFC (mPFC) continues to be established throughout adolescence as the result of the continuous growth of axons that innervated the nucleus accumbens (NAcc) prior to adolescence. During this period, dopamine axons remain vulnerable to environmental influences, such as drugs used recreationally by humans. The developmental trajectory of the orbital prefrontal dopamine innervation remains almost completely unstudied. Nonetheless, the orbital PFC (oPFC) is critical for some of the most complex functions of the PFC and is disrupted by drugs of abuse, both in adolescent humans and rodents. Here, we use quantitative neuroanatomy, axon-initiated viral-vector recombination, and pharmacology in mice to determine the spatiotemporal development of the dopamine innervation to the oPFC and its vulnerability to amphetamine in adolescence. We find that dopamine innervation to the oPFC also continues to increase during adolescence and that this increase is due to the growth of new dopamine axons to this region. Furthermore, amphetamine in adolescence dramatically reduces the number of presynaptic sites on oPFC dopamine axons. In contrast, dopamine innervation to the piriform cortex is not protracted across adolescence and is not impacted by amphetamine exposure during adolescence, indicating that dopamine development during adolescence is a uniquely prefrontal phenomenon. This renders these fibers, and the PFC in general, particularly vulnerable to environmental risk factors during adolescence, such as recreational drug use.

  3. Mentalizing ability in patients with prefrontal cortex damage.

    Science.gov (United States)

    Yeh, Zai-Ting; Lo, Chiao-Yu; Tsai, Ming-Dar; Tsai, Ming-Cheng

    2015-01-01

    Mentalizing ability is the issue in the social cognition of patients with brain injury that has received the most attention. The present study investigated mentalization ability in patients with prefrontal cortex damage. The aims of this study were to investigate: (a) whether patients with prefrontal cortex damage are impaired in mentalizing ability, including theory of mind (ToM) and empathy; (b) whether patients with ventromedial prefrontal cortex damage are impaired in different aspects of ToM; (c) whether patients with ventromedial prefrontal cortex damage are impaired in different aspects of empathy; and (d) whether impairment of mentalizing ability in patients with prefrontal cortex damage can be explained by executive dysfunction. Mini-Mental State Examination (MMSE), Matrix Reasoning subtest, working memory, executive function, theory of mind, and empathy assessments were conducted on eight patients with ventromedial prefrontal cortex damage, 15 patients with dorsolateral prefrontal cortex damage, and 19 normal comparisons matched for level of education and intelligence. The results showed that performance on affective and nonverbal theory of mind was significantly lower in patients with dorsolateral prefrontal cortex damage than in the comparison group. Performance on personal distress items of empathy was significantly lower in the ventromedial prefrontal cortex damage group than in the dorsolateral prefrontal cortex damage group. In addition, further multiple regression analysis showed that affective theory of mind could be explained by the Wisconsin Card Sorting Test-Modified (WCST-M), with an explained variance of up to 44%. The present study suggests that the impairment of mentalizing ability in patients with prefrontal cortex damage is partially the result of executive dysfunction.

  4. Prefrontal single-unit firing associated with deficient extinction in mice

    OpenAIRE

    Fitzgerald, Paul J.; Whittle, Nigel; Flynn, Shaun M; Graybeal, Carolyn; Pinard, Courtney; Gunduz-Cinar, Ozge; Kravitz, Alexxai; Singewald, Nicolas; Holmes, Andrew

    2013-01-01

    The neural circuitry mediating fear extinction has been increasingly well studied and delineated. The rodent infralimbic subregion (IL) of the ventromedial prefrontal cortex (vmPFC) has been found to promote extinction, whereas the prelimbic cortex (PL) demonstrates an opposing, pro-fear, function. Studies employing in vivo electrophysiological recordings have observed that while increased IL single-unit firing and bursting predicts robust extinction retrieval, increased PL firing can correla...

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  8. Electrophysiological mapping of novel prefrontal - cerebellar pathways.

    Science.gov (United States)

    Watson, Thomas C; Jones, Matthew W; Apps, Richard

    2009-01-01

    Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non-motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL) and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35 ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre); they were not attenuated by local anaesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency (approximately 30 ms). Single unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s) of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

  9. Electrophysiological mapping of novel prefrontal - cerebellar pathways

    Directory of Open Access Journals (Sweden)

    Thomas C Watson

    2009-08-01

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

  10. Dorsolateral Prefrontal Contributions to Human Intelligence

    Science.gov (United States)

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

    2012-01-01

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

  11. Anterior prefrontal involvement in implicit contextual change detection

    Directory of Open Access Journals (Sweden)

    Stefan Pollmann

    2009-10-01

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

  12. Hippocampal-Prefrontal Theta Oscillations Support Memory Integration.

    Science.gov (United States)

    Backus, Alexander R; Schoffelen, Jan-Mathijs; Szebényi, Szabolcs; Hanslmayr, Simon; Doeller, Christian F

    2016-02-22

    Integration of separate memories forms the basis of inferential reasoning--an essential cognitive process that enables complex behavior. Considerable evidence suggests that both hippocampus and medial prefrontal cortex (mPFC) play a crucial role in memory integration. Although previous studies indicate that theta oscillations facilitate memory processes, the electrophysiological mechanisms underlying memory integration remain elusive. To bridge this gap, we recorded magnetoencephalography data while participants performed an inference task and employed novel source reconstruction techniques to estimate oscillatory signals from the hippocampus. We found that hippocampal theta power during encoding predicts subsequent memory integration. Moreover, we observed increased theta coherence between hippocampus and mPFC. Our results suggest that integrated memory representations arise through hippocampal theta oscillations, possibly reflecting dynamic switching between encoding and retrieval states, and facilitating communication with mPFC. These findings have important implications for our understanding of memory-based decision making and knowledge acquisition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Maternal prefrontal cortex activation by newborn infant odors.

    Science.gov (United States)

    Nishitani, Shota; Kuwamoto, Saori; Takahira, Asuka; Miyamura, Tsunetake; Shinohara, Kazuyuki

    2014-03-01

    Mothers are attracted by infant cues of a variety of different modalities. To clarify the possible neural mechanisms underlying maternal attraction to infant odor cues, we used near-infrared spectroscopy to examine prefrontal cortex (PFC) activity during odor detection tasks in which 19 mothers and 19 nulliparous females (nonmothers) were presented with infant or adult male odors. They were instructed to make a judgment about whether they smelled an odor during each task. We estimated the PFC activity by measuring the relative oxyhemoglobin (oxyHb) concentrations. The results showed that while detecting the infant odors, bilateral PFC activities were increased in mothers but not in nonmothers. In contrast, adult male odors activated the PFC similarly in mothers and nonmothers. These findings suggest that maternal activation of the PFC in response to infant odors explains a part of the neural mechanisms for maternal attraction to infant odors.

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

    Science.gov (United States)

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

    2006-06-01

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

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

    Science.gov (United States)

    Watson, Thomas C; Becker, Nadine; Apps, Richard; Jones, Matthew W

    2014-01-01

    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-anesthetized 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. 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.

  17. Acetazolamide potentiates the afferent drive to prefrontal cortex in vivo.

    Science.gov (United States)

    Bueno-Junior, Lezio S; Ruggiero, Rafael N; Rossignoli, Matheus T; Del Bel, Elaine A; Leite, Joao P; Uchitel, Osvaldo D

    2017-01-01

    The knowledge on real-time neurophysiological effects of acetazolamide is still far behind the wide clinical use of this drug. Acetazolamide - a carbonic anhydrase inhibitor - has been shown to affect the neuromuscular transmission, implying a pH-mediated influence on the central synaptic transmission. To start filling such a gap, we chose a central substrate: hippocampal-prefrontal cortical projections; and a synaptic phenomenon: paired-pulse facilitation (a form of synaptic plasticity) to probe this drug's effects on interareal brain communication in chronically implanted rats. We observed that systemic acetazolamide potentiates the hippocampal-prefrontal paired-pulse facilitation. In addition to this field electrophysiology data, we found that acetazolamide exerts a net inhibitory effect on prefrontal cortical single-unit firing. We propose that systemic acetazolamide reduces the basal neuronal activity of the prefrontal cortex, whereas increasing the afferent drive it receives from the hippocampus. In addition to being relevant to the clinical and side effects of acetazolamide, these results suggest that exogenous pH regulation can have diverse impacts on afferent signaling across the neocortex. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  18. Discourse Production Following Injury to the Dorsolateral Prefrontal Cortex

    Science.gov (United States)

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

    2012-01-01

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

  19. Prefrontal Cortex: A Mystery of Belated Memories.

    Science.gov (United States)

    Eichenbaum, Howard

    2017-06-05

    A recent study suggests that the prefrontal cortex gradually becomes critical as a storage site for remotely acquired memories. How do we interpret this observation in light of the well-known functional role of the prefrontal cortex in cognition and memory? Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Neuropeptide S receptor gene: fear-specific modulations of prefrontal activation.

    Science.gov (United States)

    Tupak, Sara V; Reif, Andreas; Pauli, Paul; Dresler, Thomas; Herrmann, Martin J; Domschke, Katharina; Jochum, Clara; Haas, Elisabeth; Baumann, Christian; Weber, Heike; Fallgatter, Andreas J; Deckert, Jürgen; Ehlis, Ann-Christine

    2013-02-01

    Since central administration of neuropeptide S (NPS) has been shown to exert anxiolytic effects on rodent behavior in a number of studies, genetic variants of its cognate G-protein coupled receptor (NPSR1) became the focus of several recent human studies on anxiety and anxiety disorders. The T allele of rs324981, which goes along with enhanced receptor function, was associated with panic disorder, increased anxiety sensitivity in healthy subjects, attenuated prefrontal brain activation and elevated amygdala responses to fear-relevant stimuli. To investigate whether prefrontal attenuations in rs324981 T allele carriers are specific to fear-relevant stimulus content and cannot be attributed to a generally higher interference of emotional stimuli, 92 subjects performed a combined cognitive and emotional Stroop task while oxygenation changes in the prefrontal cortex were recorded using functional near-infrared spectroscopy. Results showed a specific NPSR1 gene activation modulation in response to fear-relevant word stimuli. Only A-homozygotes displayed an emotional Stroop effect in terms of increased activation to fear-relevant stimuli in medial and dorsolateral prefrontal cortex. Specifically, activation in the fear-relevant condition was higher in A-homozygotes as compared to T allele carriers while no group differences were found during neutral, congruent or highly interfering incongruent color word presentation. The current results are in line with earlier imaging genetic studies and suggest a potential protective function of the NPSR1 rs324981 A/A genotype against pathologically enhanced anxiety that might be explained by stronger reflective prefrontal regulation over the subcortical fear response. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. 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

  2. Lucid dreaming and ventromedial versus dorsolateral prefrontal task performance.

    Science.gov (United States)

    Neider, Michelle; Pace-Schott, Edward F; Forselius, Erica; Pittman, Brian; Morgan, Peter T

    2011-06-01

    Activity in the prefrontal cortex may distinguish the meta-awareness experienced during lucid dreams from its absence in normal dreams. To examine a possible relationship between dream lucidity and prefrontal task performance, we carried out a prospective study in 28 high school students. Participants performed the Wisconsin Card Sort and Iowa Gambling tasks, then for 1 week kept dream journals and reported sleep quality and lucidity-related dream characteristics. Participants who exhibited a greater degree of lucidity performed significantly better on the task that engages the ventromedial prefrontal cortex (the Iowa Gambling Task), but degree of lucidity achieved did not distinguish performance on the task that engages the dorsolateral prefrontal cortex (the Wisconsin Card Sort Task), nor did it distinguish self-reported sleep quality or baseline characteristics. The association between performance on the Iowa Gambling Task and lucidity suggests a connection between lucid dreaming and ventromedial prefrontal function. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Age-related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence

    OpenAIRE

    Wiggins, Jillian Lee; Bedoyan, Jirair K.; Carrasco, Melisa; Swartz, Johnna R.; Martin, Donna M.; Monk, Christopher S.

    2012-01-01

    The S and LG alleles of the serotonin transporter-linked polymorphic region (5-HTTLPR) lower serotonin transporter expression. These low expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala-prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces de...

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

    Science.gov (United States)

    Romanski, L M; Diehl, M M

    2011-08-25

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

  5. 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.

  6. Prefrontal activity links nonoverlapping events in memory.

    Science.gov (United States)

    Gilmartin, Marieke R; Miyawaki, Hiroyuki; Helmstetter, Fred J; Diba, Kamran

    2013-06-26

    The medial prefrontal cortex (mPFC) plays an important role in memory. By maintaining a working memory buffer, neurons in prelimbic (PL) mPFC may selectively contribute to learning associations between stimuli that are separated in time, as in trace fear conditioning (TFC). Until now, evidence for this bridging role was largely descriptive. Here we used optogenetics to silence neurons in the PL mPFC of rats during learning in TFC. Memory formation was prevented when mPFC was silenced specifically during the interval separating the cue and shock. Our results provide support for a working memory function for these cells and indicate that associating two noncontiguous stimuli requires bridging activity in PL mPFC.

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

    Directory of Open Access Journals (Sweden)

    Scot eMcIntosh

    2013-08-01

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

  8. Is the prefrontal cortex necessary for establishing cognitive sets?

    DEFF Research Database (Denmark)

    Rowe, James B; Sakai, Katsuyuki; Lund, Torben E

    2007-01-01

    There is evidence from neuroimaging that the prefrontal cortex may be involved in establishing task set activity in advance of presentation of the task itself. To find out whether it plays an essential role, we examined patients with unilateral lesions of the rostral prefrontal cortex. They were...... regions, as evidenced by reduced correlations between them during instruction delays. The results suggest that the left rostral prefrontal cortex is indeed required for establishing a cognitive set but that the essential function is to support the functional connectivity among the task-related regions....

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

    Science.gov (United States)

    Brincat, Scott L; Miller, Earl K

    2016-09-14

    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. 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. Copyright © 2016 the authors 0270-6474/16/369739-16$15.00/0.

  10. Relationship of Cannabinoid CB1 Receptor and Cholecystokinin Immunoreactivity in Monkey Dorsolateral Prefrontal Cortex

    OpenAIRE

    Eggan, Stephen M.; Melchitzky, Darlene S.; Sesack, Susan R.; Fish, Kenneth N.; Lewis, David A.

    2010-01-01

    Exposure to cannabis impairs cognitive functions reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC) and increases the risk of schizophrenia. The actions of cannabis are mediated via the brain cannabinoid 1 receptor (CB1R), which in rodents is heavily localized to the axon terminals of cortical GABA basket neurons that contain cholecystokinin (CCK). Differences in the laminar distribution of CB1R-immunoreactive (IR) axons have been reported between rodent and monkey neocort...

  11. Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning

    OpenAIRE

    Parvin Babaei; Bahram Soltani Tehrani; Arsalan Alizadeh; Morteza Nakhostin

    2011-01-01

    "nThe purpose of the present study was to determine the role of medial prefrontal cortex (mPFC) dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH) and antagonist, clozapine (CLZ) into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then e...

  12. Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa.

    Science.gov (United States)

    Favaro, Angela; Clementi, Maurizio; Manara, Renzo; Bosello, Romina; Forzan, Monica; Bruson, Alice; Tenconi, Elena; Degortes, Daniela; Titton, Francesca; Di Salle, Francesco; Santonastaso, Paolo

    2013-07-01

    Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess nega tively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa. All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging. We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing. Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels. Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.

  13. Optogenetic dissection of medial prefrontal cortex circuitry

    Directory of Open Access Journals (Sweden)

    Danai eRiga

    2014-12-01

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

  14. Prefrontal Dopamine in Associative Learning and Memory

    Science.gov (United States)

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

    2014-01-01

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

  15. Improved multitasking following prefrontal tDCS.

    Science.gov (United States)

    Filmer, Hannah L; Mattingley, Jason B; Dux, Paul E

    2013-01-01

    We have a limited capacity for mapping sensory information onto motor responses. This processing bottleneck is thought to be a key factor in determining our ability to make two decisions simultaneously - i.e., to multitask (Pashler, 1984, 1994; Welford, 1952). Previous functional imaging research (Dux, Ivanoff, Asplund, & Marois, 2006; Dux et al., 2009) has localised this bottleneck to the posterior lateral prefrontal cortex (pLPFC) of the left hemisphere. Currently, however, it is unknown whether this region is causally involved in multitasking performance. We investigated the role of the left pLPFC in multitasking using transcranial direct current stimulation (tDCS). The behavioural paradigm included single- and dual-task trials, each requiring a speeded discrimination of visual stimuli alone, auditory stimuli alone, or both visual and auditory stimuli. Reaction times for single- and dual-task trials were compared before, immediately after, and 20 min after anodal stimulation (excitatory), cathodal stimulation (inhibitory), or sham stimulation. The cost of responding to the two tasks (i.e., the reduction in performance for dual- vs single-task trials) was significantly reduced by cathodal stimulation, but not by anodal or sham stimulation. Overall, the results provide direct evidence that the left pLPFC is a key neural locus of the central bottleneck that limits an individual's ability to make two simple decisions simultaneously. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Prenatal restraint stress: an in vivo microdialysis study on catecholamine release in the rat prefrontal cortex.

    Science.gov (United States)

    Carboni, E; Barros, V G; Ibba, M; Silvagni, A; Mura, C; Antonelli, M C

    2010-06-16

    There is substantial evidence that prenatal exposure to adverse environmental conditions might lead to the psychiatric disorders that can appear in adolescence or in adulthood; vulnerability to drug addiction may increase as well. It is currently accepted that the alteration of catecholamine transmission in the prefrontal cortex plays a prominent role in the etiology of psychiatric disorders. We assessed basal and stimulated dopamine and noradrenaline extracellular concentration in the medial prefrontal cortex by means of microdialysis in awake male adolescent and young adult offspring of rats exposed to restraint stress in the last week of pregnancy. Catecholamine stimulation was obtained by amphetamine or nicotine. We observed that prenatal stress (PNS) did not change dopamine but decreased noradrenaline basal output in both adolescents and adults. Moreover, it decreased amphetamine stimulated dopamine output and increased amphetamine stimulated noradrenaline output. PNS decreased nicotine stimulated noradrenaline (but not dopamine output) in adults, though not in adolescents. These data show that PNS stress modifies prefrontal cortex catecholamine transmission in a complex and age dependent manner. Our results support the view that prenatal stress may be a contributing factor for the development of psychiatric disorders and that its effect may augment drug addiction vulnerability. 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Development of prospective memory: tasks based on the prefrontal-lobe model.

    Science.gov (United States)

    Ward, Heather; Shum, David; McKinlay, Lynne; Baker-Tweney, Simone; Wallace, Geoff

    2005-12-01

    This study investigated the development of prospective memory using tasks based on the prefrontal-lobe model. Three groups each of 30 children, adolescents, and young adults were compared on prospective-memory performance using ongoing tasks with two levels of cognitive demand (low and high), and two levels of importance (unstressed and stressed) of remembering prospective cues. The Self-Ordered Pointing Task (SOPT), Stroop Color Word Interference Test, and Tower of London were also used to assess relationships between prospective memory and prefrontal-lobe functions. The children remembered fewer prospective cues than either the adolescents or adults, but the adolescents and adults remembered equally well. This trend increased significantly as the cognitive demand of the ongoing tasks increased. However, stressing or not stressing the importance of remembering made no difference to prospective-memory performance. Performance on the SOPT and Stroop Colour Word Interference predicted performance on the high- but not on the low-demand condition. These findings implicate the maturation of the brain's prefrontal region in the development of prospective memory.

  18. Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

    Directory of Open Access Journals (Sweden)

    Cui Guang-bin

    2012-02-01

    Full Text Available Abstract Background Interleukin-8 (IL-8 is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC, is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. Findings In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC, and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. Conclusions Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

  19. Harmine and Imipramine Promote Antioxidant Activities in Prefrontal Cortex and Hippocampus

    Directory of Open Access Journals (Sweden)

    Gislaine Z. Réus

    2010-01-01

    Full Text Available A growing body of evidence has suggested that reactive oxygen species (ROS may play an important role in the physiopathology of depression. Evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg and imipramine (10, 20 and 30 mg/kg or saline in lipid and protein oxidation levels and superoxide dismutase (SOD and catalase (CAT activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and β-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation.

  20. Dissociable effects of prefrontal and anterior temporal cortical lesions on stereotypical gender attitudes.

    Science.gov (United States)

    Gozzi, Marta; Raymont, Vanessa; Solomon, Jeffrey; Koenigs, Michael; Grafman, Jordan

    2009-08-01

    Clinical observations of patients with ventral frontal and anterior temporal cortical lesions reveal marked abnormalities in social attitudes. A previous study in seven patients with ventral prefrontal lesions provided the first direct experimental evidence for abnormalities in social attitudes using a well-established measure of gender stereotypes, the Implicit Association Test (IAT). Here, we were able to test whether these first findings could be reproduced in a larger sample of 154 patients with penetrating head injuries, and to determine the differential effects of ventromedial prefrontal (vmPFC) and ventrolateral prefrontal (vlPFC) cortical lesions on IAT performance. In addition, we investigated the role of the superior anterior temporal lobe (aTL), recently shown to represent conceptual social knowledge. First, we used a linear regression model to identify the role of each of the three regions, while controlling for the extent of damage to other regions. We found that larger lesions in either the vmPFC or the superior aTL were associated with increased stereotypical attitudes, whereas larger lesions in the vlPFC were associated with decreased stereotypical attitudes. Second, in a confirmatory analysis, we grouped patients by lesion location and compared their performance on the IAT with that of healthy volunteers. Compared to controls, patients with lesions in either the vmPFC or the superior aTL showed increased stereotypical attitudes, whereas patients with lesions in the vlPFC showed decreased stereotypical attitudes. The functional contributions of these regions in social attitudes are discussed.

  1. Treadmill exercise induces age and protocol-dependent epigenetic changes in prefrontal cortex of Wistar rats.

    Science.gov (United States)

    Cechinel, Laura Reck; Basso, Carla Giovana; Bertoldi, Karine; Schallenberger, Bruna; de Meireles, Louisiana Carolina Ferreira; Siqueira, Ionara Rodrigues

    2016-10-15

    Some studies have linked age-related beneficial effects of exercise and epigenetic mechanisms. Although, the impact of treadmill exercise on histone acetylation, histone and DNA methylation marks in aged cortices yet remains poorly understood. Considering the role of frontal cortex on brain functions, we investigated the potential of different exercise protocols, single session and daily exercise, to modulate epigenetic marks, namely global H4 acetylation, histone methyltransferase activity (HMT H3K27) and levels of DNA methytransferase (DNMT1 and DNMT3b) in prefrontal cortices from 3 and 21-months aged Wistar rats. The animals were submitted to two treadmill exercise protocols, single session (20min) or daily moderate (20min/day during 14days). The daily exercise protocol induced an increased in histone H4 acetylation levels in prefrontal cortices of 21-months-old rats, without any effects in young adult group. DNMT3b levels were increased in aged cortices of animals submitted to single session of exercise. These results indicate that prefrontal cortex is susceptible to epigenetic changes in a protocol dependent-manner and that H4 acetylation levels and DNMT3b content changes might be linked at least in part to exercise-induced effects on brain functions. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Qu, Yang; Galvan, Adriana; Fuligni, Andrew J; Lieberman, Matthew D; Telzer, Eva H

    2015-08-12

    Adolescence is a critical developmental phase during which risk-taking behaviors increase across a variety of species, raising the importance of understanding how brain changes contribute to such behaviors. While the prefrontal cortex is thought to influence adolescent risk taking, the specific ways in which it functions are unclear. Using longitudinal functional magnetic resonance imaging in human adolescents, we found that ventrolateral prefrontal cortex (VLPFC) activation decreased during an experimental risk-taking task over time, with greater declines in VLPFC associated with greater declines in self-reported risky behavior. Furthermore, greater decreases in functional coupling between the medial prefrontal cortex (MPFC) and ventral striatum over time were associated with decreases in self-reported risky behavior. Thus, disparate roles of the VLPFC and MPFC modulate longitudinal declines in adolescent risk taking. Adolescence is a developmental period marked by steep increases in risk-taking behavior coupled with dramatic brain changes. Although theories propose that the prefrontal cortex (PFC) may influence adolescent risk taking, the specific ways in which it functions remain unclear. We report the first longitudinal functional magnetic resonance imaging study to examine how neural activation during risk taking changes over time and contributes to adolescents' real-life risk-taking behavior. We find that longitudinal declines in activation of the ventrolateral PFC are linked to declines in adolescent risk taking, whereas the medial PFC influences adolescent risk taking via its functional neural coupling with reward-related regions. This is the first study to identify the mechanism by which different regions of the PFC disparately contribute to declines in risk taking. Copyright © 2015 the authors 0270-6474/15/3511308-07$15.00/0.

  3. Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

    Science.gov (United States)

    Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

    2015-03-04

    The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs. Copyright © 2015 the authors 0270-6474/15/354104-08$15.00/0.

  4. Temporal Dynamics of Acute Stress-Induced Dendritic Remodeling in Medial Prefrontal Cortex and the Protective Effect of Desipramine

    DEFF Research Database (Denmark)

    Nava, Nicoletta; Treccani, Giulia; Alabsi, Abdelrahman

    2017-01-01

    Stressful events are associated with increased risk of mood disorders. Volumetric reductions have been reported in brain areas critical for the stress response, such as medial prefrontal cortex (mPFC), and dendritic remodeling has been proposed as an underlying factor. Here, we investigated...

  5. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Rizavi, Hooriyah S; Ren, Xinguo; Fareed, Jawed; Hoppensteadt, Debra A; Roberts, Rosalinda C; Conley, Robert R; Dwivedi, Yogesh

    2012-01-01

    Teenage suicide is a major public health concern, but its neurobiology is not well understood. Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression-two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims. We therefore measured the gene and protein expression levels of proinflammatory cytokines interleukin (IL)-1β, IL-6, and tissue necrosis factor (TNF)-α in the prefrontal cortex (PFC) of 24 teenage suicide victims and 24 matched normal control subjects. Our results show that the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α were significantly increased in Brodmann area 10 (BA-10) of suicide victims compared with normal control subjects. These results suggest an important role for IL-1β, IL-6, and TNF-α in the pathophysiology of suicidal behavior and that proinflammatory cytokines may be an appropriate target for developing therapeutic agents. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Prefrontal contributions to relational encoding in amnestic mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Chris M. Foster

    2016-01-01

    Full Text Available Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI. Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads, both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease.

  8. Comparison of the adolescent and adult mouse prefrontal cortex proteome

    Science.gov (United States)

    Small, Amanda T.; Spanos, Marina; Burrus, Brainard M.

    2017-01-01

    Adolescence is a developmental period characterized by unique behavioral phenotypes (increased novelty seeking, risk taking, sociability and impulsivity) and increased risk for destructive behaviors, impaired decision making and psychiatric illness. Adaptive and maladaptive adolescent traits have been associated with development of the medial prefrontal cortex (mPFC), a brain region that mediates regulatory control of behavior. However, the molecular changes that underlie brain development and behavioral vulnerability have not been fully characterized. Using high-throughput 2D DIGE spot profiling with identification by MALDI-TOF mass spectrometry, we identified 62 spots in the PFC that exhibited age-dependent differences in expression. Identified proteins were associated with diverse cellular functions, including intracellular signaling, synaptic plasticity, cellular organization and metabolism. Separate Western blot analyses confirmed age-related changes in DPYSL2, DNM1, STXBP1 and CFL1 in the mPFC and expanded these findings to the dorsal striatum, nucleus accumbens, motor cortex, amygdala and ventral tegmental area. Ingenuity Pathway Analysis (IPA) identified functional interaction networks enriched with proteins identified in the proteomics screen, linking age-related alterations in protein expression to cellular assembly and development, cell signaling and behavior, and psychiatric illness. These results provide insight into potential molecular components of adolescent cortical development, implicating structural processes that begin during embryonic development as well as plastic adaptations in signaling that may work in concert to bring the cortex, and other brain regions, into maturity. PMID:28570644

  9. Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder.

    Science.gov (United States)

    Pu, Shenghong; Nakagome, Kazuyuki; Yamada, Takeshi; Yokoyama, Katsutoshi; Matsumura, Hiroshi; Yamada, Sayaka; Sugie, Takuya; Miura, Akihiko; Mitani, Hideaki; Iwata, Masaaki; Nagata, Izumi; Kaneko, Koichi

    2015-08-01

    Despite the known relationship between prefrontal function and increased suicidality during major depressive episodes, the links between prefrontal function and suicidality remain unclear in major depressive disorder (MDD). Suicidal ideation usually precedes a suicide attempt. If prefrontal cortex (PFC) activity is a biomarker for suicidal ideation in depression, monitoring it could be useful for suicide prevention. Therefore, in this study, we assessed the association between prefrontal function and suicidal ideation in MDD. Prefrontal function in 67 patients with MDD (31 with suicidal ideation and 36 without) and 67 age-, gender-, and intelligence quotient-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). Regional hemodynamic changes were significantly smaller in patients with MDD than in HCs in prefrontal and temporal regions. Hemodynamic changes in the right dorsolateral PFC (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in patients with MDD with suicidal ideation were significantly smaller than in those without suicidal ideation. In addition, hemodynamic changes correlated negatively with the severity of suicidal ideation in the DLPFC, OFC, and FPC in patients with MDD. Further studies with a larger sample size are required to verify our findings. These results suggest that the DLPFC, OFC, and FPC are brain substrates of suicidal ideation in depressive states in patients with MDD, and that NIRS data can be employed as a clinically useful biomarker for the assessment of suicide risk. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Alcohol dependence associated with increased utilitarian moral judgment: a case control study

    National Research Council Canada - National Science Library

    Khemiri, Lotfi; Guterstam, Joar; Franck, Johan; Jayaram-Lindström, Nitya

    2012-01-01

    .... Patients with alcohol dependence (AD) also exhibit impairments in functions mediated by the prefrontal cortex, but whether they exhibit increased utilitarian moral reasoning has not previously been investigated...

  11. Changes in prefrontal cortical behaviour depend upon familiarity on a bimanual co-ordination task: an fNIRS study.

    Science.gov (United States)

    Leff, Daniel Richard; Elwell, Clare E; Orihuela-Espina, Felipe; Atallah, Louis; Delpy, David T; Darzi, Ara W; Yang, Guang Zhong

    2008-01-15

    To investigate neurocognitive mechanisms associated with task-related expertise development, this paper investigates serial changes in prefrontal activation patterns using functional near infrared spectroscopy (fNIRS). We evaluate cortical function in 62 healthy subjects with varying experience during serial evaluations of a knot-tying task. All tasks were performed bimanually and self paced, with fixed episodes of motor rest for five repetitions. Improvements in technical skill were evaluated using dexterity indices to quantify time, total movements and pathlength required to complete trials. Significant improvements in technical skills were observed in novices between the 2nd and 3rd trials, associated with increasing task familiarity. In trained subjects, minimal fluctuation in task-related oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) changes were observed in association with more stable task performance. In contrast, two significant transitions in prefrontal haemodynamic change were observed in novices. Greater task-related increases in HbO(2) and decreases in HHb were identified on the second trial compared to the first. Relative decreases in HbO(2) and increases in HHb change were observed between the third and fourth, and fourth and fifth trials respectively. These data suggest that prefrontal processing across five knot-tying trials is influenced by the level of experience on a task. Modifications in prefrontal activation appear to confer technical performance adaptation in novices.

  12. The role of catecholamine innervation in the medial prefrontal cortex on the regulation of body weight and food intake.

    Science.gov (United States)

    Gálosi, Rita; Hajnal, Andras; Petykó, Zoltán; Hartmann, Géza; Karádi, Zoltán; Lénárd, László

    2015-06-01

    Effects of 6-hydroxydopamine (6-OHDA) lesions in the medial prefrontal cortex with or without protection of norepinephrine (NE) fibers were examined on basic regulatory processes of feeding. Daily body weight, food and water intake were measured. Locomotor activity, ingestion after food or water deprivation, and preference for 5% and 10% glucose solution were examined. Dopamine (DA) and NE content, as well as, tyrosine hydroxylase immunoreactivity were assessed to confirm the neurotoxic effect of treatments. 6-OHDA lesions of the medial prefrontal cortex with or without NE fiber protection resulted in body weight loss. Diminished habituation in open field tests, i.e. a persistently high motor activity, was also observed. Application of 6-OHDA with NE fiber protection led to increased food consumption following food-deprivation and to enhanced glucose preference. Enhanced intake of 10% over 5% glucose solution was also detected. 6-OHDA lesion resulted in a decrease to 20% of NE tissue concentration and only to 75% of DA concentration. In case of lesion with NE protection the NE content decreased to 69% and DA level to 51% with significant loss of tyrosine hydroxylase positive fibers in the deeper layers of the medial prefrontal cortex. DA depletion in the medial prefrontal cortex resulted in increased behavioral responsiveness to hunger and glucose, as well as, to open field environment. Pronounced lesion of NE terminals caused increased reaction to the environment in open field but not to hunger or glucose solution. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Characterization of Spontaneous, Transient Adenosine Release in the Caudate-Putamen and Prefrontal Cortex

    Science.gov (United States)

    Nguyen, Michael D.; Lee, Scott T.; Ross, Ashley E.; Ryals, Matthew; Choudhry, Vishesh I.; Venton, B. Jill

    2014-01-01

    Adenosine is a neuroprotective agent that inhibits neuronal activity and modulates neurotransmission. Previous research has shown adenosine gradually accumulates during pathologies such as stroke and regulates neurotransmission on the minute-to-hour time scale. Our lab developed a method using carbon-fiber microelectrodes to directly measure adenosine changes on a sub-second time scale with fast-scan cyclic voltammetry (FSCV). Recently, adenosine release lasting a couple of seconds has been found in murine spinal cord slices. In this study, we characterized spontaneous, transient adenosine release in vivo, in the caudate-putamen and prefrontal cortex of anesthetized rats. The average concentration of adenosine release was 0.17±0.01 µM in the caudate and 0.19±0.01 µM in the prefrontal cortex, although the range was large, from 0.04 to 3.2 µM. The average duration of spontaneous adenosine release was 2.9±0.1 seconds and 2.8±0.1 seconds in the caudate and prefrontal cortex, respectively. The concentration and number of transients detected do not change over a four hour period, suggesting spontaneous events are not caused by electrode implantation. The frequency of adenosine transients was higher in the prefrontal cortex than the caudate-putamen and was modulated by A1 receptors. The A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine, 6 mg/kg i.p.) increased the frequency of spontaneous adenosine release, while the A1 agonist CPA (N6-cyclopentyladenosine, 1 mg/kg i.p.) decreased the frequency. These findings are a paradigm shift for understanding the time course of adenosine signaling, demonstrating that there is a rapid mode of adenosine signaling that could cause transient, local neuromodulation. PMID:24494035

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Abnormalities of Dorsolateral Prefrontal Function in Women With Premenstrual Dysphoric Disorder: A Multimodal Neuroimaging Study

    Science.gov (United States)

    Baller, Erica B.; Wei, Shau-Ming; Kohn, Philip D.; Rubinow, David R.; Alarcón, Gabriela; Schmidt, Peter J.; Berman, Karen F.

    2014-01-01

    Objective To investigate the neural substrate of premenstrual dysphoric disorder (PMDD), the authors used [15O]H2O positron emission tomography (PET) regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal measurements during working memory in conjunction with a 6-month hormone manipulation protocol. Method PET and fMRI scans were obtained from women with prospectively confirmed PMDD and asymptomatic comparison subjects while they completed the n-back task during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate, leuprolide plus estradiol, and leuprolide plus progesterone. Fifteen patients and 15 matched comparison subjects underwent PET imaging. Fourteen patients and 14 comparison subjects underwent fMRI. For each hormone condition, rCBF was measured with [15O]H2O PET, and BOLD signal was measured with fMRI, both during an n-back working memory paradigm. Global Assessment of Functioning Scale (GAF) scores and clinical characteristics were obtained for each patient before hormone manipulation, and symptoms were measured before and during the protocol. Results In both the PET and fMRI studies, a main effect of diagnosis was observed, with PMDD patients showing greater prefrontal activation than comparison subjects. In the patient group, the degree to which dorsolateral prefrontal cortex activation was abnormally increased correlated with several dimensions of disease: disability as indicated by GAF scores, age at symptom onset, duration of PMDD, and differences in pre- and postmenses PMDD symptoms. Conclusions Abnormal working memory activation in PMDD, specifically in the dorsolateral prefrontal cortex, is related to PMDD severity, symptoms, age at onset, and disease burden. These results support the clinical relevance of the findings and the proposal that dorsolateral prefrontal cortex dysfunction represents a substrate of risk for PMDD. The

  16. Effects of prefrontal cortex damage on emotion understanding: EEG and behavioural evidence.

    Science.gov (United States)

    Perry, Anat; Saunders, Samantha N; Stiso, Jennifer; Dewar, Callum; Lubell, Jamie; Meling, Torstein R; Solbakk, Anne-Kristin; Endestad, Tor; Knight, Robert T

    2017-04-01

    Humans are highly social beings that interact with each other on a daily basis. In these complex interactions, we get along by being able to identify others' actions and infer their intentions, thoughts and feelings. One of the major theories accounting for this critical ability assumes that the understanding of social signals is based on a primordial tendency to simulate observed actions by activating a mirror neuron system. If mirror neuron regions are important for action and emotion recognition, damage to regions in this network should lead to deficits in these domains. In the current behavioural and EEG study, we focused on the lateral prefrontal cortex including dorsal and ventral prefrontal cortex and utilized a series of task paradigms, each measuring a different aspect of recognizing others' actions or emotions from body cues. We examined 17 patients with lesions including (n = 8) or not including (n = 9) the inferior frontal gyrus, a core mirror neuron system region, and compared their performance to matched healthy control subjects (n = 18), in behavioural tasks and in an EEG observation-execution task measuring mu suppression. Our results provide support for the role of the lateral prefrontal cortex in understanding others' emotions, by showing that even unilateral lesions result in deficits in both accuracy and reaction time in tasks involving the recognition of others' emotions. In tasks involving the recognition of actions, patients showed a general increase in reaction time, but not a reduction in accuracy. Deficits in emotion recognition can be seen by either direct damage to the inferior frontal gyrus, or via damage to dorsal lateral prefrontal cortex regions, resulting in deteriorated performance and less EEG mu suppression over sensorimotor cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Auditory inhibitory gating in medial prefrontal cortex: Single unit and local field potential analysis.

    Science.gov (United States)

    Mears, R P; Klein, A C; Cromwell, H C

    2006-08-11

    Medial prefrontal cortex is a crucial region involved in inhibitory processes. Damage to the medial prefrontal cortex can lead to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The goal of the present study was to examine the basic properties of inhibitory gating in this brain region in rats. Inhibitory gating has recently been proposed as a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to the findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i.e. schizophrenia). We used the standard inhibitory gating two-tone paradigm with a 500 ms interval between tones and a 10 s interval between tone pairs. We recorded both single unit and local field potentials from chronic microwire arrays implanted in the medial prefrontal cortex. We investigated short-term (within session) and long-term (between session) variability of auditory gating and additionally examined how altering the interval between the tones influenced the potency of the inhibition. The local field potentials displayed greater variability with a reduction in the amplitudes of the tone responses over both the short and long-term time windows. The decrease across sessions was most intense for the second tone response (test tone) leading to a more robust gating (lower T/C ratio). Surprisingly, single unit responses of different varieties retained similar levels of auditory responsiveness and inhibition in both the short and long-term analysis. Neural inhibition decreased monotonically related to the increase in intertone interval. This change in gating was most consistent in the local field potentials. Subsets of single unit responses did not show the lack of inhibition even for the longer intertone intervals tested (4 s interval). These findings support the idea that the medial

  18. Positive correlation between drowsiness and prefrontal activation during a simulated speed-control driving task.

    Science.gov (United States)

    Liu, Tao

    2014-11-12

    The present study aimed to examine the relationship between drowsiness and prefrontal activation during simulated driving tasks using a wireless portable near-infrared spectroscopy device. Participants drove from start to goal along default routes with either intentional control of their driving speed (speed-control group) or not (speed-free group). Drowsiness level was assessed using a five-item Likert-type questionnaire. The behavioral data indicated longer driving time in the speed-control group than in the speed-free group, whereas no difference in the number of errors was found between the two groups. Importantly, the speed-control group showed a significant positive correlation between the drowsiness score and left prefrontal activation, whereas the speed-free group did not. The results suggest that drowsy individuals may show increased prefrontal activation as compensatory efforts to maintain the desired level of performance in tasks that require deliberate control of behaviors. Furthermore, the present study shows that near-infrared spectroscopy may provide us with a possibility to examine the state of drowsiness during daily-life operations.

  19. 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.

  20. 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.

  1. 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

  2. Reduced Prefrontal Cortical Gray Matter Volume in Young Adults Exposed to Harsh Corporal Punishment

    Science.gov (United States)

    Tomoda, Akemi; Suzuki, Hanako; Rabi, Keren; Sheu, Yi-Shin; Polcari, Ann; Teicher, Martin H.

    2010-01-01

    Objective Harsh corporal punishment (HCP) during childhood is a chronic, developmental stressor associated with depression, aggression and addictive behaviors. Exposure to traumatic stressors, such as sexual abuse, is associated with alteration in brain structure, but nothing is known about the potential neurobiological consequences of HCP. The aim of this study was to investigate whether HCP was associated with discernible alterations in gray matter volume (GMV) using voxel-based morphometry (VBM). Methods 1,455 young adults (18–25 years) were screened to identify 23 with exposure to HCP (minimum 3 years duration, 12 episodes per year, frequently involving objects) and 22 healthy controls. High-resolution T1-weighted MRI datasets were obtained using Siemens 3T trio scanner. Results GMV was reduced by 19.1% in the right medial frontal gyrus (medial prefrontal cortex; MPFC, BA10) (P = 0.037, corrected cluster level), by 14.5% in the left medial frontal gyrus (dorsolateral prefrontal cortex; DLPFC, BA 9) (P = 0.015, uncorrected cluster level) and by 16.9% in the right anterior cingulate gyrus (BA 24) (P effects on trajectories of brain development. However, it is also conceivable that differences in prefrontal cortical development may increase risk of exposure to HCP. PMID:19285558

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

    Science.gov (United States)

    Arnsten, Amy F.T.

    2009-01-01

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

  4. Selective deficit in personal moral judgment following damage to ventromedial prefrontal cortex.

    Science.gov (United States)

    Ciaramelli, Elisa; Muccioli, Michela; Làdavas, Elisabetta; di Pellegrino, Giuseppe

    2007-06-01

    Recent fMRI evidence has detected increased medial prefrontal activation during contemplation of personal moral dilemmas compared to impersonal ones, which suggests that this cortical region plays a role in personal moral judgment. However, functional imaging results cannot definitively establish that a brain area is necessary for a particular cognitive process. This requires evidence from lesion techniques, such as studies of human patients with focal brain damage. Here, we tested 7 patients with lesions in the ventromedial prefrontal cortex and 12 healthy individuals in personal moral dilemmas, impersonal moral dilemmas and non-moral dilemmas. Compared to normal controls, patients were more willing to judge personal moral violations as acceptable behaviors in personal moral dilemmas, and they did so more quickly. In contrast, their performance in impersonal and non-moral dilemmas was comparable to that of controls. These results indicate that the ventromedial prefrontal cortex is necessary to oppose personal moral violations, possibly by mediating anticipatory, self-focused, emotional reactions that may exert strong influence on moral choice and behavior.

  5. Effect of trait anxiety on prefrontal control mechanisms during emotional conflict.

    Science.gov (United States)

    Comte, Magali; Cancel, Aïda; Coull, Jennifer T; Schön, Daniele; Reynaud, Emmanuelle; Boukezzi, Sarah; Rousseau, Pierre-François; Robert, Gabriel; Khalfa, Stéphanie; Guedj, Eric; Blin, Olivier; Weinberger, Daniel R; Fakra, Eric

    2015-06-01

    Converging evidence points to a link between anxiety proneness and altered emotional functioning, including threat-related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task-related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high-order control, characterized by insufficient ACC-LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders. © 2015 Wiley Periodicals, Inc.

  6. 5-Lipoxygenase in the Prefrontal Cortex of Suicide Victims

    Science.gov (United States)

    Uz, Tolga; Dwivedi, Yogesh; Pandey, Ghanshyam N.; Roberts, Rosalinda C.; Conley, Robert R.; Manev, Radmila; Manev, Hari

    2009-01-01

    5-lipoxygenase (5-LOX), an enzyme involved in leukotriene synthesis, is expressed in the brain and has been associated with Alzheimer's disease and depression. Recently, it has been suspected that leukotriene receptor antagonists might be associated with suicide. In this work, we investigated the 5-LOX protein in the brain samples from depressed suicide victims and matching controls. We used Western immunoblotting with an antibody against Ser523-phosphorylated 5-LOX (p5-LOX) to evaluate protein kinase A-mediated 5-LOX phosphorylation, and in addition, an antibody against the total 5-LOX protein. In the total homogenate of the prefrontal cortex samples, 5-LOX content did not differ in the control and suicide groups but p5-LOX was significantly elevated in the suicide samples. The 5-LOX protein content was reduced in the membrane fraction and increased in the cytosol fraction of suicide victims. We propose that further studies of brain 5-LOX are needed to elucidate the functional implications of the protein alterations observed in our present study, and to further explore a putative role of 5-LOX in depression and suicide. PMID:19890443

  7. Task constraints modulate activation in right ventral lateral prefrontal cortex.

    Science.gov (United States)

    Vartanian, Oshin; Goel, Vinod

    2005-10-01

    Lesion data suggest that right prefrontal cortex (PFC) plays a critical role in open-ended problem solving. To test this hypothesis, we scanned fifteen normal subjects with fMRI as they completed three types of anagram problems varying in the level of constraints placed on the search space. On unconstrained trials, they rearranged letters to generate solutions (e.g., Can you make a "Word with ZJAZ?"). On semantically constrained trials, they rearranged letters to generate solutions within particular semantic categories (e.g., Can you make a type of "Music with ZJAZ?"). On baseline trials, they rearranged letters to make specific words (e.g., Can you make the word "JAZZ with ZJAZ?"). As predicted, the critical comparison of unconstrained vs. semantically constrained trials revealed significant activation in right ventral lateral PFC, as well as left superior frontal gyrus, frontopolar cortex, right superior parietal lobe, right post central gyrus, and the occipital-parietal sulcus. Furthermore, activation in right ventral lateral PFC (BA 47) increased as the constraints placed on the anagram search space were reduced. We argue that the activation in right ventral lateral PFC is related to hypothesis generation in unconstrained settings, whereas activation in other structures is related to additional processes linked to anagram problems such as semantic retrieval, semantic categorization, and cognitive monitoring. These results extend the lesion data and imaging studies by demonstrating that a relative absence of constraints on the solution space is sufficient to engage right ventral lateral PFC in hypothesis generation tasks.

  8. [Prefrontal activity and weekend alcoholism in the young].

    Science.gov (United States)

    García-Moreno, Luis Miguel; Expósito, Javier; Sanhueza, Claudia; Angulo, Ma Teresa

    2008-01-01

    High alcohol consumption by young people at weekends is a public health problem of considerable social and family importance. Chronic alcohol intake causes structural changes in the central nervous system, though the effects are not uniform throughout the brain. The prefrontal cortex (PC) has been reported to be one of the regions most sensitive to prolonged alcohol ingestion. The effects of chronic ethanol exposure have been extensively studied. Our aim is to identify the neuropsychological deficits in PC function induced by intermittent heavy alcohol drinking in young adults. Neuropsychological assessment was carried out on participants to examine their performance in PC-dependent tasks. 62 subjects (mean age 18.82+/-1.099) were assigned to one of three categories: 1) Those reporting heavy binge drinking of alcohol at weekends (ALE); 2) Those reporting moderate binge drinking of alcohol at weekends (ALM); and 3) Those reporting no alcohol intake (CTR). The findings indicate that intermittent alcohol binge drinking, either heavy or moderate, in young people results in poorer performance in neuropsychological tasks such as Digits, Corsi or Stroop, which depend on correct PC functioning. Our results support the claim that the binge pattern of exposure to ethanol leads to neurocognitive and neurobehavioural impairment equivalent, in many respects, to that found in chronic drinkers. Moreover, intermittent heavy alcohol drinking in adolescence and early adulthood increases the risks of lifetime alcohol dependence and other psychopathologies.

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

    Directory of Open Access Journals (Sweden)

    Anouk eVermeij

    2014-11-01

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

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

    Science.gov (United States)

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

    2008-03-01

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

  11. 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.

  12. Reversible antisocial behavior in ventromedial prefrontal lobe epilepsy.

    Science.gov (United States)

    Trebuchon, Agnès; Bartolomei, Fabrice; McGonigal, Aileen; Laguitton, Virginie; Chauvel, Patrick

    2013-11-01

    Frontal lobe dysfunction is known to be associated with impairment in social behavior. We investigated the link between severe pharmacoresistant frontal lobe epilepsy and antisocial trait. We studied four patients with pharmacoresistant epilepsy involving the prefrontal cortex, presenting abnormal interictal social behavior. Noninvasive investigations (video-EEG, PET, MRI) and intracerebral recording (stereoelectroencephalography (SEEG)) were performed as part of a presurgical assessment. Comprehensive psychiatric and cognitive evaluation was performed pre- and postoperatively for frontal lobe epilepsy, with at least 7years of follow-up. All patients shared a characteristic epilepsy pattern: (1) chronic severe prefrontal epilepsy with daily seizures and (2) an epileptogenic zone as defined by intracerebral recording involving the anterior cingulate cortex, ventromedial PFC, and the posterior part of the orbitofrontal cortex, with early propagation to contralateral prefrontal and ipsilateral medial temporal structures. All patients fulfilled the diagnostic criteria (DSM-IV) of antisocial personality disorder, which proved to be reversible following seizure control. Pharmacoresistant epilepsy involving a prefrontal network is associated with antisocial personality. We hypothesize that the occurrence of frequent seizures in this region over a prolonged period produces functional damage leading to impaired prefrontal control of social behavior. This functional damage is reversible since successful epilepsy surgery markedly improved antisocial behavior in these patients. The results are in line with previous reports of impairment of social and moral behavior following ventromedial frontal lobe injury. © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2011-08-15

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

  14. 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

  15. 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...... a locus in Brodmann's area 11 of the inferomedial prefrontal cortex (IMPC) at which these two separate measures had significant inverse correlation. Thus, under the specific circumstance of positron emission tomography (PET) of a pharmacological challenge, a key region of the inferomedial prefrontal...... 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....

  16. Specialization in the left prefrontal cortex for sentence comprehension.

    Science.gov (United States)

    Hashimoto, Ryuichiro; Sakai, Kuniyoshi L

    2002-08-01

    Using functional magnetic resonance imaging (fMRI), we examined cortical activation under syntactic decision tasks and a short-term memory task for sentences, focusing on essential properties of syntactic processing. By comparing activation in these tasks with a short-term memory task for word lists, we found that two regions in the left prefrontal cortex showed selective activation for syntactic processing: the dorsal prefrontal cortex (DPFC) and the inferior frontal gyrus (IFG). Moreover, the left DPFC showed more prominent activation under the short-term memory task for sentences than that for word lists, which cannot be explained by general cognitive factors such as task difficulty and verbal short-term memory. These results support the proposal of specialized systems for sentence comprehension in the left prefrontal cortex.

  17. Role of Prefrontal Persistent Activity in Working Memory

    Science.gov (United States)

    Riley, Mitchell R.; Constantinidis, Christos

    2016-01-01

    The prefrontal cortex is activated during working memory, as evidenced by fMRI results in human studies and neurophysiological recordings in animal models. Persistent activity during the delay period of working memory tasks, after the offset of stimuli that subjects are required to remember, has traditionally been thought of as the neural correlate of working memory. In the last few years several findings have cast doubt on the role of this activity. By some accounts, activity in other brain areas, such as the primary visual and posterior parietal cortex, is a better predictor of information maintained in visual working memory and working memory performance; dynamic patterns of activity may convey information without requiring persistent activity at all; and prefrontal neurons may be ill-suited to represent non-spatial information about the features and identity of remembered stimuli. Alternative interpretations about the role of the prefrontal cortex have thus been suggested, such as that it provides a top-down control of information represented in other brain areas, rather than maintaining a working memory trace itself. Here we review evidence for and against the role of prefrontal persistent activity, with a focus on visual neurophysiology. We show that persistent activity predicts behavioral parameters precisely in working memory tasks. We illustrate that prefrontal cortex represents features of stimuli other than their spatial location, and that this information is largely absent from early cortical areas during working memory. We examine memory models not dependent on persistent activity, and conclude that each of those models could mediate only a limited range of memory-dependent behaviors. We review activity decoded from brain areas other than the prefrontal cortex during working memory and demonstrate that these areas alone cannot mediate working memory maintenance, particularly in the presence of distractors. We finally discuss the discrepancy between

  18. Individual differences in moral judgment competence are related to activity of the prefrontal cortex when attributing blame to evil intention.

    Science.gov (United States)

    Li, Xiaojing; Yang, Juan; Li, Peng; Li, Hong

    2016-01-01

    The weighing of intentions and consequences is inconsistent in adult's moral judgments, and this is particularly prominent when assigning blame to the immoral intentions in the absence of negative outcomes. The current study extends previous research by examining how individual differences in moral judgment competence are reflected in the cortical network when making judgments about immoral intentions. Twenty-four participants were scanned, using functional magnetic resonance imaging, while making judgments about three kinds of moral scenarios: a neutral condition, an immoral intention condition, and an immoral condition. The result showed that comparing with making judgments about the other two conditions, making judgments about the immoral intentions takes longer time and was associated with significantly elevated activity in the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex. Additionally, moral judgment competence scores were inversely correlated with activity in the right dorsolateral prefrontal cortex when assigning blame to the immoral intentions. Greater activity in the right dorsolateral prefrontal cortex in participants with lower moral judgment competence possibly reflected increased recruitment of cognitive resource applied to control impulsive response and integrate competitive information in making judgments about the immoral intention.

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

    Directory of Open Access Journals (Sweden)

    Ryu Takizawa

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

  20. Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

    2017-03-15

    A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

  1. Top-Down Control of Motor Cortex Ensembles by Dorsomedial Prefrontal Cortex

    OpenAIRE

    Narayanan, Nandakumar S.; Laubach, Mark

    2006-01-01

    Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predi...

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  7. Implication on the Cytoarchitectural Profile of the Medial Prefrontal ...

    African Journals Online (AJOL)

    asus

    2017-11-12

    Nov 12, 2017 ... of the medial prefrontal cortex (mPFC) and cerebellar cortex; hence this study was aimed at evaluating ... It was observed from this study that exposure to Pentazocine-Alcohol combination triggers ..... violet stain in the molecular layer, though the Purkinje neurons are deeply stained, they have lost their.

  8. 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

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

    Science.gov (United States)

    Raos, Vassilis; Savaki, Helen E

    2017-10-01

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

  10. Histological evaluation of the prefrontal cortex of infantile Wistar rats ...

    African Journals Online (AJOL)

    Exposure to nicotine in utero is neuroteratogenic, predisposing the developing brain to cell injury and many forms of neurological and neurobehavioural problems that persist after birth. The current study examined some of the histological effects of prenatal nicotine exposure on the prefrontal cortex of infantile rats.

  11. The impact of social disparity on prefrontal function in childhood.

    Directory of Open Access Journals (Sweden)

    Margaret A Sheridan

    Full Text Available The prefrontal cortex (PFC develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children.

  12. 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

  13. Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

    Science.gov (United States)

    Cruse, Damian; Wilding, Edward L.

    2009-01-01

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

  14. 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…

  15. Phineas gauged: decision-making and the human prefrontal cortex

    NARCIS (Netherlands)

    Sanfey, A.G.; Hastie, R.; Colvin, M.K.; Grafman, J.

    2003-01-01

    Poor social judgment and decision-making abilities have often been attributed to people who have suffered injury to the ventromedial prefrontal cortex (VMPFC). However, few laboratory tests of decision-making have been conducted on these patients. The exception to this is the Iowa Gambling Task

  16. CB1 cannabinoid receptor stimulation during adolescence impairs the maturation of GABA function in the adult rat prefrontal cortex.

    Science.gov (United States)

    Cass, D K; Flores-Barrera, E; Thomases, D R; Vital, W F; Caballero, A; Tseng, K Y

    2014-05-01

    Converging epidemiological studies indicate that cannabis abuse during adolescence increases the risk of developing psychosis and prefrontal cortex (PFC)-dependent cognitive impairments later in life. However, the mechanisms underlying the adolescent susceptibility to chronic cannabis exposure are poorly understood. Given that the psychoactive constituent of cannabis binds to the CB1 cannabinoid receptor, the present study was designed to determine the impact of a CB1 receptor agonist (WIN) during specific windows of adolescence on the functional maturation of the rat PFC. By means of local field potential recordings and ventral hippocampal stimulation in vivo, we found that a history of WIN exposure during early (postnatal days - P35-40) or mid-(P40-45) adolescence, but not in late adolescence (P50-55) or adulthood (P75-80), is sufficient to yield a state of frequency-dependent prefrontal disinhibition in adulthood comparable to that seen in the juvenile PFC. Remarkably, this prefrontal disinhibition could be normalized following a single acute local infusion of the GABA-Aα1 positive allosteric modulator Indiplon, suggesting that adolescent exposure to WIN causes a functional downregulation of GABAergic transmission in the PFC. Accordingly, in vitro recordings from adult rats exposed to WIN during adolescence demonstrate that local prefrontal GABAergic transmission onto layer V pyramidal neurons is markedly reduced to the level seen in the P30-35 PFC. Together, these results indicate that early and mid-adolescence constitute a critical period during which repeated CB1 receptor stimulation is sufficient to elicit an enduring state of PFC network disinhibition resulting from a developmental impairment of local prefrontal GABAergic transmission.

  17. Fear Expression Suppresses Medial Prefrontal Cortical Firing in Rats.

    Directory of Open Access Journals (Sweden)

    Thomas F Giustino

    Full Text Available The medial prefrontal cortex (mPFC plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL and infralimbic (IL subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear. On Day 1, rats received either signaled or unsignaled footshocks in the recording chamber; an auditory conditioned stimulus (CS preceded signaled footshocks. Twenty-four hours later, animals were returned to the recording chamber (modified to create a novel context where they received 5 CS-alone trials. After fear conditioning, both signaled and unsignaled rats exhibited high levels of post-shock freezing that was associated with an enduring suppression of mPFC spontaneous firing, particularly in the IL of signaled rats. Twenty-four hours later, CS presentation produced differential conditioned freezing in signaled and unsignaled rats: freezing increased in rats that had received signaled shocks, but decreased in animals in the unsignaled condition (i.e., external inhibition. This group difference in CS-evoked freezing was mirrored in the spontaneous firing rate of neurons in both PL and IL. Interestingly, differences in PL and IL firing rate highly correlated with freezing levels. In other words, in the signaled group IL spontaneous rates were suppressed relative to PL, perhaps limiting IL-mediated suppression of fear and allowing PL activity to dominate performance, resulting in high levels of freezing. This was not observed in the unsignaled group, which exhibited low freezing. These data reveal that the activity of mPFC neurons is modulated by both

  18. Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

    Science.gov (United States)

    Späti, Jakub; Hänggi, Jürgen; Doerig, Nadja; Ernst, Jutta; Sambataro, Fabio; Brakowski, Janis; Jäncke, Lutz; grosse Holtforth, Martin; Seifritz, Erich; Spinelli, Simona

    2015-01-01

    Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment. PMID:25598428

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

    Directory of Open Access Journals (Sweden)

    Laura eMusazzi

    2015-04-01

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

  20. Catechol-O-methyltransferase Val158Met polymorphism influences prefrontal executive function in early Parkinson's disease.

    Science.gov (United States)

    Zhang, Youwen; Feng, Shujun; Nie, Kun; Zhao, Xin; Gan, Rong; Wang, Limin; Zhao, Jiehao; Tang, Hongmei; Gao, Liang; Zhu, Ruiming; Wang, Lijuan; Zhang, Yuhu

    2016-10-15

    The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to be associated with increased risk of Parkinson's disease (PD) and have a specific impact on dopamine-mediated prefrontal executive function in an inverted-U curve manner. We explored the influence of this genetic polymorphism on prefrontal executive function in a well-established Chinese cohort of early PD patients with no current or past history of motor fluctuations or dyskinesias. Cognitive functions were assessed in 250 patients with early PD using Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC). These patients and 300 healthy controls were subsequently genotyped for the COMT gene Val158Met polymorphism. We employed analysis of covariance (ANCOVA) and a stratified analysis to determine the associations between the COMT Val158Met genotype and cognitive functions. The COMT Val158Met allele frequency and genotype distributions showed no statistically significant differences between PD patients and controls. However, patients with met/met genotype performed significantly worse on WAIS-RC similarities, a measure of executive function, compared to individuals with val/val genotype. Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Further stratified analysis showed that the lower-activity COMT met/met genotype has a detrimental effect on executive function among women. Our results demonstrate that COMT Val158Met polymorphism is probably not associated with increased risk of PD, but has an effect on prefrontal executive function interacting with gender and dopaminergic medication. Copyright © 2016. Published by Elsevier B.V.

  1. Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

    Science.gov (United States)

    Birnbaum, S. G.; Yuan, P. X.; Wang, M.; Vijayraghavan, S.; Bloom, A. K.; Davis, D. J.; Gobeske, K. T.; Sweatt, J. D.; Manji, H. K.; Arnsten, A. F. T.

    2004-10-01

    The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

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

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

    2016-10-01

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

  3. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users.

    Science.gov (United States)

    Crunelle, Cleo L; Kaag, Anne Marije; van den Munkhof, Hanna E; Reneman, Liesbeth; Homberg, Judith R; Sabbe, Bernard; van den Brink, Wim; van Wingen, Guido

    2015-10-01

    Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal cortex in response to biologically salient stimuli in an emotional face matching task (EFMT). Amygdala activity and amygdala connectivity during the EFMT were assessed in 51 cocaine using males and 32 non-drug-using healthy males using functional magnetic resonance imaging (fMRI). Within the cocaine use group, we explored whether amygdala activation was associated with age of first use of cocaine and duration of cocaine use to distinguish between amygdala activation alterations as a cause or a consequence of cocaine use. We observed hyperactivity of the amygdala, thalamus, and hippocampus and reduced amygdala connectivity with the anterior cingulate gyrus in response to angry and fearful facial expressions in current cocaine users compared to controls. Increased amygdala activation was independently associated with earlier age of first cocaine use and with longer exposure to cocaine. Our findings suggest that amygdala hyperactivity to biologically salient stimuli may represent a risk factor for an early onset of cocaine use and that prolonged cocaine use may further sensitize amygdala activation. High amygdala activation to emotional face processing in current cocaine users may result from low prefrontal control of the amygdala response to such stimuli. © 2015 Wiley Periodicals, Inc.

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

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

    2015-02-01

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

  5. Self-reported sleep correlates with prefrontal-amygdala functional connectivity and emotional functioning.

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    Killgore, William D S

    2013-11-01

    Prior research suggests that sleep deprivation is associated with declines in some aspects of emotional intelligence and increased severity on indices of psychological disturbance. Sleep deprivation is also associated with reduced prefrontal-amygdala functional connectivity, potentially reflecting impaired top-down modulation of emotion. It remains unknown whether this modified connectivity may be observed in relation to more typical levels of sleep curtailment. We examined whether self-reported sleep duration the night before an assessment would be associated with these effects. Participants documented their hours of sleep from the previous night, completed the Bar-On Emotional Quotient Inventory (EQ-i), Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), and Personality Assessment Inventory (PAI), and underwent resting-state functional magnetic resonance imaging (fMRI). Outpatient neuroimaging center at a private psychiatric hospital. Sixty-five healthy adults (33 men, 32 women), ranging in age from 18-45 y. N/A. Greater self-reported sleep the preceding night was associated with higher scores on all scales of the EQ-i but not the MSCEIT, and with lower symptom severity scores on half of the psychopathology scales of the PAI. Longer sleep was also associated with stronger negative functional connectivity between the right ventromedial prefrontal cortex and amygdala. Moreover, greater negative connectivity between these regions was associated with higher EQ-i and lower symptom severity on the PAI. Self-reported sleep duration from the preceding night was negatively correlated with prefrontal-amygdala connectivity and the severity of subjective psychological distress, while positively correlated with higher perceived emotional intelligence. More sleep was associated with higher emotional and psychological strength.

  6. Dopamine regulates two classes of primate prefrontal neurons that represent sensory signals.

    Science.gov (United States)

    Jacob, Simon N; Ott, Torben; Nieder, Andreas

    2013-08-21

    The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing, is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms have been comprehensively studied in the context of short-term memory, but little is known about how DA regulates sensory inputs to PFC that precede and give rise to such memory activity. By preparing recipient cortical circuits for incoming signals, DA could be a powerful determinant of downstream cognitive processing. Here, we tested the hypothesis that prefrontal DA regulates the representation of sensory signals that are required for perceptual decisions. In rhesus monkeys trained to report the presence or absence of visual stimuli at varying levels of contrast, we simultaneously recorded extracellular single-unit activity and applied DA to the immediate vicinity of the neurons by micro-iontophoresis. We found that DA modulation of prefrontal neurons is not uniform but tailored to specialized neuronal classes. In one population of neurons, DA suppressed activity with high temporal precision but preserved signal/noise ratio. Neurons in this group had short visual response latencies and comprised all recorded narrow-spiking, putative interneurons. In a distinct population, DA increased excitability and enhanced signal/noise ratio by reducing response variability. These neurons had longer visual response latencies and were composed exclusively of broad-spiking, putative pyramidal neurons. By gating sensory inputs to PFC and subsequently strengthening the representation of sensory signals, DA might play an important role in shaping how the PFC initiates appropriate behavior in response to changes in the sensory environment.

  7. Domain expertise insulates against judgment bias by monetary favors through a modulation of ventromedial prefrontal cortex.

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    Kirk, Ulrich; Harvey, Ann; Montague, P Read

    2011-06-21

    Recent work using an art-viewing paradigm shows that monetary sponsorship of the experiment by a company (a favor) increases the valuation of paintings placed next to the sponsoring corporate logo, an effect that correlates with modulation of the ventromedial prefrontal cortex (VMPFC). We used the same art-viewing paradigm to test a prevailing idea in the domain of conflict-of-interest: that expertise in a domain insulates against judgment bias even in the presence of a monetary favor. Using a cohort of art experts, we show that monetary favors do not bias the experts' valuation of art, an effect that correlates with a lack of modulation of the VMPFC across sponsorship conditions. The lack of sponsorship effect in the VMPFC suggests the hypothesis that their brains remove the behavioral sponsorship effect by censoring sponsorship-dependent modulation of VMPFC activity. We tested the hypothesis that prefrontal regions play a regulatory role in mediating the sponsorship effect. We show that the dorsolateral prefrontal cortex (DLPFC) is recruited in the expert group. Furthermore, we tested the hypothesis in nonexpert controls by contrasting brain responses in controls who did not show a sponsorship effect to controls who did. Changes in effective connectivity between the DLPFC and VMPFC were greater in nonexpert controls, with an absence of the sponsorship effect relative to those with a presence of the sponsorship effect. The role of the DLPFC in cognitive control and emotion regulation suggests that it removes the influence of a monetary favor by controlling responses in known valuation regions of the brain including the the VMPFC.

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

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    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.

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

    Science.gov (United States)

    2011-01-01

    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. PMID:22085449

  10. Combined effect of prefrontal transcranial direct current stimulation and a working memory task on heart rate variability.

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    Stevan Nikolin

    Full Text Available Prefrontal cortex activity has been associated with changes to heart rate variability (HRV via mediation of the cortico-subcortical pathways that regulate the parasympathetic and sympathetic branches of the autonomic nervous system. Changes in HRV due to altered prefrontal cortex functioning can be predicted using the neurovisceral integration model, which suggests that prefrontal hyperactivity increases parasympathetic tone and decreases contributions from the sympathetic nervous system. Working memory (WM tasks and transcranial direct current stimulation (tDCS have been used independently to modulate brain activity demonstrating changes to HRV in agreement with the model. We investigated the combined effects of prefrontal tDCS and a WM task on HRV. Bifrontal tDCS was administered for 15 minutes at 2mA to 20 participants in a sham controlled, single-blind study using parallel groups. A WM task was completed by participants at three time points; pre-, during-, and post-tDCS, with resting state data collected at similar times. Frequency-domain HRV was computed for high frequency (HF; 0.15-0.4Hz and low frequency (LF; 0.04-0.15Hz power reflecting parasympathetic and sympathetic branch activity, respectively. Response time on the WM task, but not accuracy, improved from baseline to during-tDCS and post-tDCS with sham, but not active, stimulation. HF-HRV was significantly increased in the active tDCS group compared to sham, lasting beyond cessation of stimulation. Additionally, HF-HRV showed a task-related reduction in power during performance on the WM task. Changes in LF-HRV were moderately inversely correlated (r > 0.4 with changes in WM accuracy during and following tDCS compared to baseline levels. Stimulation of the prefrontal cortex resulted in changes to the parasympathetic branch of the nervous system in agreement with a linearly additive interpretation of effects. Sympathetic activity was not directly altered by tDCS, but was correlated

  11. Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

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    Raquel Viejo-Sobera

    2017-08-01

    Full Text Available Theta burst stimulation (TBS protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS or increase (intermittent, iTBS cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC are particularly interesting given its involvement in working memory (WM and executive functions (EF, often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi. To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently

  12. A TRANSLATIONAL INVESTIGATION TARGETING STRESS-REACTIVITY AND PRE-FRONTAL COGNITIVE CONTROL WITH GUANFACINE FOR SMOKING CESSATION

    Science.gov (United States)

    McKee, Sherry A.; Potenza, Marc N.; Kober, Hedy; Sofuoglu, Mehmet; Arnsten, Amy F. T.; Picciotto, Marina R.; Weinberger, Andrea H.; Ashare, Rebecca; Sinha, Rajita

    2015-01-01

    Stress and pre-frontal cognitive dysfunction have key roles in driving smoking, however, there are no therapeutics for smoking cessation which attenuate the effects of stress on smoking and enhance cognition. Central noradrenergic pathways are involved in stress-induced reinstatement to nicotine and in the prefrontal executive control of adaptive behaviors. We used a novel translational approach employing a validated laboratory analogue of stress-precipitated smoking, fMRI, and a proof-of-concept treatment period to evaluate whether the noradrenergic α2a agonist, guanfacine (3mg/day) versus placebo (0mg/day) reduced stress-precipitated smoking in the laboratory, altered cortico-striatal activation during the Stroop cognitive-control task, and reduced smoking following a quit attempt. In nicotine-deprived smokers (n=33), stress versus a neutral condition significantly decreased the latency to smoke, and increased tobacco craving, ad-libitum smoking, and systolic blood pressure in placebo-treated subjects, and these effects were absent or reduced in guanfacine-treated subjects. Following stress, placebo-treated subjects demonstrated decreased cortisol levels whereas guanfacine-treated subjects demonstrated increased levels. Guanfacine, compared to placebo, altered prefrontal activity during a cognitive control task, and reduced cigarette use but did not increase complete abstinence during treatment. These preliminary laboratory, neuroimaging and clinical outcome data were consistent and complementary and support further development of guanfacine for smoking cessation. PMID:25516371

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

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    Iroise Dumontheil

    2014-10-01

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

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

    Science.gov (United States)

    Dumontheil, Iroise

    2014-10-01

    Rostral prefrontal cortex (RPFC) has increased in size and changed in terms of its cellular organisation during primate evolution. In parallel emerged the ability to detach oneself from the immediate environment to process abstract thoughts and solve problems and to understand other individuals' thoughts and intentions. Rostrolateral prefrontal cortex (RLPFC) is thought to play an important role in supporting the integration of abstract, often self-generated, thoughts. Thoughts can be temporally abstract and relate to long term goals, or past or future events, or relationally abstract and focus on the relationships between representations rather than simple stimulus features. Behavioural studies have provided evidence of a prolonged development of the cognitive functions associated with RLPFC, in particular logical and relational reasoning, but also episodic memory retrieval and prospective memory. Functional and structural neuroimaging studies provide further support for a prolonged development of RLPFC during adolescence, with some evidence of increased specialisation of RLPFC activation for relational integration and aspects of episodic memory retrieval. Topics for future research will be discussed, such as the role of medial RPFC in processing abstract thoughts in the social domain, the possibility of training abstract thinking in the domain of reasoning, and links to education. Copyright © 2014. Published by Elsevier Ltd.

  15. Attention to Multiple Objects Facilitates Their Integration in Prefrontal and Parietal Cortex.

    Science.gov (United States)

    Kim, Yee-Joon; Tsai, Jeffrey J; Ojemann, Jeffrey; Verghese, Preeti

    2017-05-10

    stimuli increases the interaction component that is a hallmark for perceptual integration of stimuli. Furthermore, this stimulus-specific interaction is represented in prefrontal and parietal cortex in a task-dependent manner. Copyright © 2017 the authors 0270-6474/17/374942-12$15.00/0.

  16. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

    Science.gov (United States)

    Chakroborty, Shreaya; Geisbush, Thomas R.; Dale, Elena; Pehrson, Alan L.; Sánchez, Connie; West, Anthony R.

    2017-01-01

    Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v.) on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC), medial shell of the nucleus accumbens (msNAc), and lateral septal nucleus (LSN) in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF) inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI)] escitalopram (1.6 mg/kg, i.v.) to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups, indicating that

  17. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram

    Directory of Open Access Journals (Sweden)

    Shreaya Chakroborty

    2017-10-01

    Full Text Available Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC, however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v. on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC, medial shell of the nucleus accumbens (msNAc, and lateral septal nucleus (LSN in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI] escitalopram (1.6 mg/kg, i.v. to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups

  18. Impact of Vortioxetine on Synaptic Integration in Prefrontal-Subcortical Circuits: Comparisons with Escitalopram.

    Science.gov (United States)

    Chakroborty, Shreaya; Geisbush, Thomas R; Dale, Elena; Pehrson, Alan L; Sánchez, Connie; West, Anthony R

    2017-01-01

    Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear. Thus, the current study examined the impact of systemic vortioxetine administration (0.8 mg/kg, i.v.) on spontaneous spiking and spikes evoked by electrical stimulation of the mPFC in the anterior cingulate cortex (ACC), medial shell of the nucleus accumbens (msNAc), and lateral septal nucleus (LSN) in urethane-anesthetized rats. We also examined whether vortioxetine modulated afferent drive in the msNAc from hippocampal fimbria (HF) inputs. Similar studies were performed using the selective 5-HT reuptake inhibitor [selective serotonin reuptake inhibitors (SSRI)] escitalopram (1.6 mg/kg, i.v.) to enable comparisons between the multimodal actions of vortioxetine and SSRI-mediated effects. No significant differences in spontaneous activity were observed in the ACC, msNAc, and LSN across treatment groups. No significant impact of treatment on mPFC-evoked responses was observed in the ACC. In contrast, vortioxetine decreased mPFC-evoked activity recorded in the msNAc as compared to parallel studies in control and escitalopram treated groups. Thus, vortioxetine may reduce mPFC-msNAc afferent drive via a mechanism that, in addition to an SSRI-like effect, requires 5-HT receptor modulation. Recordings in the LSN revealed a significant increase in mPFC-evoked activity following escitalopram administration as compared to control and vortioxetine treated groups, indicating that

  19. Compulsive Sexual Behavior: Prefrontal and Limbic Volume and Interactions

    DEFF Research Database (Denmark)

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

    2017-01-01

    Background: Compulsive sexual behaviors (CSB) are relatively common and associated with significant personal and social dysfunction. The underlying neurobiology is still poorly understood. The present study examines brain volumes and resting state functional connectivity in CSB compared...... with matched healthy volunteers (HV). Methods: Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were...... prefrontal cortex (whole brain, cluster corrected FWE P compared with HV. Conclusions: CSB is associated with elevated volumes in limbic regions relevant to motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions...

  20. Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2011-07-01

    Full Text Available "nThe purpose of the present study was to determine the role of medial prefrontal cortex (mPFC dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH and antagonist, clozapine (CLZ into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then exposed to the tone alone. Freezing responses were measured as conditioned fear index. The results showed that both AMPH and CLZ infusion in mPFC reduced the expression of conditioned fear. This finding indicates that elevation or reduction in the dopaminergic activity is associated with the decrease of fear responses, despite preexisting individual-typological differences.

  1. Discourse production following injury to the dorsolateral prefrontal cortex.

    Science.gov (United States)

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

    2012-12-01

    Individuals with damage to the prefrontal cortex, and the dorsolateral prefrontal cortex (DLPFC) in particular, often demonstrate difficulties with the formulation of complex language not attributable to aphasia. The present study employed a discourse analysis procedure to characterize the language of individuals with left (L) or right (R) DLPFC lesions. All participants were 30-35 years post-onset of injury and presented with persistent discourse impairments. The discourse performance of the R DLPFC group was not significantly different from either the L DLPFC group or the non-injured comparison group. Individuals from the L DLPFC group demonstrated specific difficulties with narrative coherence and inclusion of critical story components. Both measures were significantly different from the comparison group. The discourse ability of the DLPFC groups was significantly correlated with measures of working memory. Findings support the use of discourse analysis for examining language impairments in individuals with PFC lesions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Prefrontal Cortex in Learning to Overcome Generalized Fear

    OpenAIRE

    Edward Korzus

    2015-01-01

    Normal brain functioning relies critically on the ability to control appropriate behavioral responses to fearful stimuli. Overgeneralized fear is the major symptom of anxiety disorders including posttraumatic stress disorder. This review describes recent data demonstrating that the medial prefrontal cortex (mPFC) plays a critical role in the refining of cues that drive the acquisition of fear response. Recent studies on molecular mechanisms that underlie the role of mPFC in fear discriminatio...

  3. Exploring prefrontal cortical memory mechanisms with eyeblink conditioning.

    Science.gov (United States)

    Weiss, Craig; Disterhoft, John F

    2011-06-01

    Several studies in nonhuman primates have shown that neurons in the dorsolateral prefrontal cortex have activity that persists throughout the delay period in delayed matching to sample tasks, and age-related changes in the microcolumnar organization of the prefrontal cortex are significantly correlated with age-related declines in cognition. Activity that persists beyond the presentation of a stimulus could mediate working memory processes, and disruption of those processes could account for memory deficits that often accompany the aging process. These potential memory and aging mechanisms are being systematically examined with eyeblink conditioning paradigms in nonprimate mammalian animal models including the rabbit. The trace version of the conditioning paradigm is a particularly good system to explore declarative memory since humans do not acquire trace conditioning if they are unable to become cognitively aware of the association between a conditioning tone and an airpuff to the eye. This conditioning paradigm has been used to show that the hippocampus and cerebellum interact functionally since both conditioned responses and conditioned hippocampal pyramidal neuron activity are abolished following lesions of the cerebellar nuclei and since hippocampal lesions prevent or abolish trace conditioned blinks. However, because there are no direct connections between the hippocampal formation and the cerebellum, and because the hippocampus is not necessary for trace conditioning after a period of consolidation has elapsed, we and others have been examining the prefrontal cortex for its role in forebrain-dependent trace eyeblink conditioning. This review examines some of the literature which suggests that the prefrontal cortex serves to orchestrate a neuronal network that interacts with the cerebellum to mediate adaptively timed conditioned responses.

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

    NARCIS (Netherlands)

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

    1982-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2015-11-01

    The projections from the amygdala and hippocampus (including subiculum and presubiculum) to prefrontal cortex were compared using anterograde tracers injected into macaque monkeys (Macaca fascicularis, Macaca mulatta). Almost all prefrontal areas were found to receive some amygdala inputs. These connections, which predominantly arose from the intermediate and magnocellular basal nucleus, were particularly dense in parts of the medial and orbital prefrontal cortex. Contralateral inputs were not, however, observed. The hippocampal projections to prefrontal areas were far more restricted, being confined to the ipsilateral medial and orbital prefrontal cortex (within areas 11, 13, 14, 24a, 32, and 25). These hippocampal projections principally arose from the subiculum, with the fornix providing the sole route. Thus, while the lateral prefrontal cortex essentially receives only amygdala inputs, the orbital prefrontal cortex receives both amygdala and hippocampal inputs, though these typically target different areas. Only in medial prefrontal cortex do direct inputs from both structures terminate in common sites. But, even when convergence occurs within an area, the projections predominantly terminate in different lamina (hippocampal inputs to layer III and amygdala inputs to layers I, II, and VI). The resulting segregation of prefrontal inputs could enable the parallel processing of different information types in prefrontal cortex. © The Author 2015. Published by Oxford University Press.

  7. 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

    2012-01-01

    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 also 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 corticocortical

  8. The effects of serotonin modulation on medial prefrontal connectivity strength and stability: A pharmacological fMRI study with citalopram.

    Science.gov (United States)

    Arnone, D; Wise, T; Walker, C; Cowen, P J; Howes, O; Selvaraj, S

    2018-01-31

    Static and dynamic functional connectivity are being increasingly used to measure the effects of disease and a range of different interventions on brain networks. While preliminary evidence suggests that static connectivity can be modulated by chronic antidepressants administration in healthy individuals and in major depression, much less is known about the acute effects of antidepressants especially on dynamic functional connectivity changes. Here we examine acute effects of antidepressants on dynamic functional connectivity within the default mode network. The default mode network is a well described network with many functions in which the role of serotonin is not clear. In this work we measured acute pharmacological effects of an infusion of the selective serotonin reuptake inhibitor (SSRI) citalopram 10 mg in a sample of thirteen healthy volunteers randomised to receive on two occasions the active compound or placebo in a cross over dosing. Acute citalopram administration relative to placebo increased static connectivity between the medial prefrontal cortex and right dorsolateral prefrontal cortex and posterior cingulate cortex. The SSRI also induced a reduction in variability of connectivity with the medial prefrontal cortex in the precuneus and posterior cingulate cortex. The measured changes are compatible with modified serotonin cortical availability. Copyright © 2017. Published by Elsevier Inc.

  9. Association of Oxytocin and Parental Prefrontal Activation during Reunion with Infant: A Functional Near-Infrared Spectroscopy Study

    Directory of Open Access Journals (Sweden)

    Jun Ito

    2017-12-01

    Full Text Available Although previous studies have revealed the role of oxytocin (OT in parental behavior, the role of OT has not been investigated through the direct assessment of prefrontal brain activation during parenting. By using functional near-infrared spectroscopy, we aimed to show the relationship between parental [maternal (N = 15 and paternal (N = 21] OT levels and the activation of the prefrontal cortex (PFC, while holding their infants after separation. Baseline OT levels were measured in the subjects’ saliva samples before the experiment. Prefrontal brain activation was assessed in participants sitting alone on a chair (i.e., separation from their infant for 120 s and during the target period (i.e., holding their infant for 45 s, which was done in triplicate. The oxygen hemoglobin (oxy-Hb dissociation curve significantly increased in 9 out of 22 channels on the PFC when maternal and paternal samples were combined. However, only the fathers showed a correlation between salivary OT and oxy-Hb signal. Furthermore, while holding their infants, high-OT fathers showed left hemispheric dominance compared to low-OT fathers, while high-OT mothers showed right hemispheric dominance compared to low-OT mothers. This study showed that fathers with high-OT levels showed neural activation with left hemispheric dominance, while holding their infants, suggesting that increase of OT level might activate paternal PFC related to parenting behavior, although the same is not true for mothers.

  10. Does rTMS alter neurocognitive functioning in patients with panic disorder/agoraphobia? An fNIRS-based investigation of prefrontal activation during a cognitive task and its modulation via sham-controlled rTMS.

    Science.gov (United States)

    Deppermann, Saskia; Vennewald, Nadja; Diemer, Julia; Sickinger, Stephanie; Haeussinger, Florian B; Notzon, Swantje; Laeger, Inga; Arolt, Volker; Ehlis, Ann-Christine; Zwanzger, Peter; Fallgatter, Andreas J

    2014-01-01

    Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an "add-on" to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

  11. Does rTMS Alter Neurocognitive Functioning in Patients with Panic Disorder/Agoraphobia? An fNIRS-Based Investigation of Prefrontal Activation during a Cognitive Task and Its Modulation via Sham-Controlled rTMS

    Directory of Open Access Journals (Sweden)

    Saskia Deppermann

    2014-01-01

    Full Text Available Objectives. Neurobiologically, panic disorder (PD is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS, we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC could be replicated. As intermittent theta burst stimulation (iTBS modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG during the phonological task was found. Conclusion. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

  12. An fNIRS investigation of associative recognition in the prefrontal cortex with a rapid event-related design.

    Science.gov (United States)

    Schaeffer, James D; Yennu, Amarnath S; Gandy, Kellen C; Tian, Fenghua; Liu, Hanli; Park, Heekyeong

    2014-09-30

    Functional near-infrared spectroscopy (fNIRS) measures hemodynamic changes at the cortical level. The use of fNIRS is growing in popularity for studying cognitive neuroscience in which event-related designs are widely used with functional magnetic resonance imaging (fMRI). However, the applicability of event-related designs with fNIRS has not been fully understood. Therefore, the present study employed fNIRS with a rapid-presentation event-related design for investigating prefrontal cortical activity during complex associative recognition. Participants studied a list of word pairs and were later given an associative recognition test. Throughout the experiment, each event was presented rapidly (∼4s). Data were sorted based on accuracy of associative memory judgments and analyzed using the general linear model (GLM) with an event-related design. During retrieval, significant increases in oxygenated hemoglobin concentrations were observed in dorsolateral and ventrolateral prefrontal regions for successful associative recognition. When comparing retrieval to encoding, significant increases in oxygenated hemoglobin concentrations were also observed in dorsolateral prefrontal cortex. The current fNIRS results corroborate previous fMRI findings that have demonstrated the involvement of dorsolateral and ventrolateral prefrontal cortex in associative recognition. Therefore, the present study validates versatile use of fNIRS with a rapid-presentation event-related design in the investigation of neural mechanisms of associative memory. The findings of this study provide evidence that fNIRS can be a viable research method for investigating complex cognitive processes commonly of interest in cognitive neuroscience. Taken together, these results demonstrate that fNIRS can be a cost-effective and accessible experimental tool for cognitive neuroscience. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Effects of Food and Water Deprivation on Self-Stimulation of the Medial and Sulcal Prefrontal Cortex and Caudate Putamen in the Rat

    NARCIS (Netherlands)

    Koolhaas, J.M.; Mora, F.; Phillips, A.G.

    1977-01-01

    Self-stimulation rates from electrodes, implanted in the terminal areas of the mesocortical and nigrostriatal dopaminergic systems, were measured during food or water deprivation. A significant increase of sulcal prefrontal cortex self-stimulation was observed after 24 and 48 hr of food deprivation.

  14. Modulation of the action of stress by ethanol on dopaminergic activity in the rat prefrontal cortex

    Energy Technology Data Exchange (ETDEWEB)

    Hegarty, A.A.; Vogel, W.H. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1992-02-26

    Both stress and ethanol, when administered individually, have been shown to affect dopamine (DA) and its metabolite (DOPAC) in the central nervous system. Stress can increase DA efflux in several areas of the brain, whereas ethanol has been shown to have variable effects on extracellular DA, either increasing DA or having no apparent effect. Furthermore, ethanol has been shown in microdissection studies to antagonize the effect of stress on the dopaminergic system, indicating an anxiety-reducing property of ethanol. However, the influence of the combination of stress and ethanol on the dopaminergic system has not been studied extensively with the newer technique of microdialysis. In this study, microdialysis was again used to characterize the interaction of immobilization stress and ethanol in the prefrontal cortex. Two groups of rats received either ethanol or saline in the resting state. A third group was immobilization stress and ethanol in the prefrontal cortex. Two groups of rats received either ethanol or saline in the resting state. A third group was immobilization Saline-treated animals showed essentially no changes in levels of DA or DOPAC. Ethanol had no effect on DA overflow in resting animals and caused only a small increase in DOPAC levels. Immobilization caused marked increases in DA levels and smaller increases in DOPAC. Ethanol pretreatment strongly reduced and antagonized the stress-induced increases in DA. However, ethanol potentiated the stress-induced increase in extracellular DOPAC. The authors data add biochemical evidence to the tension-reduction hypothesis of ethanol by perhaps implicating a reduction in the DA stress response by ethanol as a contributing factor in the development of alcoholism.

  15. Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.

    Science.gov (United States)

    Birn, R M; Shackman, A J; Oler, J A; Williams, L E; McFarlin, D R; Rogers, G M; Shelton, S E; Alexander, A L; Pine, D S; Slattery, M J; Davidson, R J; Fox, A S; Kalin, N H

    2014-08-01

    Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.

  16. Reduction hybrid artifacts of EMG-EOG in electroencephalography evoked by prefrontal transcranial magnetic stimulation

    Science.gov (United States)

    Bai, Yang; Wan, Xiaohong; Zeng, Ke; Ni, Yinmei; Qiu, Lirong; Li, Xiaoli

    2016-12-01

    Objective. When prefrontal-transcranial magnetic stimulation (p-TMS) performed, it may evoke hybrid artifact mixed with muscle activity and blink activity in EEG recordings. Reducing this kind of hybrid artifact challenges the traditional preprocessing methods. We aim to explore method for the p-TMS evoked hybrid artifact removal. Approach. We propose a novel method used as independent component analysis (ICA) post processing to reduce the p-TMS evoked hybrid artifact. Ensemble empirical mode decomposition (EEMD) was used to decompose signal into multi-components, then the components were separated with artifact reduced by blind source separation (BSS) method. Three standard BSS methods, ICA, independent vector analysis, and canonical correlation analysis (CCA) were tested. Main results. Synthetic results showed that EEMD-CCA outperformed others as ICA post processing step in hybrid artifacts reduction. Its superiority was clearer when signal to noise ratio (SNR) was lower. In application to real experiment, SNR can be significantly increased and the p-TMS evoked potential could be recovered from hybrid artifact contaminated signal. Our proposed method can effectively reduce the p-TMS evoked hybrid artifacts. Significance. Our proposed method may facilitate future prefrontal TMS-EEG researches.

  17. Compromised Prefrontal Cognitive Control Over Emotional Interference in Adolescents with Internet Gaming Disorder.

    Science.gov (United States)

    Lee, Junghan; Lee, Seojung; Chun, Ji Won; Cho, Hyun; Kim, Dai-jin; Jung, Young-Chul

    2015-11-01

    Increased reports of impulsivity and aggression in male adolescents with Internet gaming might reflect their dysfunction in emotion regulation, particularly in suppression of negative emotions, which should affect the various stages of Internet gaming disorder. This study tested the hypothesis that adolescents with Internet gaming disorder would be more disturbed by the emotional interference and demonstrate compromised dorsal anterior cingulate cortex (dACC) activation during a Stroop Match-to-Sample task. In addition, functional connectivity analysis was conducted to examine the interplays between neural correlates involved in emotional processing and how they were altered in adolescents with Internet gaming disorder. The Internet gaming disorder group demonstrated weaker dACC activation and stronger insular activations to interfering angry facial stimuli compared with the healthy control group. Negative functional connectivity between stronger insular activation and weaker dorsolateral prefrontal activation correlated with higher cognitive impulsivity in adolescents with Internet gaming disorder. These findings provide evidence of the compromised prefrontal cognitive control over emotional interference in adolescents with Internet gaming disorder.

  18. Empathy for pain-related dorsolateral prefrontal activity is modulated by angry face perception.

    Science.gov (United States)

    Enzi, Björn; Amirie, Scharbanu; Brüne, Martin

    2016-11-01

    Empathy, i.e., the ability to perceive and share another person's affective state, is associated with activity in a complex neural network, including the anterior insula, the anterior and mid-cingulate cortex, and the lateral prefrontal cortex. Here, we were interested in the question how facial emotions influence the activation of the 'pain network'. In the present study, we used functional magnetic resonance imaging to investigate the neuronal correlates of empathy for pain and its interaction with emotional face recognition in 20 healthy subjects. We identified various brain regions commonly associated with empathy for pain, including the right mid-cingulate cortex, the left anterior insula (AI), and the left dorsolateral prefrontal cortex (dlPFC), with an increased neuronal response in the left dlPFC after the presentation of angry faces. Furthermore, a negative correlation between psychological measures of alexithymia and empathy for pain-related brain activity was observed in the left AI. The dlPFC is an important brain region involved in cognitive reappraisal or in 'top-down' control of the limbic system. Our findings could therefore reflect a regulatory response associated with distancing from negatively valenced stimuli. Moreover, our results underline the involvement of the AI in empathy for pain responses and their relationship to alexithymia.

  19. "God has sent me to you": Right temporal epilepsy, left prefrontal psychosis.

    Science.gov (United States)

    Arzy, Shahar; Schurr, Roey

    2016-07-01

    Religious experiences have long been documented in patients with epilepsy, though their exact underlying neural mechanisms are still unclear. Here, we had the rare opportunity to record a delusional religious conversion in real time in a patient with right temporal lobe epilepsy undergoing continuous video-EEG. In this patient, a messianic revelation experience occurred several hours after a complex partial seizure of temporal origin, compatible with postictal psychosis (PIP). We analyzed the recorded resting-state EEG epochs separately for each of the conventional frequency bands. Topographical analysis of the bandpass filtered EEG epochs revealed increased activity in the low-gamma range (30-40Hz) during religious conversion compared with activity during the patient's habitual state. The brain generator underlying this activity was localized to the left prefrontal cortex. This suggests that religious conversion in PIP is related to control mechanisms in the prefrontal lobe-related processes rather than medial temporal lobe-related processes. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Mental workload and neural efficiency quantified in the prefrontal cortex using fNIRS.

    Science.gov (United States)

    Causse, Mickaël; Chua, Zarrin; Peysakhovich, Vsevolod; Del Campo, Natalia; Matton, Nadine

    2017-07-12

    An improved understanding of how the brain allocates mental resources as a function of task difficulty is critical for enhancing human performance. Functional near infrared spectroscopy (fNIRS) is a field-deployable optical brain monitoring technology that provides a direct measure of cerebral blood flow in response to cognitive activity. We found that fNIRS was sensitive to variations in task difficulty in both real-life (flight simulator) and laboratory settings (tests measuring executive functions), showing increased concentration of oxygenated hemoglobin (HbO2) and decreased concentration of deoxygenated hemoglobin (HHb) in the prefrontal cortex as the tasks became more complex. Intensity of prefrontal activation (HbO2 concentration) was not clearly correlated to task performance. Rather, activation intensity shed insight on the level of mental effort, i.e., how hard an individual was working to accomplish a task. When combined with performance, fNIRS provided an estimate of the participants' neural efficiency, and this efficiency was consistent across levels of difficulty of the same task. Overall, our data support the suitability of fNIRS to assess the mental effort related to human operations and represents a promising tool for the measurement of neural efficiency in other contexts such as training programs or the clinical setting.

  1. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

    Science.gov (United States)

    Paret, Christian; Ruf, Matthias; Gerchen, Martin Fungisai; Kluetsch, Rosemarie; Demirakca, Traute; Jungkunz, Martin; Bertsch, Katja; Schmahl, Christian; Ende, Gabriele

    2016-01-15

    Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: pneurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The role of prefrontal cortex in visuo-spatial planning: A repetitive TMS study.

    Science.gov (United States)

    Basso, Demis; Lotze, Martin; Vitale, Lavinia; Ferreri, Florinda; Bisiacchi, Patrizia; Olivetti Belardinelli, Marta; Rossini, Paolo Maria; Birbaumer, Niels

    2006-05-01

    The visuo-spatial planning process is based on an "opportunistic" combination of heuristics and strategies, carried out in small units during the execution of plans. In order to investigate the functional role of the prefrontal cortex in heuristic switching, 42 healthy controls performed a labyrinth crossing task (the Maps Test). During this computerized version of the Travelling Salesperson Problem, subjects had to decide which order of locations optimizes total travel time and distance. This task was performed with and without 1 Hz repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the targeted area, applied during the task over bilateral frontal sites (active stimulation) and parieto-occipital site (sham stimulation). Only repetitive bilateral rTMS over F3 and F4 significantly decreased the number of strategies with changes of heuristics, and increased the number of movements required to solve the task. This behaviour contrasts with the performance of healthy subjects in the planning task, but is consistent with the performance of frontal traumatic brain injury patients. The results indicate that, in a visuo-spatial problem-solving task, the prefrontal cortex is involved in the switching between heuristics during the execution of a plan.

  3. Age differences in medial prefrontal activity for subsequent memory of truth value

    Science.gov (United States)

    Cassidy, Brittany S.; Hedden, Trey; Yoon, Carolyn; Gutchess, Angela H.

    2014-01-01

    Much research has demonstrated that aging is marked by decreased source memory relative to young adults, yet a smaller body of work has demonstrated that increasing the socioemotional content of source information may be one way to reduce age-related performance differences. Although dorsomedial prefrontal cortex (dmPFC) activity may support source memory among young and older adults, the extent to which one activates dorsal vs. ventral mPFC may reflect one's personal connection with incoming information. Because truth value may be one salient marker that impacts one's connection with information and allocation of attention toward incoming material, we investigated whether the perceived truth value of information differently impacts differences in mPFC activity associated with encoding source information, particularly with age. Twelve young (18–23 years) and 12 older adults (63–80 years) encoded true and false statements. Behavioral results showed similar memory performance between the age groups. With respect to neural activity associated with subsequent memory, young adults, relative to older adults, exhibited greater activity in dmPFC while older adults displayed enhanced ventromedial prefrontal cortex (vmPFC) and insula engagement relative to young. These results may potentially indicate that young adults focus on a general knowledge acquisition goal, while older adults focus on emotionally relevant aspects of the material. The findings demonstrate that age-related differences in recruitment of mPFC associated with encoding source information may in some circumstances underlie age-equivalent behavioral performance. PMID:24570672

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

    Science.gov (United States)

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

    2013-11-01

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

  5. Developmental Ethanol Exposure Leads to Long-Term Deficits in Attention and Its Underlying Prefrontal Circuitry.

    Science.gov (United States)

    Louth, Emma L; Bignell, Warren; Taylor, Christine L; Bailey, Craig D C

    2016-01-01

    Chronic prenatal exposure to ethanol can lead to a spectrum of teratogenic outcomes that are classified in humans as fetal alcohol spectrum disorders (FASD). One of the most prevalent and persistent neurocognitive components of FASD is attention deficits, and it is now thought that these attention deficits differ from traditional attention deficit hyperactivity disorder (ADHD) in their quality and response to medication. However, the neuronal mechanisms underlying attention deficits in FASD are not well understood. We show here that after developmental binge-pattern ethanol exposure, adult mice exhibit impaired performance on the five-choice serial reaction time test for visual attention, with lower accuracy during initial training and a higher rate of omissions under challenging conditions of high attention demand. Whole-cell electrophysiology experiments in these same mice find dysregulated pyramidal neurons in layer VI of the medial prefrontal cortex, which are critical for normal attention performance. Layer VI neurons show decreased intrinsic excitability and increased responses to stimulation of both nicotinic acetylcholine receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. Moreover, although nicotinic acetylcholine responses correlate with performance on the five-choice task in control mice, these relationships are completely disrupted in mice exposed to ethanol during development. These findings demonstrate a novel outcome of developmental binge-pattern ethanol exposure and suggest that persistent alterations to the function of prefrontal layer VI neurons play an important mechanistic role in attention deficits associated with FASD.

  6. Prefrontal neurons represent winning and losing during competitive video shooting games between monkeys.

    Science.gov (United States)

    Hosokawa, Takayuki; Watanabe, Masataka

    2012-05-30

    Humans and animals must work to support their survival and reproductive needs. Because resources are limited in the natural environment, competition is inevitable, and competing successfully is vitally important. However, the neuronal mechanisms of competitive behavior are poorly studied. We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment.

  7. Altered prefrontal glutamate-glutamine-gamma-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus.

    Science.gov (United States)

    Lyoo, In Kyoon; Yoon, Sujung J; Musen, Gail; Simonson, Donald C; Weinger, Katie; Bolo, Nicolas; Ryan, Christopher M; Kim, Jieun E; Renshaw, Perry F; Jacobson, Alan M

    2009-08-01

    Neural substrates for low cognitive performance and depression, common long-term central nervous system-related changes in patients with type 1 diabetes mellitus, have not yet been studied. To investigate whether prefrontal glutamate levels are higher in patients with type 1 diabetes and whether an elevation is related to lower cognitive performance and depression. Cross-sectional study. General clinical research center. One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants. With the use of proton magnetic resonance spectroscopy, prefrontal glutamate-glutamine-gamma-aminobutyric acid (Glx) levels were compared between patients and control subjects. Relationships between prefrontal Glx levels and cognitive function and between Glx levels and mild depressive symptoms were assessed in patients with type 1 diabetes. Prefrontal Glx concentrations were 9.0% (0.742 mmol/L; P = .005) higher in adult patients with type 1 diabetes than in healthy control subjects. There were positive linear trends for the effects of lifetime glycemic control on prefrontal Glx levels (P for trend = .002). Cognitive performances in memory, executive function, and psychomotor speed were lower in patients (P = .003, .01, and performance in assessment of global cognitive function (0.11 change in z score per 1-mmol/L increase in Glx) as well as with mild depression. The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system-related changes in patients with adult type 1 diabetes.

  8. Ethanol regulation of serum glucocorticoid kinase 1 expression in DBA2/J mouse prefrontal cortex.

    Science.gov (United States)

    Costin, Blair N; Dever, Seth M; Miles, Michael F

    2013-01-01

    We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1 regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions on the HPA axis. Acute ethanol increased Sgk1 mRNA expression in a dose and time dependent manner. Three separate results suggested that ethanol regulated Sgk1 via circulating glucocorticoids: acute ethanol increased glucocorticoid receptor binding to the Sgk1 promoter; adrenalectomy blocked ethanol induction of Sgk1 mRNA; and chronic ethanol exposure during locomotor sensitization down-regulated HPA axis activation and Sgk1 induction by acute ethanol. SGK1 protein had complex temporal responses to acute ethanol with rapid and transient increases in Ser422 phosphorylation at 15 min. following ethanol administration. This activating phosphorylation had functional consequences, as suggested by increased phosphorylation of the known SGK1 target, N-myc downstream-regulated gene 1 (NDRG1). After repeated ethanol administration during locomotor sensitization, basal SGK1 protein phosphorylation increased despite blunting of Sgk1 mRNA induction by ethanol. These results suggest that HPA axis and glucocorticoid receptor signaling mediate acute ethanol induction of Sgk1 transcription in mouse prefrontal cortex. However, acute ethanol also causes complex changes in SGK1 protein expression and activity. Chronic ethanol modifies both SGK1 protein and

  9. Ethanol Regulation of Serum Glucocorticoid Kinase 1 Expression in DBA2/J Mouse Prefrontal Cortex

    Science.gov (United States)

    Costin, Blair N.; Dever, Seth M.; Miles, Michael F.

    2013-01-01

    Background We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1 regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions on the HPA axis. Results Acute ethanol increased Sgk1 mRNA expression in a dose and time dependent manner. Three separate results suggested that ethanol regulated Sgk1 via circulating glucocorticoids: acute ethanol increased glucocorticoid receptor binding to the Sgk1 promoter; adrenalectomy blocked ethanol induction of Sgk1 mRNA; and chronic ethanol exposure during locomotor sensitization down-regulated HPA axis activation and Sgk1 induction by acute ethanol. SGK1 protein had complex temporal responses to acute ethanol with rapid and transient increases in Ser422 phosphorylation at 15 min. following ethanol administration. This activating phosphorylation had functional consequences, as suggested by increased phosphorylation of the known SGK1 target, N-myc downstream-regulated gene 1 (NDRG1). After repeated ethanol administration during locomotor sensitization, basal SGK1 protein phosphorylation increased despite blunting of Sgk1 mRNA induction by ethanol. Conclusions These results suggest that HPA axis and glucocorticoid receptor signaling mediate acute ethanol induction of Sgk1 transcription in mouse prefrontal cortex. However, acute ethanol also causes complex changes in SGK1 protein expression and activity. Chronic ethanol

  10. Is less really more: Does a prefrontal efficiency genotype actually confer better performance when working memory becomes difficult?

    Science.gov (United States)

    Ihne, Jessica L; Gallagher, Natalie M; Sullivan, Marie; Callicott, Joseph H; Green, Adam E

    2016-01-01

    Perhaps the most widely studied effect to emerge from the combination of neuroimaging and human genetics is the association of the COMT-Val(108/158)Met polymorphism with prefrontal activity during working memory. COMT-Val is a putative risk factor in schizophrenia, which is characterized by disordered prefrontal function. Work in healthy populations has sought to characterize mechanisms by which the valine (Val) allele may lead to disadvantaged prefrontal cognition. Lower activity in methionine (Met) carriers has been interpreted as advantageous neural efficiency. Notably, however, studies reporting COMT effects on neural efficiency have generally not reported working memory performance effects. Those studies have employed relatively low/easy working memory loads. Higher loads are known to elicit individual differences in working memory performance that are not visible at lower loads. If COMT-Met confers greater neural efficiency when working memory is easy, a reasonable prediction is that Met carriers will be better able to cope with increasing demand for neural resources when working memory becomes difficult. To our knowledge, this prediction has thus far gone untested. Here, we tested performance on three working memory tasks. Performance on each task was measured at multiple levels of load/difficulty, including loads more demanding than those used in prior studies. We found no genotype-by-load interactions or main effects of COMT genotype on accuracy or reaction time. Indeed, even testing for performance differences at each load of each task failed to find a single significant effect of COMT genotype. Thus, even if COMT genotype has the effects on prefrontal efficiency that prior work has suggested, such effects may not directly impact high-load working memory ability. The present findings accord with previous evidence that behavioral effects of COMT are small or nonexistent and, more broadly, with a growing consensus that substantial effects on phenotype will

  11. Effect of stimulation by foliage plant display images on prefrontal cortex activity: a comparison with stimulation using actual foliage plants.

    Science.gov (United States)

    Igarashi, Miho; Song, Chorong; Ikei, Harumi; Miyazaki, Yoshifumi

    2015-01-01

    Natural scenes like forests and flowers evoke neurophysiological responses that can suppress anxiety and relieve stress. We examined whether images of natural objects can elicit neural responses similar to those evoked by real objects by comparing the activation of the prefrontal cortex during presentation of real foliage plants with a projected image of the same foliage plants. Oxy-hemoglobin concentrations in the prefrontal cortex were measured using time-resolved near-infrared spectroscopy while the subjects viewed the real plants or a projected image of the same plants. Compared with a projected image of foliage plants, viewing the actual foliage plants significantly increased oxy-hemoglobin concentrations in the prefrontal cortex. However, using the modified semantic differential method, subjective emotional response ratings ("comfortable vs. uncomfortable" and "relaxed vs. awakening") were similar for both stimuli. The frontal cortex responded differently to presentation of actual plants compared with images of these plants even when the subjective emotional response was similar. These results may help explain the physical and mental health benefits of urban, domestic, and workplace foliage. © 2014 The Authors. Journal of Neuroimaging published by the American Society of Neuroimaging.

  12. 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

  13. Conditional self-discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats.

    Science.gov (United States)

    Penagos-Corzo, Julio C; Bonilla, Andrea; Rodríguez-Moreno, Antonio; Flores, Gonzalo; Negrete-Díaz, José V

    2015-11-01

    We studied conditional self-discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self-discrimination. For this purpose, we used thirty 10-week-old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self-discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi-Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self-discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self-discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes. © 2015 Wiley Periodicals, Inc.

  14. Emergence of realism: Enhanced visual artistry and high accuracy of visual numerosity representation after left prefrontal damage.

    Science.gov (United States)

    Takahata, Keisuke; Saito, Fumie; Muramatsu, Taro; Yamada, Makiko; Shirahase, Joichiro; Tabuchi, Hajime; Suhara, Tetsuya; Mimura, Masaru; Kato, Motoichiro

    2014-05-01

    Over the last two decades, evidence of enhancement of drawing and painting skills due to focal prefrontal damage has accumulated. It is of special interest that most artworks created by such patients were highly realistic ones, but the mechanism underlying this phenomenon remains to be understood. Our hypothesis is that enhanced tendency of realism was associated with accuracy of visual numerosity representation, which has been shown to be mediated predominantly by right parietal functions. Here, we report a case of left prefrontal stroke, where the patient showed enhancement of artistic skills of realistic painting after the onset of brain damage. We investigated cognitive, functional and esthetic characteristics of the patient׳s visual artistry and visual numerosity representation. Neuropsychological tests revealed impaired executive function after the stroke. Despite that, the patient׳s visual artistry related to realism was rather promoted across the onset of brain damage as demonstrated by blind evaluation of the paintings by professional art reviewers. On visual numerical cognition tasks, the patient showed higher performance in comparison with age-matched healthy controls. These results paralleled increased perfusion in the right parietal cortex including the precuneus and intraparietal sulcus. Our data provide new insight into mechanisms underlying change in artistic style due to focal prefrontal lesion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Childhood emotional maltreatment severity is associated with dorsal medial prefrontal cortex responsivity to social exclusion in young adults.

    Science.gov (United States)

    van Harmelen, Anne-Laura; Hauber, Kirsten; Gunther Moor, Bregtje; Spinhoven, Philip; Boon, Albert E; Crone, Eveline A; Elzinga, Bernet M

    2014-01-01

    Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.

  16. Positive symptoms and water diffusivity of the prefrontal and temporal cortices in schizophrenia patients: a pilot study.

    Science.gov (United States)

    Park, Jin Young; Park, Hae-Jeong; Kim, Dae-Jin; Kim, Jae-Jin

    2014-10-30

    The development of diffusion tensor imaging (DTI) has provided information about microstructural changes in the brain. Most DTI studies have focused on white matter (WM). Few DTI studies have examined the gray matter (GM) in schizophrenia and, to date, there has been no attempt to identify the relationship between water diffusivity and symptom severity in schizophrenia. The present study aimed to examine microstructural deficits in the dorsal prefrontal cortex (DPFC) and temporal cortex in schizophrenia patients using fractional anisotropy (FA) and water diffusivity. This study also explored the relationship between DTI measurements and psychotic symptoms. Magnetic resonance imaging (MRI) and DTI were used to study 19 schizophrenia patients and 19 healthy controls. Fractional anisotropy, axial diffusivity, radial diffusivity, and regional volumes were measured in the prefrontal cortex and temporal cortex. On DTI measurements, patients showed increased axial and radial diffusivities in the prefrontal cortex and temporal cortex, but they did not demonstrate any difference in fractional anisotropy and regional volumes. Additionally, axial and radial diffusivities were significantly correlated with positive symptom scores in all regions of interest. These results indicate that water diffusivity measurements, including axial and radial diffusivities, can be used to identify microstructural changes in the gray matter in schizophrenia that may be related to symptom severity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Test-retest reliability of the prefrontal response to affective pictures based on functional near-infrared spectroscopy

    Science.gov (United States)

    Huang, Yuxia; Mao, Mengchai; Zhang, Zong; Zhou, Hui; Zhao, Yang; Duan, Lian; Kreplin, Ute; Xiao, Xiang; Zhu, Chaozhe

    2017-01-01

    Functional near-infrared spectroscopy (fNIRS) is being increasingly applied to affective and social neuroscience research; however, the reliability of this method is still unclear. This study aimed to evaluate the test-retest reliability of the fNIRS-based prefrontal response to emotional stimuli. Twenty-six participants viewed unpleasant and neutral pictures, and were simultaneously scanned by fNIRS in two sessions three weeks apart. The reproducibility of the prefrontal activation map was evaluated at three spatial scales (mapwise, clusterwise, and channelwise) at both the group and individual levels. The influence of the time interval was also explored and comparisons were made between longer (intersession) and shorter (intrasession) time intervals. The reliabilities of the activation map at the group level for the mapwise (up to 0.88, the highest value appeared in the intersession assessment) and clusterwise scales (up to 0.91, the highest appeared in the intrasession assessment) were acceptable, indicating that fNIRS may be a reliable tool for emotion studies, especially for a group analysis and under larger spatial scales. However, it should be noted that the individual-level and the channelwise fNIRS prefrontal responses were not sufficiently stable. Future studies should investigate which factors influence reliability, as well as the validity of fNIRS used in emotion studies.

  18. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training.

    Science.gov (United States)

    Morena, Maria; Roozendaal, Benno; Trezza, Viviana; Ratano, Patrizia; Peloso, Andrea; Hauer, Daniela; Atsak, Piray; Trabace, Luigia; Cuomo, Vincenzo; McGaugh, James L; Schelling, Gustav; Campolongo, Patrizia

    2014-12-23

    Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation.

  19. Differential patterns of prefrontal MEG activation during verbal & visual encoding and retrieval.

    Directory of Open Access Journals (Sweden)

    Garreth Prendergast

    Full Text Available The spatiotemporal profile of activation of the prefrontal cortex in verbal and non-verbal recognition memory was examined using magnetoencephalography (MEG. Sixteen neurologically healthy right-handed participants were scanned whilst carrying out a modified version of the Doors and People Test of recognition memory. A pattern of significant prefrontal activity was found for non-verbal and verbal encoding and recognition. During the encoding, verbal stimuli activated an area in the left ventromedial prefrontal cortex, and non-verbal stimuli activated an area in the right. A region in the left dorsolateral prefrontal cortex also showed significant activation during the encoding of non-verbal stimuli. Both verbal and non-verbal stimuli significantly activated an area in the right dorsomedial prefrontal cortex and the right anterior prefrontal cortex during successful recognition, however these areas showed temporally distinct activation dependent on material, with non-verbal showing activation earlier than verbal stimuli. Additionally, non-verbal material activated an area in the left anterior prefrontal cortex during recognition. These findings suggest a material-specific laterality in the ventromedial prefrontal cortex during encoding for verbal and non-verbal but also support the HERA model for verbal material. The discovery of two process dependent areas during recognition that showed patterns of temporal activation dependent on material demonstrates the need for the application of more temporally sensitive techniques to the involvement of the prefrontal cortex in recognition memory.

  20. Differential patterns of prefrontal MEG activation during verbal & visual encoding and retrieval.

    Science.gov (United States)

    Prendergast, Garreth; Limbrick-Oldfield, Eve; Ingamells, Ed; Gathercole, Susan; Baddeley, Alan; Green, Gary G R

    2013-01-01

    The spatiotemporal profile of activation of the prefrontal cortex in verbal and non-verbal recognition memory was examined using magnetoencephalography (MEG). Sixteen neurologically healthy right-handed participants were scanned whilst carrying out a modified version of the Doors and People Test of recognition memory. A pattern of significant prefrontal activity was found for non-verbal and verbal encoding and recognition. During the encoding, verbal stimuli activated an area in the left ventromedial prefrontal cortex, and non-verbal stimuli activated an area in the right. A region in the left dorsolateral prefrontal cortex also showed significant activation during the encoding of non-verbal stimuli. Both verbal and non-verbal stimuli significantly activated an area in the right dorsomedial prefrontal cortex and the right anterior prefrontal cortex during successful recognition, however these areas showed temporally distinct activation dependent on material, with non-verbal showing activation earlier than verbal stimuli. Additionally, non-verbal material activated an area in the left anterior prefrontal cortex during recognition. These findings suggest a material-specific laterality in the ventromedial prefrontal cortex during encoding for verbal and non-verbal but also support the HERA model for verbal material. The discovery of two process dependent areas during recognition that showed patterns of temporal activation dependent on material demonstrates the need for the application of more temporally sensitive techniques to the involvement of the prefrontal cortex in recognition memory.

  1. Reward feedback stimuli elicit high-beta EEG oscillations in human dorsolateral prefrontal cortex.

    Science.gov (United States)

    HajiHosseini, Azadeh; Hosseini, Azadeh Haji; Holroyd, Clay B

    2015-08-17

    Reward-related feedback stimuli have been observed to elicit a burst of power in the beta frequency range over frontal areas of the human scalp. Recent discussions have suggested possible neural sources for this activity but there is a paucity of empirical evidence on the question. Here we recorded EEG from participants while they navigated a virtual T-maze to find monetary rewards. Consistent with previous studies, we found that the reward feedback stimuli elicited an increase in beta power (20-30 Hz) over a right-frontal area of the scalp. Source analysis indicated that this signal was produced in the right dorsolateral prefrontal cortex (DLPFC). These findings align with previous observations of reward-related beta oscillations in the DLPFC in non-human primates. We speculate that increased power in the beta frequency range following reward receipt reflects the activation of task-related neural assemblies that encode the stimulus-response mapping in working memory.

  2. Memory processes and prefrontal network dysfunction in cryptogenic epilepsy.

    Science.gov (United States)

    Vlooswijk, Marielle C G; Jansen, Jacobus F A; Jeukens, Cécile R L P N; Majoie, H J Marian; Hofman, Paul A M; de Krom, Marc C T F M; Aldenkamp, Albert P; Backes, Walter H

    2011-08-01

    Impaired memory performance is the most frequently reported cognitive problem in patients with chronic epilepsy. To examine memory deficits many studies have focused on the role of the mesiotemporal lobe, mostly with hippocampal abnormalities. However, the role of the prefrontal brain remains unresolved. To investigate the neuronal correlates of working memory dysfunction in patients without structural lesions, a combined study of neurocognitive assessment, hippocampal and cerebral volumetry, and functional magnetic resonance imaging of temporal and frontal memory networks was performed. Thirty-six patients with cryptogenic localization-related epilepsy and 21 healthy controls underwent neuropsychological assessment of intelligence (IQ) and memory. On T(1) -weighted images obtained by 3-Tesla magnetic resonance imaging (MRI), volumetry of the hippocampi and the cerebrum was performed. Functional MRI (fMRI) was performed with a novel picture encoding and Sternberg paradigm that activated different memory-mediating brain regions. Functional connectivity analysis comprised cross-correlation of signal time-series of the most strongly activated regions involved in working memory function. Patients with epilepsy displayed lower IQ values; impaired transient aspects of information processing, as indicated by lower scores on the digit-symbol substitution test (DSST); and decreased short-term memory performance relative to healthy controls, as measured with the Wechsler Adult Intelligence Scale subtests for working memory, and word and figure recognition. This could not be related to any hippocampal volume changes. No group differences were found regarding volumetry or fMRI-derived functional activation. In the Sternberg paradigm, a network involving the anterior cingulate and the middle and inferior frontal gyrus was activated. A reduced strength of four connections in this prefrontal network was associated with the DSST and word recognition performance in the patient

  3. Precuneus-prefrontal activity during awareness of visual verbal stimuli

    DEFF Research Database (Denmark)

    Kjaer, T W; Nowak, M; Kjær, Klaus Wilbrandt

    2001-01-01

    Awareness is a personal experience, which is only accessible to the rest of world through interpretation. We set out to identify a neural correlate of visual awareness, using brief subliminal and supraliminal verbal stimuli while measuring cerebral blood flow distribution with H(2)(15)O PET....... Awareness of visual verbal stimuli differentially activated medial parietal association cortex (precuneus), which is a polymodal sensory cortex, and dorsolateral prefrontal cortex, which is thought to be primarily executive. Our results suggest participation of these higher order perceptual and executive...

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

    Science.gov (United States)

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

    2016-02-01

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

  5. Hypofunction of prefrontal cortex NMDA receptors does not change stress-induced release of dopamine and noradrenaline in amygdala but disrupts aversive memory.

    Science.gov (United States)

    Del Arco, Alberto; Ronzoni, Giacomo; Mora, Francisco

    2015-07-01

    A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia. The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event. Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory. Acute stress increased amygdala dialysate concentrations of dopamine (160% of baseline), noradrenaline (145% of baseline) and corticosterone (170% of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test. These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.

  6. Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia.

    Science.gov (United States)

    Santini, Martin A; Ratner, Cecilia; Aznar, Susana; Klein, Anders B; Knudsen, Gitte M; Mikkelsen, Jens D

    2013-05-01

    Prefrontal serotonin 2A receptors (5-HT2A Rs) have been linked to the pathogenesis and treatment of schizophrenia. Many antipsychotics fully occupy 5-HT2A R at clinical relevant doses, and activation of 5-HT2A receptors by lysergic acid diethylamide (LSD) and LSD-like drugs induces a schizophrenia-like psychosis in humans. Subchronic phencyclidine (PCP) administration is a well-established model for schizophrenia-like symptoms in rodents. The aim of the present study was to investigate whether subchronic PCP administration changes expression, binding, or functionality of cortical 5-HT2A Rs. As a measure of 5-HT2A R functionality, we used the 5-HT2A R agonist 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch response (HTR) and mRNA expression of the immediate-early genes (IEGs) activity-related cytoskeletal associated-protein (Arc), c-fos, and early growth response protein 2 (egr-2) in the frontal cortex. Mice were treated with PCP (10 mg/kg) or saline for 10 days, followed by a 5-day washout period. The PCP pretreatment increased the overall induction of HTR and frontal cortex IEG mRNA expression following a single challenge with DOI. These functional changes were not associated with changes in 5-HT2A R binding. Also, binding of the 5-HT1A R and the 5-HT transporter was unaffected. Finally, basal mRNA level of Arc was increased in the prefrontal cortex after subchronic PCP administration as revealed with in situ hybridization. Together these findings indicate that PCP administration produces changes in the brain that result in an increase in the absolute effect of DOI. Therefore, neurotransmission involving the 5-HT2A R could contribute to the behavioral deficits observed after PCP treatment. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

  7. Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

    Science.gov (United States)

    Jiménez-Sánchez, Laura; Linge, Raquel; Campa, Leticia; Valdizán, Elsa M; Pazos, Ángel; Díaz, Álvaro; Adell, Albert

    2016-09-01

    Deep brain stimulation (DBS) is a treatment that has shown some efficacy in treatment-resistant depression. In particular, DBS of the subcallosal cingulate gyrus (Brodmann's area 25, Cg25) has been successfully applied to treat refractory depression. In the rat, we have demonstrated that DBS applied to infralimbic (IL) cortex elevates the levels of glutamate and monoamines in the prefrontal cortex, and requires the stimulation of cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors for its antidepressant-like effects. However, the molecular targets of IL DBS are not fully known. To gain insight into these pathways, we have investigated whether IL DBS is able to reverse the behavioral, biochemical and molecular changes exhibited by the olfactory bulbectomized (OBX) rat. Our results revealed that 1 h IL DBS diminished hyperlocomotion, hyperemotionality and anhedonia, and increased social interaction shown by the OBX rats. Further, IL DBS increased prefrontal efflux of glutamate and serotonin in both sham-operated and OBX rats. With regard to molecular targets, IL DBS increases the synthesis of brain-derived neurotrophic factor (BDNF) and the GluA1 AMPA receptor subunit, and stimulates the Akt/mammalian target of rapamycin (mTOR) as well as the AMPA receptor/c-AMP response element binding (CREB) pathways. Temsirolimus, a known in vivo mTOR blocker, suppressed the antidepressant-like effect of IL DBS in naïve rats in the forced swim test, thus demonstrating for the first time that mTOR signaling is required for the antidepressant-like effects of IL DBS, which is in line with the antidepressant response of other rapid-acting antidepressant drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Prefrontal gyrification in psychotic bipolar I disorder vs. schizophrenia.

    Science.gov (United States)

    Nenadic, Igor; Maitra, Raka; Dietzek, Maren; Langbein, Kerstin; Smesny, Stefan; Sauer, Heinrich; Gaser, Christian

    2015-10-01

    Bipolar disorder and schizophrenia share phenotypic and genotypic features, but might differ in aspects of abnormal neurodevelopmental trajectories. We studied gyrification, a marker of early developmental pathology, in high-resolution MRI scans of 34 patients with schizophrenia, 17 euthymic bipolar I disorder patients with previous psychotic symptoms, and 34 matched healthy controls in order to test the hypothesis of overlapping and diverging prefrontal gyrification abnormalities. We applied a novel, validated method for measuring local gyrification in each vertex point of the reconstructed cortical surface. Psychotic bipolar I patients had higher gyrification in dorsal anterior and infragenual cingulate cortex compared to either schizophrenia or healthy controls, while schizophrenia patients had higher gyrification than controls in anterior medial (BA 10) and orbitofrontal areas, altogether indicating disease-specific alterations in the prefrontal cortex. Our findings indicate gyrification changes in a specific subgroup of bipolar I disorder to affect an area relevant to emotion regulation, and distinct from changes seen in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 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.

  10. Electrophysiological Mapping of Novel Prefrontal – Cerebellar Pathways

    Science.gov (United States)

    Watson, Thomas C.; Jones, Matthew W.; Apps, Richard

    2009-01-01

    Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non-motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL) and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35 ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre); they were not attenuated by local anaesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency (approximately 30 ms). Single unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s) of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions. PMID:19738932

  11. Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia.

    Science.gov (United States)

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

    2004-01-01

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

  12. Reality monitoring impairment in schizophrenia reflects specific prefrontal cortex dysfunction.

    Science.gov (United States)

    Garrison, Jane R; Fernandez-Egea, Emilio; Zaman, Rashid; Agius, Mark; Simons, Jon S

    2017-01-01

    Reality monitoring impairment is often reported in schizophrenia but the neural basis of this deficit is poorly understood. Difficulties with reality monitoring could be attributable to the same pattern of neural dysfunction as other cognitive deficits that characterize schizophrenia, or might instead represent a separable and dissociable impairment. This question was addressed through direct comparison of behavioral performance and neural activity associated with reality monitoring and working memory in patients with schizophrenia and matched healthy controls. Participants performed a word-pair reality monitoring task and a Sternberg working memory task while undergoing fMRI scanning. Distinct behavioral deficits were observed in the patients during performance of each task, which were associated with separable task- and region-specific dysfunction in the medial anterior prefrontal cortex for reality monitoring and dorsolateral prefrontal cortex for working memory. The results suggest that reality monitoring impairment is a distinct neurocognitive deficit in schizophrenia. The findings are consistent with the presence of a range of dissociable cognitive deficits in schizophrenia which may be associated with variable functional and structural dysconnectivity in underlying processing networks.

  13. Reality monitoring impairment in schizophrenia reflects specific prefrontal cortex dysfunction

    Directory of Open Access Journals (Sweden)

    Jane R. Garrison

    2017-01-01

    Full Text Available Reality monitoring impairment is often reported in schizophrenia but the neural basis of this deficit is poorly understood. Difficulties with reality monitoring could be attributable to the same pattern of neural dysfunction as other cognitive deficits that characterize schizophrenia, or might instead represent a separable and dissociable impairment. This question was addressed through direct comparison of behavioral performance and neural activity associated with reality monitoring and working memory in patients with schizophrenia and matched healthy controls. Participants performed a word-pair reality monitoring task and a Sternberg working memory task while undergoing fMRI scanning. Distinct behavioral deficits were observed in the patients during performance of each task, which were associated with separable task- and region-specific dysfunction in the medial anterior prefrontal cortex for reality monitoring and dorsolateral prefrontal cortex for working memory. The results suggest that reality monitoring impairment is a distinct neurocognitive deficit in schizophrenia. The findings are consistent with the presence of a range of dissociable cognitive deficits in schizophrenia which may be associated with variable functional and structural dysconnectivity in underlying processing networks.

  14. Prefrontal /accumbal catecholamine system processes high motivational salience.

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    Stefano ePuglisi-Allegra

    2012-06-01

    Full Text Available Motivational salience regulates the strength of goal seeking, the amount of risk taken, and the energy invested from mild to extreme. Highly motivational experiences promote highly persistent memories. Although this phenomenon is adaptive in normal conditions, experiences with extremely high levels of motivational salience can promote development of memories that can be re-experienced intrusively for long time resulting in maladaptive outcomes.Neural mechanisms mediating motivational salience attribution are, therefore, very important for individual and species survival and for well-being. However, these neural mechanisms could be implicated in attribution of abnormal motivational salience to different stimuli leading to maladaptive compulsive seeking or avoidance. We have offered the first evidence that prefrontal cortical norepinephrine transmission is a necessary condition for motivational salience attribution to highly salient stimuli, through modulation of dopamine in the nucleus accumbens, a brain area involved in all motivated behaviors. Moreover, we have shown that prefrontal-accumbal catecholamine system determines approach or avoidance responses to both reward- and aversion-related stimuli only when the salience of the unconditioned stimulus is high enough to induce sustained catecholamine activation, thus affirming that this system processes motivational salience attribution selectively to highly salient events.

  15. Disturbed prefrontal and temporal brain function during emotion and cognition interaction in criminal psychopathy.

    Science.gov (United States)

    Müller, Jürgen L; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

    2008-01-01

    Impaired emotional responsiveness has been revealed as a hallmark of psychopathy. In spite of an increasing database on emotion processing, studies on cognitive function and in particular on the impact of emotion on cognition in psychopathy are rare. We used pictures from the International Affective Picture Set (IAPS) and a Simon Paradigm to address emotion-cognition interaction while functional and structural imaging data were obtained in 12 healthy controls and 10 psychopaths. We found an impaired emotion-cognition interaction in psychopaths that correlated with a changed prefrontal and temporal brain activation. With regard to the temporal cortex, it is shown that structure and function of the right superior temporal gyrus is disturbed in psychopathy, supporting a neurobiological approach to psychopathy, in which structure and function of the right STG may be important. (c) 2008 John Wiley & Sons, Ltd.

  16. Role of the prefrontal cortex in the control of express saccades. A transcranial magnetic stimulation study.

    Science.gov (United States)

    Müri, R M; Rivaud, S; Gaymard, B; Ploner, C J; Vermersch, A I; Hess, C W; Pierrot-Deseilligny, C

    1999-02-01

    Single pulse transcranial magnet stimulation (TMS) was applied in five subjects during a saccadic gap task, i.e. with a temporal gap of 200 ms between the extinguishing of the central fixation point and the appearance of the lateral target. In all subjects, a significant increase of contralateral express saccades was found when TMS was applied over the dorsolateral prefrontal cortex (DPFC) at the end of the gap of 200 ms. Earlier stimulation over the DPFC during the gap had no significant effect. Furthermore, stimulation over the posterior parietal cortex with the same time intervals, and stimulation during a no gap task had no significant influence on express saccades. These results suggest that TMS is capable of interfering specifically with the functioning of the DPFC, probably by inhibition of this region. Possibly such stimulation of the DPFC reduces the inhibition by this region onto the superior colliculus, which results in a facilitation of express saccades.

  17. Mental calculation in a prodigy is sustained by right prefrontal and medial temporal areas.

    Science.gov (United States)

    Pesenti, M; Zago, L; Crivello, F; Mellet, E; Samson, D; Duroux, B; Seron, X; Mazoyer, B; Tzourio-Mazoyer, N

    2001-01-01

    Calculating prodigies are individuals who are exceptional at quickly and accurately solving complex mental calculations. With positron emission tomography (PET), we investigated the neural bases of the cognitive abilities of an expert calculator and a group of non-experts, contrasting complex mental calculation to memory retrieval of arithmetic facts. We demonstrated that calculation expertise was not due to increased activity of processes that exist in non-experts; rather, the expert and the non-experts used different brain areas for calculation. We found that the expert could switch between short-term effort-requiring storage strategies and highly efficient episodic memory encoding and retrieval, a process that was sustained by right prefrontal and medial temporal areas.

  18. Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment.

    Science.gov (United States)

    Burgos-Robles, Anthony; Kimchi, Eyal Y; Izadmehr, Ehsan M; Porzenheim, Mary Jane; Ramos-Guasp, William A; Nieh, Edward H; Felix-Ortiz, Ada C; Namburi, Praneeth; Leppla, Christopher A; Presbrey, Kara N; Anandalingam, Kavitha K; Pagan-Rivera, Pablo A; Anahtar, Melodi; Beyeler, Anna; Tye, Kay M

    2017-06-01

    Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.

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

    Directory of Open Access Journals (Sweden)

    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

  20. Downregulation of GNA13-ERK network in prefrontal cortex of schizophrenia brain identified by combined focused and targeted quantitative proteomics.

    Science.gov (United States)

    Hirayama-Kurogi, Mio; Takizawa, Yohei; Kunii, Yasuto; Matsumoto, Junya; Wada, Akira; Hino, Mizuki; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Kondo, Takeshi; Ito, Shingo; Tachikawa, Masanori; Niwa, Shin-Ichi; Yabe, Hirooki; Terasaki, Tetsuya; Setou, Mitsutoshi; Ohtsuki, Sumio

    2017-03-31

    Schizophrenia is a disabling mental illness associated with dysfunction of the prefrontal cortex, which affects cognition and emotion. The purpose of the present study was to identify altered molecular networks in the prefrontal cortex of schizophrenia patients by comparing protein expression levels in autopsied brains of patients and controls, using a combination of targeted and focused quantitative proteomics. We selected 125 molecules possibly related to schizophrenia for quantification by knowledge-based targeted proteomics. Among the quantified molecules, GRIK4 and MAO-B were significantly decreased in plasma membrane and cytosolic fractions, respectively, of prefrontal cortex. Focused quantitative proteomics identified 15 increased and 39 decreased proteins. Network analysis identified "GNA13-ERK1-eIF4G2 signaling" as a downregulated network, and proteins involved in this network were significantly decreased. Furthermore, searching downstream of eIF4G2 revealed that eIF4A1/2 and CYFIP1 were decreased, suggesting that downregulation of the network suppresses expression of CYFIP1, which regulates actin remodeling and is involved in axon outgrowth and spine formation. Downregulation of this signaling seems likely to impair axon formation and synapse plasticity of neuronal cells, and could be associated with development of cognitive impairment in the pathology of schizophrenia. The present study compared the proteome of the prefrontal cortex between schizophrenia patients and healthy controls by means of targeted proteomics and global quantitative proteomics. Targeted proteomics revealed that GRIK4 and MAOB were significantly decreased among 125 putatively schizophrenia-related proteins in prefrontal cortex of schizophrenia patients. Global quantitative proteomics identified 54 differentially expressed proteins in schizophrenia brains. The protein profile indicates attenuation of "GNA13-ERK signaling" in schizophrenia brain. In particular, EIF4G2 and CYFIP1

  1. Activation of the prefrontal cortex by unilateral transcranial direct current stimulation leads to an asymmetrical effect on risk preference in frames of gain and loss.

    Science.gov (United States)

    Ye, Hang; Huang, Daqiang; Wang, Siqi; Zheng, Haoli; Luo, Jun; Chen, Shu

    2016-10-01

    Previous brain imaging and brain stimulation studies have suggested that the dorsolateral prefrontal cortex may be critical in regulating risk-taking behavior, although its specific causal effect on people's risk preference remains controversial. This paper studied the independent modulation of the activity of the right and left dorsolateral prefrontal cortex using various configurations of transcranial direct current stimulation. We designed a risk-measurement table and adopted a within-subject design to compare the same participant's risk preference before and after unilateral stimulation when presented with different frames of gain and loss. The results confirmed a hemispheric asymmetry and indicated that the right dorsolateral prefrontal cortex has an asymmetric effect on risk preference regarding frames of gain and loss. Enhancing the activity of the right dorsolateral prefrontal cortex significantly decreased the participants' degree of risk aversion in the gain frame, whereas it increased the participants' degree of risk aversion in the loss frame. Our findings provide important information regarding the impact of transcranial direct current stimulation on the risk preference of healthy participants. The effects observed in our experiment compared with those of previous studies provide further evidence of the effects of hemispheric and frame-dependent asymmetry. These findings may be helpful in understanding the neural basis of risk preference in humans, especially when faced with decisions involving possible gain or loss relative to the status quo. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Is the prefrontal cortex especially enlarged in the human brain allometric relations and remapping factors.

    Science.gov (United States)

    Passingham, Richard E; Smaers, Jeroen B

    2014-01-01

    There has been no agreement as to whether the prefrontal cortex is especially enlarged in the human brain. To answer this question, we analyzed the only two datasets that provide information on total prefrontal cortex volume based on cytoarchitectonic criteria. One delineated the prefrontal cortex proper on the basis of cytoarchitectonic criteria; the other used a proxy of the prefrontal cortex based on a cytoarchitectonic delineation of the frontal lobe. To investigate whether all cortical association areas, including the prefrontal cortex, are enlarged in the human brain, we scaled the different areas to a common reference, the primary visual cortex. To investigate whether the prefrontal cortex is more enlarged than other association areas, we scaled it relative to its inputs from and outputs to other nonprimary areas. We carried out separate regression analyses using different data samples as a predictive baseline group: data for monkeys alone informs us on whether great apes are different from monkeys; data for all non-human anthropoids, including great apes, informs us on whether humans are different from all other primates. The analyses show that the value for the human prefrontal cortex is greater than expected, and that this is true even when data for the great apes are included in the analysis. They also show that the chimpanzee prefrontal cortex is greater than expected for a monkey with a similar sized cortex. We discuss possible functional consequences.

  3. 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

  4. 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…

  5. Developmental Differences in Prefrontal Activation during Working Memory Maintenance and Manipulation for Different Memory Loads

    Science.gov (United States)

    Jolles, Dietsje D.; Kleibeuker, Sietske W.; Rombouts, Serge A. R. B.; Crone, Eveline A.

    2011-01-01

    The ability to keep information active in working memory is one of the cornerstones of cognitive development. Prior studies have demonstrated that regions which are important for working memory performance in adults, such as dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and superior parietal cortex, become…

  6. Close Interrelation of Motor Development and Cognitive Development and of the Cerebellum and Prefrontal Cortex.

    Science.gov (United States)

    Diamond, Adele

    2000-01-01

    Argues that motor and cognitive development may be fundamentally interrelated. Summarizes evidence of close co-activation of the neocerebellum and dorsolateral prefrontal cortex in functional neuroimaging, similarities in the cognitive sequelae of damage to dorsolateral prefrontal cortex and the neocerebellum, motor deficits in…

  7. Decreased expression of vesicular glutamate transporter 1 and complexin II mRNAs in schizophrenia: further evidence for a synaptic pathology affecting glutamate neurons.

    Science.gov (United States)

    Eastwood, S L; Harrison, P J

    2005-03-01

    Synaptic protein gene expression is altered in schizophrenia. In the hippocampal formation there may be particular involvement of glutamatergic neurons and their synapses, but overall the profile remains unclear. In this in situ hybridization histochemistry (ISHH) study, we examined four informative synaptic protein transcripts: vesicular glutamate transporter (VGLUT) 1, VGLUT2, complexin I, and complexin II, in dorsolateral prefrontal cortex (DPFC), superior temporal cortex (STC), and hippocampal formation, in 13 subjects with schizophrenia and 18 controls. In these areas, VGLUT1 and complexin II are expressed primarily by excitatory neurons, whereas complexin I is mainly expressed by inhibitory neurons. In schizophrenia, VGLUT1 mRNA was decreased in hippocampal formation and DPFC, complexin II mRNA was reduced in DPFC and STC, and complexin I mRNA decreased in STC. Hippocampal VGLUT1 mRNA declined with age selectively in the schizophrenia group. VGLUT2 mRNA was not quantifiable due to its low level. The data provide additional evidence for a synaptic pathology in schizophrenia, in terms of a reduced expression of three synaptic protein genes. In the hippocampus, the loss of VGLUT1 mRNA supports data indicating that glutamatergic presynaptic deficits are prominent, whereas the pattern of results in temporal and frontal cortex suggests broadly similar changes may affect inhibitory and excitatory neurons. The impairment of synaptic transmission implied by the synaptic protein reductions may contribute to the dysfunction of cortical neural circuits that characterises the disorder.

  8. 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

  9. 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.

  10. 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.

  11. Gene expression in the prefrontal cortex during adolescence: implications for the onset of schizophrenia

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    Weickert Cynthia

    2009-05-01

    Full Text Available Abstract Background Many critical maturational processes take place in the human brain during postnatal development. In particular, the prefrontal cortex does not reach maturation until late adolescence and this stage is associated with substantial white matter volume increases. Patients with schizophrenia and other major psychiatric disorders tend to first present with overt symptoms during late adolescence/early adulthood and it has been proposed that this developmental stage represents a "window of vulnerability". Methods In this study we used whole genome microarrays to measure gene expression in post mortem prefrontal cortex tissue from human individuals ranging in age from 0 to 49 years. To identify genes specifically altered in the late adolescent period, we applied a template matching procedure. Genes were identified which showed a significant correlation to a template showing a peak of expression between ages 15 and 25. Results Approximately 2000 genes displayed an expression pattern that was significantly correlated (positively or negatively with the template. In the majority of cases, these genes in fact reached a plateau during adolescence with only subtle changes thereafter. These include a number of genes previously associated with schizophrenia including the susceptibility gene neuregulin 1 (NRG1. Functional profiling revealed peak expression in late adolescence for genes associated with energy metabolism and protein and lipid synthesis, together with decreases for genes involved in glutamate and neuropeptide signalling and neuronal development/plasticity. Strikingly, eight myelin-related genes previously found decreased in schizophrenia brain tissue showed a peak in their expression levels in late adolescence, while the single myelin gene reported increased in patients with schizophrenia was decreased in late adolescence. Conclusion The observed changes imply that molecular mechanisms critical for adolescent brain development are

  12. Harming kin to save strangers: further evidence for abnormally utilitarian moral judgments after ventromedial prefrontal damage.

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    Thomas, Bradley C; Croft, Katie E; Tranel, Daniel

    2011-09-01

    The ventromedial PFC (vmPFC) has been implicated as a critical neural substrate mediating the influence of emotion on moral reasoning. It has been shown that the vmPFC is especially important for making moral judgments about "high-conflict" moral dilemmas involving direct personal actions, that is, scenarios that pit compelling utilitarian considerations of aggregate welfare against the highly emotionally aversive act of directly causing harm to others [Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., et al. Damage to the prefrontal cortex increases utilitarian moral judgments. Nature, 446, 908-911, 2007]. The current study was designed to elucidate further the role of the vmPFC in high-conflict moral judgments, including those that involve indirect personal actions, such as indirectly causing harm to one's kin to save a group of strangers. We found that patients with vmPFC lesions were more likely than brain-damaged and healthy comparison participants to endorse utilitarian outcomes on high-conflict dilemmas regardless of whether the dilemmas (1) entailed direct versus indirect personal harms and (2) were presented from the Self versus Other perspective. In addition, all groups were more likely to endorse utilitarian outcomes in the Other perspective as compared with the Self perspective. These results provide important extensions of previous work, and the findings align with the proposal that the vmPFC is critical for reasoning about moral dilemmas in which anticipating the social-emotional consequences of an action (e.g., guilt or remorse) is crucial for normal moral judgments [Greene, J. D. Why are VMPFC patients more utilitarian?: A dual-process theory of moral judgment explains. Trends in Cognitive Sciences, 11, 322-323, 2007; Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., et al. Damage to the prefrontal cortex increases utilitarian moral judgments. Nature, 446, 908-911, 2007].

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

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    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

  14. Disruption of medial prefrontal synchrony in the subchronic phencyclidine model of schizophrenia in rats.

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    Young, A M J; Stubbendorff, C; Valencia, M; Gerdjikov, T V

    2015-02-26

    Subchronic treatment with the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP) produces behavioral abnormalities in rodents which are considered a reliable pharmacological model of neurocognitive deficits in schizophrenia. Alterations in prefrontal neuronal firing after acute PCP administration have been observed, however enduring changes in prefrontal activity after subchronic PCP treatment have not been studied. To address this we have recorded cortical oscillations and unit responses in putative cortical pyramidal cells in subchronic PCP-treated rats (2mg/kg twice daily for 7 days) under urethane anesthesia. We found that this regimen reduced theta oscillations in the medial prefrontal cortex. It further produced abnormal cortical synchronization in putative cortical pyramidal cells. These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks. Copyright © 2015. Published by Elsevier Ltd.

  15. Behavioral effects of chronically elevated corticosterone in subregions of the medial prefrontal cortex.

    Science.gov (United States)

    Croteau, Joshua D; Schulkin, Jay; Shepard, Jack D

    2017-01-01

    The medial prefrontal cortex is a key mediator of behavioral aspects of the defense response. Since chronic exposure to elevated glucocorticoids alters the dendritic structure of neurons in the medial prefrontal cortex, such exposure may alter behavioral responses to danger as well. We examined the effects of chronically elevated corticosterone in discrete regions of the medial prefrontal cortex on exploration of the elevated plus-maze. Chronically elevated corticosterone in the prelimbic or infralimbic cortices reduced open arm exploration. This effect was specific to the ventral regions of the medial prefrontal cortex as corticosterone had no effect on plus-maze exploration when administered into the anterior cingulate cortex. Taken together, these findings demonstrate clear regional differences for the effects of corticosterone in the medial prefrontal cortex. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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

    2005-11-07

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

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

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    Annie Wai Yiu Chan

    2013-07-01

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

  18. Fast Left Prefrontal rTMS Acutely Suppresses Analgesic Effects of Perceived Controllability on the Emotional Component of Pain Experience

    OpenAIRE

    Borckardt, Jeffrey J.; Reeves, Scott T.; Frohman, Heather; Madan, Alok; Jensen, Mark P.; Patterson, David; Barth, Kelly; Smith, A. Richard; Gracely, Richard; George, Mark S.

    2010-01-01

    The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of ‘perceived controllability’ regarding pain, stress and learned helplessness. While the left dorsolateral prefrontal cortex is a common TMS target for treating clinical depression as well as...

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

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

    2018-02-15

    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

  20. Enhanced operant extinction and prefrontal excitability in a mouse model of Angelman syndrome.

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

    2018-02-05

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

  1. Distribution of Alox15 in the Rat Brain and Its Role in Prefrontal Cortical Resolvin D1 Formation and Spatial Working Memory.

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    Shalini, Suku-Maran; Ho, Christabel Fung-Yih; Ng, Yee-Kong; Tong, Jie-Xin; Ong, Eng-Shi; Herr, Deron R; Dawe, Gavin S; Ong, Wei-Yi

    2017-02-08

    Docosahexaenoic acid (DHA) is enriched in membrane phospholipids of the central nervous system (CNS) and has a role in aging and neuropsychiatric disorders. DHA is metabolized by the enzyme Alox15 to 17S-hydroxy-DHA, which is then converted to 7S-hydroperoxy,17S-hydroxy-DHA by a 5-lipoxygenase, and thence via epoxy intermediates to the anti-inflammatory molecule, resolvin D1 (RvD1 or 7S,8R,17S-trihydroxy-docosa-Z,9E,11E,13Z,15E,19Z-hexaenoic acid). In this study, we investigated the distribution and function of Alox15 in the CNS. RT-PCR of the CNS showed that the prefrontal cortex exhibits the highest Alox15 mRNA expression level, followed by the parietal association cortex and secondary auditory cortex, olfactory bulb, motor and somatosensory cortices, and the hippocampus. Western blot analysis was consistent with RT-PCR data, in that the prefrontal cortex, cerebral cortex, hippocampus, and olfactory bulb had high Alox15 protein expression. Immunohistochemistry showed moderate staining in the olfactory bulb, cerebral cortex, septum, striatum, cerebellar cortex, cochlear nuclei, spinal trigeminal nucleus, and dorsal horn of the spinal cord. Immuno-electron microscopy showed localization of Alox15 in dendrites, in the prefrontal cortex. Liquid chromatography mass spectrometry analysis showed significant decrease in resolvin D1 levels in the prefrontal cortex after inhibition or antisense knockdown of Alox15. Alox15 inhibition or antisense knockdown in the prefrontal cortex also blocked long-term potentiation of the hippocampo-prefrontal cortex pathway and increased errors in alternation, in the T-maze test. They indicate that Alox15 processing of DHA contributes to production of resolvin D1 and LTP at hippocampo-prefrontal cortical synapses and associated spatial working memory performance. Together, results provide evidence for a key role of anti-inflammatory molecules generated by Alox15 and DHA, such as resolvin D1, in memory. They suggest that neuroinflammatory

  2. Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.

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    Huiran Zhang

    Full Text Available OBJECTIVE: The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. METHOD: Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14 and a low suicide risk group (N = 19. A comparison group of healthy controls (N = 15 were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. RESULTS: Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. CONCLUSIONS: The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt.

  3. Interaction between Perceived Action and Music Sequences in the Left Prefrontal Area.

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    Wakita, Masumi

    2016-01-01

    Observing another person's piano play and listening to a melody interact with the observer's execution of piano play. This interaction is thought to occur because the execution of musical-action and the perception of both musical-action and musical-sound share a common representation in which the frontoparietal network is involved. However, it is unclear whether the perceptions of observed piano play and listened musical sound use a common neural resource. The present study used near-infrared spectroscopy to determine whether the interaction between the perception of musical-action and musical-sound sequences appear in the left prefrontal area. Measurements were obtained while participants watched videos that featured hands playing familiar melodies on a piano keyboard. Hand movements were paired with either a congruent or an incongruent melody. Two groups of participants (nine well-trained and nine less-trained) were instructed to identify the melody according to hand movements and to ignore the accompanying auditory track. Increased cortical activation was detected in the well-trained participants when hand movements were paired with incongruent melodies. Therefore, an interference effect was detected regarding the processing of action and sound sequences, indicating that musical-action sequences may be perceived with a representation that is also used for the perception of musical-sound sequences. However, in less-trained participants, such a contrast was not detected between conditions despite both groups featuring comparable key-touch reading abilities. Therefore, the current results imply that the left prefrontal area is involved in translating temporally structured sequences between domains. Additionally, expertise may be a crucial factor underlying this translation.

  4. Motor learning and modulation of prefrontal cortex: an fNIRS assessment

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    Ono, Yumie; Noah, Jack Adam; Zhang, Xian; Nomoto, Yasunori; Suzuki, Tatsuya; Shimada, Sotaro; Tachibana, Atsumichi; Bronner, Shaw; Hirsch, Joy

    2015-12-01

    Objective. Prefrontal hemodynamic responses are observed during performance of motor tasks. Using a dance video game (DVG), a complex motor task that requires temporally accurate footsteps with given visual and auditory cues, we investigated whether 20 h of DVG training modified hemodynamic responses of the prefrontal cortex in six healthy young adults. Approach. Fronto-temporal activity during actual DVG play was measured using functional near-infrared spectroscopy (fNIRS) pre- and post-training. To evaluate the training-induced changes in the time-courses of fNIRS signals, we employed a regression analysis using the task-specific template fNIRS signals that were generated from alternate well-trained and/or novice DVG players. The HRF was also separately incorporated as a template to construct an alternate regression model. Change in coefficients for template functions at pre- and post- training were determined and compared among different models. Main results. Training significantly increased the motor performance using the number of temporally accurate steps in the DVG as criteria. The mean oxygenated hemoglobin (ΔoxyHb) waveform changed from an activation above baseline pattern to that of a below baseline pattern. Participants showed significantly decreased coefficients for regressors of the ΔoxyHb response of novice players and HRF. The model using ΔoxyHb responses from both well-trained and novice players of DVG as templates showed the best fit for the ΔoxyHb responses of the participants at both pre- and post-training when analyzed with Akaike information criteria. Significance. These results suggest that the coefficients for the template ΔoxyHb responses of the novice players are sensitive indicators of motor learning during the initial stage of training and thus clinically useful to determine the improvement in motor performance when patients are engaged in a specific rehabilitation program.

  5. Reduction of Dual-task Costs by Noninvasive Modulation of Prefrontal Activity in Healthy Elders.

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    Manor, Brad; Zhou, Junhong; Jor'dan, Azizah; Zhang, Jue; Fang, Jing; Pascual-Leone, Alvaro

    2016-02-01

    Dual tasking (e.g., walking or standing while performing a cognitive task) disrupts performance in one or both tasks, and such dual-task costs increase with aging into senescence. Dual tasking activates a network of brain regions including pFC. We therefore hypothesized that facilitation of prefrontal cortical activity via transcranial direct current stimulation (tDCS) would reduce dual-task costs in older adults. Thirty-seven healthy older adults completed two visits during which dual tasking was assessed before and after 20 min of real or sham tDCS targeting the left pFC. Trials of single-task standing, walking, and verbalized serial subtractions were completed, along with dual-task trials of standing or walking while performing serial subtractions. Dual-task costs were calculated as the percent change in markers of gait and postural control and serial subtraction performance, from single to dual tasking. Significant dual-task costs to standing, walking, and serial subtraction performance were observed before tDCS (p < .01). These dual-task costs were less after real tDCS as compared with sham tDCS as well as compared with either pre-tDCS condition (p < .03). Further analyses indicated that tDCS did not alter single task performance but instead improved performance solely within dual-task conditions (p < .02). These results demonstrate that dual tasking can be improved by modulating prefrontal activity, thus indicating that dual-task decrements are modifiable and may not necessarily reflect an obligatory consequence of aging. Moreover, tDCS may ultimately serve as a novel approach to preserving dual-task capacity into senescence.

  6. Prefrontal, posterior parietal and sensorimotor network activity underlying speed control during walking

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    Thomas C Bulea

    2015-05-01

    Full Text Available Accumulating evidence suggests cortical circuits may contribute to control of human locomotion. Here, noninvasive electroencephalography (EEG recorded from able-bodied volunteers during a novel treadmill walking paradigm was used to assess neural correlates of walking. A systematic processing method, including a recently developed subspace reconstruction algorithm, reduced movement-related EEG artifact prior to independent component analysis and dipole source localization. We quantified cortical activity while participants tracked slow and fast target speeds across two treadmill conditions: an active mode that adjusted belt speed based on user movements and a passive mode reflecting a typical treadmill. Our results reveal frequency specific, multi-focal task related changes in cortical oscillations elicited by active walking. Low γ band power, localized to the prefrontal and posterior parietal cortices, was significantly increased during double support and early swing phases, critical points in the gait cycle since the active controller adjusted speed based on pelvis position and swing foot velocity. These phasic γ band synchronizations provide evidence that prefrontal and posterior parietal networks, previously implicated in visuo-spatial and somotosensory integration, are engaged to enhance lower limb control during gait. Sustained μ and β band desynchronization within sensorimotor cortex, a neural correlate for movement, was observed during walking thereby validating our methods for isolating cortical activity. Our results also demonstrate the utility of EEG recorded during locomotion for probing the multi-regional cortical networks which underpin its execution. For example, the cortical network engagement elicited by the active treadmill suggests that it may enhance neuroplasticity for more effective motor training.

  7. Reduced prefrontal activation in pediatric patients with obsessive-compulsive disorder during verbal episodic memory encoding.

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    Batistuzzo, Marcelo Camargo; Balardin, Joana Bisol; Martin, Maria da Graça Morais; Hoexter, Marcelo Queiroz; Bernardes, Elisa Teixeira; Borcato, Sonia; Souza, Marina de Marco E; Querido, Cicero Nardini; Morais, Rosa Magaly; de Alvarenga, Pedro Gomes; Lopes, Antonio Carlos; Shavitt, Roseli Gedanke; Savage, Cary R; Amaro, Edson; Miguel, Euripedes C; Polanczyk, Guilherme V; Miotto, Eliane C

    2015-10-01

    Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. The semantic clustering strategy score (SCS) predicted VEM performance in HC (p OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Local pharmacological manipulations of prefrontal dopamine affect conflict behaviour in rats.

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    Broersen, L.M.; Heinsbroek, R.P.W.; de Bruin, J.P.C.; Laan, J.-B.; Joosten, R.N.J.M.A.; Olivier, B.

    1995-06-01

    Several lines of research have implicated the prefrontal cortex (PFC) and its dopaminergic (DA) innervation in an animal's response to stress and anxiety. To extend these findings we evaluated the effects of bilateral infusions of DA drugs into the medial PFC of rats, in a modified conflict test, consisting of Reward, Conflict and Time-out components. In experiment 1, the effects of infusions of the DA receptor agonist apomorphine (APO) were compared to the effects of systemic injections of the same drug. APO infusions induced a dose-dependent decrease of responding in the Conflict component, indicative of an anxiogenic-like effect. However, response rates in the Reward component were simultaneously decreased, casting some doubt on the specificity of the effect. In comparison, i.p injections of APO in a second group of animals did not affect responding in the Conflict component, but dose-dependently decreased response rates during Time-out and Reward components. In experiment 2, we evaluated the effects of infusions of APO and the DA receptor antagonist cis-flupenthixol (FLU) into the medial PFC in the conflict test, and in one of its variants, the extinction of conflict test. Although both APO and FLU decreased response rates during Reward components, responding in the Conflict components of both tests was differentially affected. APO infusions decreased Conflict responses, the effect being more pronounced in the extinction of conflict test. In contrast, infusions of FLU increased responding in the Conflict components. The respective pro- and anti-conflict effects of APO and FLU infusions are in favour of a direct involvement of prefrontal DA in anxiety-related behavioural responses.

  10. Increase in Prefrontal Cortical Volume following Cognitive Behavioural Therapy in Patients with Chronic Fatigue Syndrome

    Science.gov (United States)

    de Lange, Floris P.; Koers, Anda; Kalkman, Joke S.; Bleijenberg, Gijs; Hagoort, Peter; van der Meer, Jos W. M.; Toni, Ivan

    2008-01-01

    Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an…

  11. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome

    NARCIS (Netherlands)

    Lange, F.P. de; Koers, A.; Kalkman, J.S.; Bleijenberg, G.; Hagoort, Peter; Meer, J.W.M. van der; Toni, I.

    2008-01-01

    Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease.

  12. Successful Face Recognition Is Associated with Increased Prefrontal Cortex Activation in Autism Spectrum Disorder

    Science.gov (United States)

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

    2015-01-01

    This study examines whether deficits in visual information processing in autism-spectrum disorder (ASD) can be offset by the recruitment of brain structures involved in selective attention. During functional MRI, 12 children with ASD and 19 control participants completed a selective attention one-back task in which images of faces and houses were…

  13. Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine

    NARCIS (Netherlands)

    Denys, Damiaan; Klompmakers, André A.; Westenberg, Herman G. M.

    2004-01-01

    RATIONALE: The combination of atypical antipsychotic drugs in addition to serotonin reuptake inhibitors has recently proven to be beneficial in a number of neuropsychiatric disorders, such as major depression, schizophrenia, and obsessive-compulsive disorder. OBJECTIVES: To investigate the effects

  14. The role of prefrontal catecholamines in attention and working memory

    Science.gov (United States)

    Clark, Kelsey L.; Noudoost, Behrad

    2014-01-01

    While much progress has been made in identifying the brain regions and neurochemical systems involved in the cognitive processes disrupted in mental illnesses, to date, the level of detail at which neurobiologists can describe the chain of events giving rise to cognitive functions is very rudimentary. Much of the intense interest in understanding cognitive functions is motivated by the hope that it might be possible to understand these complex functions at the level of neurons and neural circuits. Here, we review the current state of the literature regarding how modulations in catecholamine levels within the prefrontal cortex (PFC) alter the neuronal and behavioral correlates of cognitive functions, particularly attention and working memory. PMID:24782714

  15. 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.

  16. Response of dorsomedial prefrontal cortex predicts altruistic behavior.

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

    2012-05-30

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

  17. Harnessing Prefrontal Cognitive Signals for Brain-Machine Interfaces.

    Science.gov (United States)

    Min, Byoung-Kyong; Chavarriaga, Ricardo; Millán, José Del R

    2017-07-01

    Brain-machine interfaces (BMIs) enable humans to interact with devices by modulating their brain signals. Despite impressive technological advancements, several obstacles remain. The most commonly used BMI control signals are derived from the brain areas involved in primary sensory- or motor-related processing. However, these signals only reflect a limited range of human intentions. Therefore, additional sources of brain activity for controlling BMIs need to be explored. In particular, higher-order cognitive brain signals, specifically those encoding goal-directed intentions, are natural candidates for enlarging the repertoire of BMI control signals and making them more efficient and intuitive. Thus, here, we identify the prefrontal brain area as a key target region for future BMIs, given its involvement in higher-order, goal-oriented cognitive processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Complementary contributions of prefrontal neuron classes in abstract numerical categorization.

    Science.gov (United States)

    Diester, Ilka; Nieder, Andreas

    2008-07-30

    The primate prefrontal cortex (PFC) plays a cardinal role in forming abstract categories and concepts. However, it remains elusive how this is accomplished and to what extent the interaction of functionally distinct neuron classes underlies this representation. Here, we inferred the major cortical cell types, putative pyramidal cells, and interneurons by characterizing the waveforms of action potentials recorded in monkeys performing a cognitively demanding numerosity categorization task. Putative interneurons responded much faster than cells classified as pyramidal neurons and exhibited a higher reliability of category discrimination, whereas putative pyramidal cells showed a higher degree of category selectivity. An analysis of the numerosity tuning profiles and the temporal interactions of adjacent neurons indicated that inhibitory input by putative interneurons shapes the tuning to numerical categories of putative PFC pyramidal cells. These findings favor feedforward mechanisms subserving cognitive categorization and help to clarify cellular interactions in PFC microcircuits.

  19. Prefrontal-hippocampal interactions in memory and emotion

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    Jingji eJin

    2015-12-01

    Full Text Available The hippocampal formation (HPC and medial prefrontal cortex (mPFC have well-established roles in memory encoding and retrieval. However, the mechanisms underlying interactions between the HPC and mPFC in achieving these functions is not fully understood. Considerable research supports the idea that a direct pathway from the HPC and subiculum to the mPFC is critically involved in cognitive and emotional regulation of mnemonic processes. More recently, evidence has emerged that an indirect pathway from the HPC to the mPFC via midline thalamic nucleus reuniens (RE may plays a role in spatial and emotional memory processing. Here we will consider how bidirectional interactions between the HPC and mPFC are involved in working memory, episodic memory and emotional memory in animals and humans. We will also consider how dysfunctions in bidirectional HPC-mPFC pathways contribute to psychiatric disorders.

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

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    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.

  1. Amygdala-prefrontal interactions in (mal)adaptive learning.

    Science.gov (United States)

    Likhtik, Ekaterina; Paz, Rony

    2015-03-01

    The study of neurobiological mechanisms underlying anxiety disorders has been shaped by learning models that frame anxiety as maladaptive learning. Pavlovian conditioning and extinction are particularly influential in defining learning stages that can account for symptoms of anxiety disorders. Recently, dynamic and task related communication between the basolateral complex of the amygdala (BLA) and the medial prefrontal cortex (mPFC) has emerged as a crucial aspect of successful evaluation of threat and safety. Ongoing patterns of neural signaling within the mPFC-BLA circuit during encoding, expression and extinction of adaptive learning are reviewed. The mechanisms whereby deficient mPFC-BLA interactions can lead to generalized fear and anxiety are discussed in learned and innate anxiety. Findings with cross-species validity are emphasized. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Prefrontal control of cerebellum-dependent associative motor learning.

    Science.gov (United States)

    Chen, Hao; Yang, Li; Xu, Yan; Wu, Guang-yan; Yao, Juan; Zhang, Jun; Zhu, Zhi-ru; Hu, Zhi-an; Sui, Jian-feng; Hu, Bo

    2014-02-01

    Behavioral studies have demonstrated that both medial prefrontal cortex (mPFC) and cerebellum play critical roles in trace eyeblink conditioning. However, little is known regarding the mechanism by which the two brain regions interact. By use of electrical stimulation of the caudal mPFC as a conditioned stimulus, we show evidence that persistent outputs from the mPFC to cerebellum are necessary and sufficient for the acquisition and expression of a trace conditioned response (CR)-like response. Specifically, the persistent outputs of caudal mPFC are relayed to the cerebellum via the rostral part of lateral pontine nuclei. Moreover, interfering with persistent activity by blockade of the muscarinic Ach receptor in the caudal mPFC impairs the expression of learned trace CRs. These results suggest an important way for the caudal mPFC to interact with the cerebellum during associative motor learning.

  3. Damage to the ventromedial prefrontal cortex reduces interpersonal disgust.

    Science.gov (United States)

    Ciaramelli, Elisa; Sperotto, Rebecca G; Mattioli, Flavia; di Pellegrino, Giuseppe

    2013-02-01

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

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

    Science.gov (United States)

    Libedinsky, Camilo; Smith, David V; Teng, Chieh Schen; Namburi, Praneeth; Chen, Vanessa W; Huettel, Scott A; Chee, Michael W L

    2011-01-01

    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 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. Mnemonic Encoding and Cortical Organization in Parietal and Prefrontal Cortices.

    Science.gov (United States)

    Masse, Nicolas Y; Hodnefield, Jonathan M; Freedman, David J

    2017-06-21

    Persistent activity within the frontoparietal network is consistently observed during tasks that require working memory. However, the neural circuit mechanisms underlying persistent neuronal encoding within this network remain unresolved. Here, we ask how neural circuits support persistent activity by examining population recordings from posterior parietal (PPC) and prefrontal (PFC) cortices in two male monkeys that performed spatial and motion direction-based tasks that required working memory. While spatially selective persistent activity was observed in both areas, robust selective persistent activity for motion direction was only observed in PFC. Crucially, we find that this difference between mnemonic encoding in PPC and PFC is associated with the presence of functional clustering: PPC and PFC neurons up to ∼700 μm apart preferred similar spatial locations, and PFC neurons up to ∼700 μm apart preferred similar motion directions. In contrast, motion-direction tuning similarity between nearby PPC neurons was much weaker and decayed rapidly beyond ∼200 μm. We also observed a similar association between persistent activity and functional clustering in trained recurrent neural network models embedded with a columnar topology. These results suggest that functional clustering facilitates mnemonic encoding of sensory information. SIGNIFICANCE STATEMENT Working memory refers to our ability to temporarily store and manipulate information. Numerous studies have observed that, during working memory, neurons in higher cortical areas, such as the parietal and prefrontal cortices, mnemonically encode the remembered stimulus. However, several recent studies have failed to observe mnemonic encoding during working memory, raising the question as to why mnemonic encoding is observed during some, but not all, conditions. In this study, we show that mnemonic encoding occurs when a cortical area is organized such that nearby neurons preferentially respond to the same

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

    Science.gov (United States)

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

    2015-10-01

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

  7. Role of the lateral prefrontal cortex in speech monitoring

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    Stephanie K. Riès

    2013-10-01

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

  8. Neuronal coding of auditory sensorimotor gating in medial prefrontal cortex.

    Science.gov (United States)

    Tóth, Attila; Petykó, Zoltán; Gálosi, Rita; Szabó, Imre; Karádi, Kázmér; Feldmann, Ádám; Péczely, László; Kállai, Veronika; Karádi, Zoltán; Lénárd, László

    2017-05-30

    The medial prefrontal cortex (mPFC) is thought to be an essential brain region for sensorimotor gating. The exact neuronal mechanisms, however, have not been extensively investigated yet by delicate single unit recording methods Prepulse inhibition (PPI) of the startle response is a broadly used important tool to investigate the inhibitory processes of sensorimotor gating. The present study was designed to examine the neuronal mechanisms of sensorimotor gating in the mPFC in freely moving rats. In these experiments, the animals were subjected to both pulse alone and prepulse+pulse stimulations. Head acceleration and the neuronal activity of the mPFC were simultaneously recorded. To adequately measure the startle reflex, a new headstage with 3D-accelerometer was created. The duration of head acceleration was longer in pulse alone trials than in prepulse+pulse trial conditions, and the amplitude of head movements was significantly larger during the pulse alone than during the prepulse+pulse situations. Single unit activities in the mPFC were recorded by means of chronically implanted tetrodes during acoustic stimulation evoked startle response and PPI. High proportion of medial prefrontal cortical neurons responded to these stimulations by characteristic firing patterns: short duration equal and unequal excitatory, medium duration excitatory, and long duration excitatory and inhibitory responses were recorded. The present findings, first time in the literature, demonstrated the startle and PPI elicited neuronal activity changes of the mPFC, and thus, provided evidence for a key role of this limbic forebrain area in sensorimotor gating process. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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.

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

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    Xanthippi Konstantoudaki

    2014-03-01

    , we tested whether synaptic plasticity properties of intra-cortical layer II synapses are affected. In adult control mice, tetanic stimulation results in long-term potentiation that lasts at least 50 min (Konstantoudaki et al, 2013. In control mice of the age tested in this study (PD 20-30, LTP could not be induced with the same stimulation. However, we find that Rac1 KO mice do express long-term potentiation. We next studied the dendritic morphology of layer II neurons in the prefrontal cortex, in an effort to identify the mechanism by which Rac1 KO mice exhibit LTP, while the control mice of the same age do not. For this, we stained mouse brains of Rac1 KO and Rac1 heterozygous mice with the Golgi-Cox method. We analyzed the number of secondary apical dendrites, their thickness, as well as the number of spines. We find that the dendrites of pyramidal neurons of Rac1 KO mice have decreased thickness and increased number of spines compared to pyramidal neurons from Rac1 heterozygous mice. These findings could also provide a mechanistic explanation for the presence of LTP in Rac1 KO mice. In conclusion, we find that decreased inhibition during development alters the morphological and functional characteristics of pyramidal neurons in layer II prefrontal cortex of mice. These alterations could provide a cellular substrate for emotional and cognitive dysfunctions present in these mice (Konstantoudaki et al, 2012.

  11. Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2.

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    Melissa L Perreault

    Full Text Available In basal ganglia a significant subset of GABAergic medium spiny neurons (MSNs coexpress D1 and D2 receptors (D1R and D2R along with the neuropeptides dynorphin (DYN and enkephalin (ENK. These coexpressing neurons have been recently shown to have a region-specific distribution throughout the mesolimbic and basal ganglia circuits. While the functional relevance of these MSNs remains relatively unexplored, they have been shown to exhibit the unique property of expressing the dopamine D1-D2 receptor heteromer, a novel receptor complex with distinct pharmacology and cell signaling properties. Here we showed that MSNs coexpressing the D1R and D2R also exhibited a dual GABA/glutamate phenotype. Activation of the D1R-D2R heteromer in these neurons resulted in the simultaneous, but differential regulation of proteins involved in GABA and glutamate production or vesicular uptake in the nucleus accumbens (NAc, ventral tegmental area (VTA, caudate putamen and substantia nigra (SN. Additionally, activation of the D1R-D2R heteromer in NAc shell, but not NAc core, differentially altered protein expression in VTA and SN, regions rich in dopamine cell bodies. The identification of a MSN with dual inhibitory and excitatory intrinsic functions provides new insights into the neuroanatomy of the basal ganglia and demonstrates a novel source of glutamate in this circuit. Furthermore, the demonstration of a dopamine receptor complex with the potential to differentially regulate the expression of proteins directly involved in GABAergic inhibitory or glutamatergic excitatory activation in VTA and SN may potentially provide new insights into the regulation of dopamine neuron activity. This could have broad implications in understanding how dysregulation of neurotransmission within basal ganglia contributes to dopamine neuronal dysfunction.

  12. Stimulus selectivity in dorsal and ventral prefrontal cortex after training in working memory tasks

    Science.gov (United States)

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

    2011-01-01

    The prefrontal cortex is known to represent different types of information in working memory. Contrasting theories propose that the dorsal and ventral regions of the lateral prefrontal cortex are innately specialized for the representation of spatial and non-spatial information respectively (Goldman-Rakic, 1996), or that the two regions are shaped by the demands of cognitive tasks imposed on them (Miller, 2000). To resolve this issue, we recorded from neurons in the two regions, prior to and at multiple stages of training monkeys on visual working memory tasks. Prior to training, substantial functional differences were present between the two regions. Dorsal prefrontal cortex exhibited higher overall responsiveness to visual stimuli and higher selectivity for spatial information. After training, stimulus selectivity generally decreased, though dorsal prefrontal cortex retained higher spatial selectivity regardless of task performed. Ventral prefrontal cortex appeared to be affected to a greater extent by the nature of task performed. Our results indicate that regional specialization for stimulus selectivity is present in the primate prefrontal cortex regardless of training. Dorsal areas of the prefrontal cortex are inherently organized to represent spatial information and training has little influence on this spatial bias. Ventral areas are biased toward non-spatial information although they are more influenced by training both in terms of activation and changes in stimulus selectivity. PMID:21525266

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

    Science.gov (United States)

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

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Right prefrontal cortex transcranial direct current stimulation enhances multi-day savings in sensorimotor adaptation.

    Science.gov (United States)

    Seidler, Rachael D; Gluskin, Brittany S; Greeley, Brian

    2017-01-01

    We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of visuomotor adaptation. Recent behavioral studies suggest that sensorimotor savings, or faster relearning on second exposure to a task, are due to recall of these early, strategic components of adaptation. In the present study we applied anodal transcranial direct current stimulation to right or left prefrontal cortex or left motor cortex. We found that all groups adapted dart throwing movements while wearing prism lenses at the same rate as subjects receiving sham stimulation on day 1 On test day 2, which was conducted a few days later, the right prefrontal and left motor cortex groups adapted faster than the sham group. Moreover, only the right prefrontal group exhibited greater savings, expressed as a greater difference between day 1 and day 2 errors, compared with sham stimulation. These findings support the hypothesis that the right prefrontal cortex contributes to sensorimotor adaptation and savings. We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of manual visuomotor adaptation. Sensorimotor savings, or faster adaptation to a previously experienced perturbation, has been recently linked to cognitive processes. We show that facilitating the right prefrontal cortex with anodal transcranial direct current stimulation enhances sensorimotor savings compared with sham stimulation. Copyright © 2017 the American Physiological Society.

  15. Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation.

    Science.gov (United States)

    Rame, Marion; Caudal, Dorian; Schenker, Esther; Svenningsson, Per; Spedding, Michael; Jay, Thérèse M; Godsil, Bill P

    2017-01-01

    Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat's hippocampus-to-prefrontal cortex (H-PFC) pathway. We found that a low dose of ketamine depressed H-PFC LTP, whereas animals that were co-administrated the two drugs displayed LTP that was similar to a saline-treated control. To address which signaling molecules might mediate such effects, we also examined phosphorylation and total protein levels of GSK3β, GluA1, TrkB, ERK, and mTOR in prefrontal and hippocampal sub-regions. Among the statistically significant effects that were detected (a) both ketamine and clozapine increased the phosphorylation of Ser9-GSK3β throughout the prefrontal cortex and of Ser2481-mTOR in the dorsal hippocampus (DH), (b) clozapine increased the phosphorylation of Ser831-GluA1 throughout the prefrontal cortex and of Ser845-GluA1 in the ventral hippocampus, (c) ketamine treatment increased the phosphorylation of Thr202/Tyr204-ERK in the medial PFC (mPFC), and (d) clozapine treatment was associated with decreases in the phosphorylation of Tyr705-TrkB in the DH and of Try816-TrkB in the mPFC. Further analyses involving phosphorylation effect sizes also suggested Ser831-GluA1 in the PFC displayed the highest degree of clozapine-responsivity relative to ketamine. These results provide evidence for how ketamine and clozapine treatments affect neuroplasticity and signaling pathways in the stress-sensitive H-PFC network. They also demonstrate the potential relevance of H-PFC pathway

  16. Impairment in Delayed Non-Matching to Sample Following Lesions of Dorsal Prefrontal Cortex

    OpenAIRE

    Moore, Tara L.; Schettler, Stephen P.; Killiany, Ronald J.; Rosene, Douglas L.; Moss, Mark B.

    2012-01-01

    The prefrontal cortex has been identified as essential for executive function, as well as for aspects of rule learning and recognition memory. As part of our studies to assess prefrontal cortical function in the monkey, we evaluated the effects of damage to the dorsal prefrontal cortex (DPFC) on the Category Set Shifting Task (CSST), a test of abstraction and set-shifting, and on the Delayed Non Matching-to-Sample (DNMS) task, a benchmark test of rule learning and recognition memory. The DPFC...

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

    Science.gov (United States)

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

    2011-12-01

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

  18. Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Tariq Waseem Chohan

    2014-09-01

    Full Text Available Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1 and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET and wild-type (WT mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV and the dentate gyrus (DG of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.

  19. Evidence in chronic fatigue syndrome for severity-dependent upregulation of prefrontal myelination that is independent of anxiety and depression.

    Science.gov (United States)

    Barnden, Leighton R; Crouch, Benjamin; Kwiatek, Richard; Burnet, Richard; Del Fante, Peter

    2015-03-01

    White matter (WM) involvement in chronic fatigue syndrome (CFS) was assessed using voxel-based regressions of brain MRI against CFS severity scores and CFS duration in 25 subjects with CFS and 25 normal controls (NCs). As well as voxel-based morphometry, a novel voxel-based quantitative analysis of T1 - and T2 -weighted spin-echo (T1w and T2w) MRI signal level was performed. Severity scores included the Bell CFS disability scale and scores based on the 10 most common CFS symptoms. Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores were included as nuisance covariates. By relaxing the threshold for cluster formation, we showed that the T1w signal is elevated with increasing CFS severity in the ventrolateral thalamus, internal capsule and prefrontal WM. Earlier reports of WM volume losses and neuroinflammation in the midbrain, together with the upregulated prefrontal myelination suggested here, are consistent with the midbrain changes being associated with impaired nerve conduction which stimulates a plastic response on the cortical side of the thalamic relay in the same circuits. The T2w signal versus CFS duration and comparison of T2w signal in the CFS group with the NC group revealed changes in the right middle temporal lobe WM, where impaired communication can affect cognitive function. Adjustment for depression markedly strengthened cluster statistics and increased cluster size in both T1w severity regressions, but adjustment for anxiety less so. Thus, depression and anxiety are statistical confounders here, meaning that they contribute variance to the T1w signal in prefrontal WM but this does not correlate with the co-located variance from CFS severity. MRI regressions with depression itself only detected associations with WM volume, also located in prefrontal WM. We propose that impaired reciprocal brain-body and brain-brain communication through the midbrain provokes peripheral and central responses which contribute to CFS symptoms

  20. Adrenocortical status predicts the degree of age-related deficits in prefrontal structural plasticity and working memory.

    Science.gov (United States)

    Anderson, Rachel M; Birnie, Andrew K; Koblesky, Norah K; Romig-Martin, Sara A; Radley, Jason J

    2014-06-18

    Cognitive decline in aging is marked by considerable variability, with some individuals experiencing significant impairments and others retaining intact functioning. Whereas previous studies have linked elevated hypothalamo-pituitary-adrenal (HPA) axis activity with impaired hippocampal function during aging, the idea has languished regarding whether such differences may underlie the deterioration of other cognitive functions. Here we investigate whether endogenous differences in HPA activity are predictive of age-related impairments in prefrontal structural and behavioral plasticity. Young and aged rats (4 and 21 months, respectively) were partitioned into low or high HPA activity, based upon averaged values of corticosterone release from each animal obtained from repeated sampling across a 24 h period. Pyramidal neurons in the prelimbic area of medial prefrontal cortex were selected for intracellular dye filling, followed by 3D imaging and analysis of dendritic spine morphometry. Aged animals displayed dendritic spine loss and altered geometric characteristics; however, these decrements were largely accounted for by the subgroup bearing elevated corticosterone. Moreover, high adrenocortical activity in aging was associated with downward shifts in frequency distributions for spine head diameter and length, whereas aged animals with low corticosterone showed an upward shift in these indices. Follow-up behavioral experiments revealed that age-related spatial working memory deficits were exacerbated by increased HPA activity. By contrast, variations in HPA activity in young animals failed to impact structural or behavioral plasticity. These data implicate the cumulative exposure to glucocorticoids as a central underlying process in age-related prefrontal impairment and define synaptic features accounting for different trajectories in age-related cognitive function. Copyright © 2014 the authors 0270-6474/14/348387-11$15.00/0.

  1. Prefrontal control of the amygdala during real-time fMRI neurofeedback training of emotion regulation.

    Directory of Open Access Journals (Sweden)

    Vadim Zotev

    Full Text Available We observed in a previous study (PLoS ONE 6:e24522 that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC, bilateral dorsomedial prefrontal cortex (DMPFC, bilateral superior frontal gyrus (SFG, and right medial frontopolar cortex (MFPC. Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a significant enhancement in the time-lagged effect of the left rACC on the LA, potentially consistent with the ipsilateral distribution of the monosynaptic projections between these regions. The training is also accompanied by significant increases in the instantaneous (contemporaneous effects of the left rACC on four other regions - the bilateral DMPFC, the right MFPC, and the left SFG. The instantaneous effects of the LA on the bilateral DMPFC are also significantly enhanced. Our results are consistent with a broad literature supporting the role of the rACC in emotion processing and regulation. Our exploratory analysis provides, for the first time, insights into the causal relationships within the network of regions engaged during the rtfMRI-nf procedure targeting the amygdala. It suggests that the rACC may constitute a promising target for rtfMRI-nf training along with the amygdala in patients with affective disorders, particularly posttraumatic stress

  2. Functional connectivity changes between parietal and prefrontal cortices in primary insomnia patients: evidence from resting-state fMRI

    Science.gov (United States)

    2014-01-01

    Background Primary insomnia can severely impair daytime function by disrupting attention and working memory and imposes a danger to self and others by increasing the risk of accidents. We speculated that the neurobiological changes impeding working memory in primary insomnia patients would be revealed by resting-state functional MRI (R-fMRI), which estimates the strength of cortical pathways by measuring local and regional correlations in blood oxygen level dependent (BOLD) signs independent of specific task demands. Methods We compared the R-fMRI activity patterns of 15 healthy controls to 15 primary insomnia patients (all 30 participants were right-handed) using a 3.0 T MRI scanner. The SPM8 and REST1.7 software packages were used for preprocessing and analysis. Activity was expressed relative to the superior parietal lobe (SPL, the seed region) to reveal differences in functional connectivity to other cortical regions implicated in spatial working memory. Result In healthy controls, bilateral SPL activity was associated with activity in the posterior cingulate gyrus, precuneus, ventromedial prefrontal cortex, and superior frontal gyrus, indicating functional connectivity between these regions. Strong functional connectivity between the SPL and bilateral pre-motor cortex, bilateral supplementary motor cortex, and left dorsolateral prefrontal cortex was observed in both the control group and the primary insomnia group. However, the strength of several other functional connectivity pathways to the SPL exhibited significant group differences. Compared to healthy controls, connectivity in the primary insomnia group was stronger between the bilateral SPL and the right ventral anterior cingulate cortex, left ventral posterior cingulate cortex, right splenium of the corpus callosum, right pars triangularis (right inferior frontal gyrus/Broca’s area), and right insular lobe, while connectivity was weaker between the SPL and right superior frontal gyrus (dorsolateral

  3. Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting.

    Science.gov (United States)

    Liston, Conor; Miller, Melinda M; Goldwater, Deena S; Radley, Jason J; Rocher, Anne B; Hof, Patrick R; Morrison, John H; McEwen, Bruce S

    2006-07-26

    Stressful life events have been implicated clinically in the pathogenesis of mental illness, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of these psychiatric conditions are associated with structural and functional abnormalities in a network of prefrontal cortical structures. Here, we examine whether chronic stress-induced dendritic alterations in the medial prefrontal cortex (mPFC) and orbital frontal cortex (OFC) underlie impairments in the behaviors that they subserve. After 21 d of repeated restraint stress, rats were tested on a perceptual attentional set-shifting task, which yields dissociable measures of reversal learning and attentional set-shifting, functions that are mediated by the OFC and mPFC, respectively. Intracellular iontophoretic injections of Lucifer yellow were performed in a subset of these rats to examine dendritic morphology in layer II/III pyramidal cells of the mPFC and lateral OFC. Chronic stress induced a selective impairment in attentional set-shifting and a corresponding retraction (20%) of apical dendritic arbors in the mPFC. In stressed rats, but not in controls, decreased dendritic arborization in the mPFC predicted impaired attentional set-shifting performance. In contrast, stress was not found to adversely affect reversal learning or dendritic morphology in the lateral OFC. Instead, apical dendritic arborization in the OFC was increased by 43%. This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.

  4. Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective.

    Science.gov (United States)

    Ding, Y; Lawrence, N; Olié, E; Cyprien, F; le Bars, E; Bonafé, A; Phillips, M L; Courtet, P; Jollant, F

    2015-02-24

    The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research.

  5. [Morphological study of neuroprotective properties of dipeptide mimetic of nerve growth factor (GK-2h) in focal ischemic damage of rat brain prefrontal cortex].

    Science.gov (United States)

    Barskov, I V; Stelmashuk, E V; Romanova, G A; Khaspekov, L G

    2013-01-01

    The neuroprotective effects of dipeptide GK-2h, a mimetic of nerve growth factor, in bifocal photoinduced ischemia in rat brain prefrontal cortex was studied. It was shown that GK-2h, injected intraperitonealy in dose 0.1 mg/kg in 1 h or 4 h after operation and then on 2nd, 4th and 8th days, prevented significantly on 9th day from increasing volume of cortical infarction.

  6. Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms

    DEFF Research Database (Denmark)

    Eriksson, Olle; Wall, Anders; Olsson, Ulf

    2016-01-01

    in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral...... prefrontal cortex, putamen and caudate nucleus, and the single "whole brain". RESULTS: There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant...... quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual...

  7. Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias.

    Science.gov (United States)

    Foster, Vincent; Oakley, Arthur E; Slade, Janet Y; Hall, Roslyn; Polvikoski, Tuomo M; Burke, Matthew; Thomas, Alan J; Khundakar, Ahmad; Allan, Louise M; Kalaria, Raj N

    2014-09-01

    dementia ratings. Total estimated neuronal densities were not significantly changed between patients with post-stroke dementia and post-stroke patients with no dementia groups or ageing controls in any of the three frontal regions. In further morphometric analysis of the dorsolateral prefrontal cortex, we showed that neither diffuse cerebral atrophy nor neocortical thickness explained the selective neuronal volume effects. We also noted that neurofilament protein SMI31 immunoreactivity was increased in post-stroke and vascular dementia compared with post-stroke patients with no dementia and correlated with decreased neuronal volumes in subjects with post-stroke dementia and vascular dementia. Our findings suggest selective regional pyramidal cell atrophy in the dorsolateral prefrontal cortex-rather than neuronal density changes per se-are associated with dementia and executive dysfunction in post-stroke dementia and vascular dementia. The changes in dorsolateral prefrontal cortex pyramidal cells were not associated with neurofibrillary pathology suggesting there is a vascular basis for the observed highly selective neuronal atrophy. © 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.

  8. Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex.

    NARCIS (Netherlands)

    Qin, S.; Hermans, E.J.; Marle, H.J.F. van; Luo, J.; Fernandez, G.S.E.

    2009-01-01

    BACKGROUND: Acute psychological stress impairs higher-order cognitive function such as working memory (WM). Similar impairments are seen in various psychiatric disorders that are associated with higher susceptibility to stress and with prefrontal cortical dysfunctions, suggesting that acute stress

  9. Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory

    National Research Council Canada - National Science Library

    Hanson, Jamie L; Chung, Moo K; Avants, Brian B; Rudolph, Karen D; Shirtcliff, Elizabeth A; Gee, James C; Davidson, Richard J; Pollak, Seth D

    2012-01-01

    .... Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter...

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

    National Research Council Canada - National Science Library

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

    2014-01-01

    .... Here we show in a unique sample of neurological patients that focal lesions involving ventromedial prefrontal cortex, acquired during development, result in an abnormally egocentric pattern of moral judgement...

  11. Levodopa reinstates connectivity from prefrontal to premotor cortex during externally paced movement in Parkinson's disease

    DEFF Research Database (Denmark)

    Herz, Damian M; Siebner, Hartwig R; Hulme, Oliver J

    2014-01-01

    to examine oscillatory coupling between prefrontal and premotor areas during respectively low and high levels of dopamine. In 10 patients and 12 control participants multiple source beamformer analysis yielded task-related activation of a contralateral cortical network comprising prefrontal cortex (PFC......), lateral premotor cortex (lPM), supplementary motor area (SMA) and primary motor cortex (M1). Dynamic causal modelling was used to characterize task-related oscillatory coupling between prefrontal and premotor cortical areas. Healthy participants showed task-induced coupling from PFC to SMA, which......Dopamine deficiency affects functional integration of activity in distributed neural regions. It has been suggested that lack of dopamine induces disruption of neural interactions between prefrontal and premotor areas, which might underlie impairment of motor control observed in patients...

  12. Antipsychotic medication and prefrontal cortex activation : A review of neuroimaging findings

    NARCIS (Netherlands)

    Liemburg, Edith J.; Knegtering, Henderikus; Klein, Hans C.; Kortekaas, Rudie; Aleman, Andre

    Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which

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

    NARCIS (Netherlands)

    Poorthuis, R.B.; Bloem, B.; 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

  14. Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

    Science.gov (United States)

    Mulder, Martijn J.; Baeyens, Dieter; Davidson, Matthew C.; Casey, B. J.; Van Den Ban, Els; Van Engeland, Herman; Durston, Sarah

    2008-01-01

    The study examines whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. The results conclude that familial vulnerability to ADHD affects activity in both the prefrontal cortex and cerebellum.

  15. [Effect of Reading a Book on a Tablet Computer on Cerebral Blood Flow in the Prefrontal Cortex].

    Science.gov (United States)

    Sugiura, Akihiro; Eto, Takuya; Kinoshita, Fumiya; Takada, Hiroki

    2018-01-01

    By measuring cerebral blood flow in the prefrontal cortex, we aimed to determine how reading a book on a tablet computer affects sleep. Seven students (7 men age range, 21-32 years) participated in this study. In a controlled illuminance environment, the subjects read a novel in printed form or on a tablet computer from any distance. As the subjects were reading, the cerebral blood flow in their prefrontal cortex was measured by near-infrared spectroscopy. The study protocol was as follows. 1) Subjects mentally counted a sequence of numbers for 30 s as a pretest to standardized thinking and then 2) read the novel for 10 min, using the printed book or tablet computer. In step 2), the use of the book or tablet computer was in a random sequence. Subjects rested between the two tasks. Significantly increased brain activity (increase in regional cerebral blood flow) was observed following reading a novel on a tablet computer compared with that after reading a printed book. Furthermore, the region around Broca's area was more active when reading on a tablet computer than when reading a printed book. Considering the results of this study and previous studies on physiological characteristics during nonrapid eye movement sleep, we concluded that reading a book on a tablet computer before the onset of sleep leads to the potential inhibition of sound sleep through mechanisms other than the suppression of melatonin secretion.

  16. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide.

    Science.gov (United States)

    Zhao, J; Verwer, R W H; van Wamelen, D J; Qi, X-R; Gao, S-F; Lucassen, P J; Swaab, D F

    2016-11-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the neuronal/glial glutamate transporters was determined by qPCR in postmortem prefrontal cortex. The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) were selected from young MDD patients who had committed suicide (MDD-S; n = 17), from MDD patients who died of non-suicide related causes (MDD-NS; n = 7) and from matched control subjects (n = 12). We also compared elderly depressed patients who had not committed suicide (n = 14) with matched control subjects (n = 22). We found that neuronal located components (EAAT3, EAAT4, ASCT1, SNAT1, SNAT2) of the glutamate-glutamine cycle were increased in the ACC while the astroglia located components (EAAT1, EAAT2, GLUL) were decreased in the DLPFC of MDD-S patients. In contrast, most of the components in the cycle were increased in the DLPFC of MDD-NS patients. In conclusion, the glutamate-glutamine cycle - and thus glutamine transmission - is differentially affected in depressed suicide patients and depressed non-suicide patients in an area specific way. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Ruocco, Anthony C.; Rodrigo, Achala H.; McMain, Shelley F.; Page-Gould, Elizabeth; Ayaz, Hasan; Links, Paul S.

    2016-01-01

    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, 29 actively self-harming patients with BPD completed brain-imaging procedures probing activation of the prefrontal cortex (PFC) during impulse control prior to beginning DBT and after 7 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 (DLPFC) prior to beginning treatment, and they showed the greatest increases in activity within this region after 7 months of treatment. Prior to starting DBT, treatment non-completers demonstrated greater activation than treatment-completers in the medial PFC and right inferior frontal gyrus. Reductions in self-harm over the treatment period were associated with increases in activity in right DLPFC even after accounting for improvements in depression, mania, and BPD symptom severity. These findings suggest that pre-treatment patterns of activation in the PFC underlying impulse control may be prospectively associated with improvements in self-harm and treatment attrition for patients with BPD treated with DBT. PMID:27242484

  18. 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 × 10 9 asymmetric synapses, 1.06 × 10 8 symmetric synapses and 1.00 × 10 8 myelinated axons. The density of asymmetric synapses was 5.5/μm 3 and the density of symmetric synapses was 0.5/μm 3 . 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

  19. 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

  20. Prefrontal activation in response to emotional words in patients with bipolar disorder and major depressive disorder.

    Science.gov (United States)

    Matsubara, Toshio; Matsuo, Koji; Nakashima, Mami; Nakano, Masayuki; Harada, Kenichiro; Watanuki, Toshio; Egashira, Kazuteru; Watanabe, Yoshifumi

    2014-01-15

    Abnormal emotional processing is involved in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether the neural mechanism underlying this deficit is a trait characteristic of BD and MDD is unclear. The aim of this study was to elucidate the similarities and differences in processing of emotional stimuli between patients with BD and MDD in remission, using functional near-infrared spectroscopy (fNIRS). Thirty-two patients (16 with BD and 16 with MDD) and 20 healthy control subjects matched for age, sex, handedness, and years of education were included. An emotional Stroop task, including happy, sad, and threat words, was used. The relative oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) changes in the frontal region were measured using 52-channels of NIRS. During the threat task, compared to healthy control subjects, patients with BD showed significantly increased [oxy-Hb] in the left inferior frontal region whereas patients with MDD showed significantly increased [oxy-Hb] in the left middle frontal region. During the happy task, compared to healthy control subjects, patients with BD showed significantly decreased [oxy-Hb] in the middle frontal region in both hemispheres. Moreover, patients with BD exhibited decreased [oxy-Hb] and increased [deoxy-Hb] in the superior frontal and middle frontal regions compared to MDD in response to the happy stimulus. No significant differences in [oxy-Hb] or [deoxy-Hb] were seen between the groups during the sad task. These results suggest that abnormal neural responses to emotional stimuli in patients with mood disorders in remission may be a trait characteristic, that negative emotional stimuli are associated with similar prefrontal responses, and that positive emotional stimuli are associated with different prefrontal responses in patients with BD and MDD. These findings indicate that different neural circuits play a role in emotional processing in BD and

  1. Role of Prefrontal Cortex in Learning and Generalizing Hierarchical Rules in 8-Month-Old Infants.

    Science.gov (United States)

    Werchan, Denise M; Collins, Anne G E; Frank, Michael J; Amso, Dima

    2016-10-05

    Recent research indicates that adults and infants spontaneously create and generalize hierarchical rule sets during incidental learning. Computational models and empirical data suggest that, in adults, this process is supported by circuits linking prefrontal cortex (PFC) with striatum and their modulation by dopamine, but the neural circuits supporting this form of learning in infants are largely unknown. We used near-infrared spectroscopy to record PFC activity in 8-month-old human infants during a simple audiovisual hierarchical-rule-learning task. Behavioral results confirmed that infants adopted hierarchical rule sets to learn and generalize spoken object-label mappings across different speaker contexts. Infants had increased activity over right dorsal lateral PFC when rule sets switched from one trial to the next, a neural marker related to updating rule sets into working memory in the adult literature. Infants' eye blink rate, a possible physiological correlate of striatal dopamine activity, also increased when rule sets switched from one trial to the next. Moreover, the increase in right dorsolateral PFC activity in conjunction with eye blink rate also predicted infants' generalization ability, providing exploratory evidence for frontostriatal involvement during learning. These findings provide evidence that PFC is involved in rudimentary hierarchical rule learning in 8-month-old infants, an ability that was previously thought to emerge later in life in concert with PFC maturation. Hierarchical rule learning is a powerful learning mechanism that allows rules to be selected in a context-appropriate fashion and transferred or reused in novel contexts. Data from computational models and adults suggests that this learning mechanism is supported by dopamine-innervated interactions between prefrontal cortex (PFC) and striatum. Here, we provide evidence that PFC also supports hierarchical rule learning during infancy, challenging the current dogma that PFC is an

  2. Dynamic changes in prefrontal cortex gene expression following lysergic acid diethylamide administration.

    Science.gov (United States)

    Nichols, Charles D; Garcia, Efrain E; Sanders-Bush, Elaine

    2003-03-17

    Lysergic acid diethylamide (LSD) is a psychoactive drug that transiently alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia. Characterizing gene expression profiles after LSD will be important for understanding how it alters behavior, and will lead to novel insights into disorders, such as schizophrenia, whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs. We previously identified a small collection of genes within the rat prefrontal cortex that respond to LSD. Many of the products of these genes are involved in the process of synaptic plasticity. In the current report, we present a detailed analysis of the expression of these genes within the brain using RNase protection analysis. We find that the gene response to LSD is quite dynamic. The expression of some genes increases rapidly and decreases rapidly, while other genes change more gradually. Dose-response studies show two classes of expression; gene expression maximally stimulated at lower doses, versus gene expression that continues to rise at the higher doses. The role of the 5-HT(1A) and 5-HT(2A) receptor in mediating the increases in gene expression was examined in a series of experiments using receptor specific antagonists. Most expression increases were due to activation of the 5-HT(2A) receptor, however expression of two genes had neither a 5-HT(1A) nor a 5-HT(2A) receptor component.

  3. Dorsolateral prefrontal cortex modulates striatal reward encoding during reappraisal of reward anticipation.

    Science.gov (United States)

    Staudinger, Markus R; Erk, Susanne; Walter, Henrik

    2011-11-01

    Recent research showed that cognitive emotion regulation (ER) both increases activity in the dorsolateral prefrontal cortex (DLPFC) and decreases striatal responsivity to monetary rewards. Using a mixed monetary incentive delay/memory task as well as functional magnetic resonance imaging, we tested in healthy subjects whether ER effectively attenuates striatal reward encoding during the anticipation of reward (€1.00 vs. €0.05 reward cues) as well as subsequent target reaction times (RTs), which are an indicator of motivation to obtain reward. ER significantly diminished feelings of pleasant anticipation and slowed down €1.00 target RT. At the neural level, ER increased activity in the DLPFC and attenuated reward encoding in the left putamen. Analyses of psychophysiological interaction revealed that DLPFC activity correlated more positively with putamen activity during €0.05 than during €1.00 reward trials. Furthermore, parametric modulations showed that anticipatory left putamen activity correlated with target RT during nonregulation. No such correlation could be observed during ER, suggesting that ER had abolished preparatory target RT encoding. Our results provide evidence that ER can attenuate behavioral and striatal measures of reward-related motivation and motor preparation. Furthermore, the present findings suggest that the DLPFC might contribute to successful regulation of reward via increased promotion of low-reward responses.

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

    Science.gov (United States)

    Stumbrys, Tadas; Erlacher, Daniel; Schredl, Michael

    2013-12-01

    Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming) might be associated with increased brain activity over frontal regions during rapid eye movement (REM) sleep. By applying transcranial direct current stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen participants spent three consecutive nights in a sleep laboratory. On the second and third nights they randomly received either 1 mA tDCS for 10 min or sham stimulation during each REM period starting with the second one. According to the participants' self-ratings, tDCS over the DLPFC during REM sleep increased lucidity in dreams. The effects, however, were not strong and found only in frequent lucid dreamers. While this indicates some preliminary support for the involvement of the DLPFC in lucid dreaming, further research, controlling for indirect effects of stimulation and including other brain regions, is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Neuroendocrine stress responses predict catecholamine-dependent working memory-related dorsolateral prefrontal cortex activity.

    Science.gov (United States)

    Hernaus, Dennis; Quaedflieg, Conny W E M; Offermann, Jan Stefan; Casales Santa, Marta M; van Amelsvoort, Thérèse

    2018-01-01

    It is generally thought that the effect of acute stress on higher-order functions such as working memory is, for an important part, mediated by central catecholamine activity. However, little is known about the association between neuroendocrine stress responses and catecholamine-dependent working memory-related brain function in the absence of stress. Here, we investigate for the first time in healthy humans (n = 18) how neuroendocrine responses to stress (cortisol and alpha-amylase) relate to fronto-parietal working memory activity changes in response to atomoxetine, a noradrenaline transporter inhibitor that selectively increases extracellular cortical dopamine and noradrenaline. We observed positive correlations between stress-induced cortisol (Pearson's r = 0.75, P working memory-related activity in dorsolateral prefrontal cortex. Stress-induced cortisol increases furthermore correlated with supramarginal gyrus working memory-related activity (r = 0.79, P working memory activity on placebo and greater working memory activity increases following atomoxetine in high stress responders. These results further corroborate the notion that neuroendocrine responses to stress are an informative proxy of catecholamine function relevant to higher order functions and provide novel hints on the complex relationship between acute stress, catecholamine function and working memory. © The Author (2017). Published by Oxford University Press.

  6. Damage to dorsolateral prefrontal cortex affects tradeoffs between honesty and self-interest.

    Science.gov (United States)

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

    2014-10-01

    Substantial correlational evidence suggests that prefrontal regions are critical to honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. We found that lesions of the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions when honesty concerns were absent. These results point to a causal role for DLPFC in honest behavior.

  7. Advances in understanding ventromedial prefrontal function: the accountant joins the executive.

    Science.gov (United States)

    Fellows, Lesley K

    2007-03-27

    Studies of the brain basis of decision-making and economic behavior are providing a new perspective on the organization and functions of human prefrontal cortex. This line of inquiry has focused particularly on the ventral and medial portions of prefrontal cortex, arguably the most enigmatic regions of the "enigmatic frontal lobes." This review highlights recent advances in the cognitive neuroscience of decision making and neuroeconomics and discusses how these findings can inform clinical thinking about frontal lobe dysfunction.

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

    Science.gov (United States)

    Funahashi, Shintaro

    2015-01-01

    Working memory (WM) 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 WM 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 WM 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Comparison of strategy signals in the dorsolateral and orbital prefrontal cortex

    OpenAIRE

    Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P.

    2011-01-01

    Abstract behavior-guiding rules and strategies allow monkeys to avoid errors in rarely encountered situations. In the present study, we contrasted strategy-related neuronal activity in the dorsolateral prefrontal cortex (PFdl) and the orbital prefrontal cortex (PFo) of rhesus monkeys. On each trial of their behavioral task, the monkeys responded to a foveal visual cue by making a saccade to one of two spatial targets. One response required a leftward saccade; the other required a saccade of e...

  11. Prefrontal Brain Activation During Emotional Processing: A Functional Near Infrared Spectroscopy Study (fNIRS).

    Science.gov (United States)

    Glotzbach, Evelyn; Mühlberger, Andreas; Gschwendtner, Kathrin; Fallgatter, Andreas J; Pauli, Paul; Herrmann, Martin J

    2011-01-01

    The limbic system and especially the amygdala have been identified as key structures in emotion induction and regulation. Recently research has additionally focused on the influence of prefrontal areas on emotion processing in the limbic system and the amygdala. Results from fMRI studies indicate that the prefrontal cortex (PFC) is involved not only in emotion induction but also in emotion regulation. However, studies using fNIRS only report prefrontal brain activation during emotion induction. So far it lacks the attempt to compare emotion induction and emotion regulation with regard to prefrontal activation measured with fNIRS, to exclude the possibility that the reported prefrontal brain activation in fNIRS studies are mainly caused by automatic emotion regulation processes. Therefore this work tried to distinguish emotion induction from regulation via fNIRS of the prefrontal cortex. 20 healthy women viewed neutral pictures as a baseline condition, fearful pictures as induction condition and reappraised fearful pictures as regulation condition in randomized order. As predicted, the view-fearful condition led to higher arousal ratings than the view-neutral condition with the reappraise-fearful condition in between. For the fNIRS results the induction condition showed an activation of the bilateral PFC compared to the baseline condition (viewing neutral). The regulation condition showed an activation only of the left PFC compared to the baseline condition, although the direct comparison between induction and regulation condition revealed no significant difference in brain activation. Therefore our study underscores the results of previous fNIRS studies showing prefrontal brain activation during emotion induction and rejects the hypothesis that this prefrontal brain activation might only be a result of automatic emotion regulation processes.

  12. Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults.

    Directory of Open Access Journals (Sweden)

    Erika E Forbes

    Full Text Available Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings

  13. FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices of human alcoholics

    OpenAIRE

    Watanabe, Hiroyuki; Henriksson, Richard; Ohnishi, Yoshinori N.; Ohnishi, Yoko H.; Harper, Clive; Sheedy, Donna; Garrick, Therese; Nyberg, Fred; Nestler, Eric J.; Bakalkin, Georgy; Yakovleva, Tatjana

    2009-01-01

    The transcription factor DeltaFosB is accumulated in the addiction circuitry, including the orbitofrontal and medial prefrontal cortices of rodents chronically exposed to ethanol or other drugs of abuse, and has been suggested to play a direct role in addiction maintenance. To address this hypothesis in the context of substance dependence in humans, we compared the immunoreactivities of FOSB proteins in the orbitofrontal and dorsolateral prefrontal cortices (OFC and DLPFC respectively) betwee...

  14. Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults.

    Science.gov (United States)

    Forbes, Erika E; Rodriguez, Eric E; Musselman, Samuel; Narendran, Rajesh

    2014-01-01

    Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant

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

    Directory of Open Access Journals (Sweden)

    Bettina Studer

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

  16. 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.

  17. 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

    2015-01-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies. PMID:25450230

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

    Science.gov (United States)

    Moriya, M; Aoki, C; Sakatani, K

    2016-01-01

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

  19. Prelimbic prefrontal cortex mediates respiratory responses to mild and potent prolonged, but not brief, stressors.

    Science.gov (United States)

    Bondarenko, E; Hodgson, D M; Nalivaiko, E

    2014-12-01

    The prefrontal cortex is one of the key areas of the central mechanism of cardiovascular and respiratory control. Disinhibition of the prelimbic medial prefrontal cortex elicits tachypnoeic responses in anesthetized rats (Hassan et al., J. Physiol. 591: 6069-6088, 2013). The current study examines the effects of inhibition of the prelimbic prefrontal cortex during presentation of stressors of various lengths and intensities in conscious unrestrained rats. 8 Wistar rats were implanted with bilateral guide cannulas targeting the prelimbic prefrontal cortex and received microinjections of either saline of GABAA agonist muscimol prior to recording sessions. Inhibition of the prelimbic prefrontal cortex significantly attenuated respiratory responses to a novel environment stress, 30s light stimulus and restraint stress. It did not affect respiratory responses to 500 ms acoustic stimuli of varying intensities (40-90 dB). We conclude that the prelimbic prefrontal cortex contributes to generation of tachypnoeic responses to prolonged stressors, but does not contribute to respiratory arousal in response to brief stressors. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Positive allosteric modulators of the α7 nicotinic acetylcholine receptor potentiate glutamate release in the prefrontal cortex of freely-moving rats

    DEFF Research Database (Denmark)

    Bortz, D M; Upton, B A; Mikkelsen, J D

    2016-01-01

    such studies have been performed in vitro. Here we test the hypothesis that PAMs’ potentiation of glutamate release in prefrontal cortex depends upon the level of endogenous cholinergic activity. NMDA stimulation of the nucleus accumbens shell (0.05–0.30 μg in 0.5 μL) increased extracellular choline (0.87 ± 0.......15 – 1.73 ± 0.31 μM) and glutamate (0.15 μg, 3.79 ± 0.87 μM) in medial prefrontal cortex, and the glutamate release was prevented by local infusions of MLA (6.75 μg, 0.19 ± 0.06 μM). The lower dose (1 mg/kg) of AVL3288 (type I) potentiated the glutamate release to a greater degree after the high dose...

  1. Impact of anxiety on prefrontal cortex encoding of cognitive flexibility.

    Science.gov (United States)

    Park, Junchol; Moghaddam, Bita

    2017-03-14

    Anxiety often is studied as a stand-alone construct in laboratory models. But in the context of coping with real-life anxiety, its negative impacts extend beyond aversive feelings and involve disruptions in ongoing goal-directed behaviors and cognitive functioning. Critical examples of cognitive constructs affected by anxiety are cognitive flexibility and decision making. In particular, anxiety impedes the ability to shift flexibly between strategies in response to changes in task demands, as well as the ability to maintain a strategy in the presence of distractors. The brain region most critically involved in behavioral flexibility is the prefrontal cortex (PFC), but little is known about how anxiety impacts PFC encoding of internal and external events that are critical for flexible behavior. Here we review animal and human neurophysiological and neuroimaging studies implicating PFC neural processing in anxiety-induced deficits in cognitive flexibility. We then suggest experimental and analytical approaches for future studies to gain a better mechanistic understanding of impaired cognitive inflexibility in anxiety and related disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. 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.

  3. Role of the medial prefrontal cortex in coping and resilience.

    Science.gov (United States)

    Maier, Steven F; Watkins, Linda R

    2010-10-08

    The degree of behavioral control that an organism has over an aversive event is well known to modulate the behavioral and neurochemical consequences of exposure to the event. Here we review recent research that suggests that the experience of control over a potent stressor alters how the organism responds to future aversive events as well as to the stressor being controlled. More specifically, subjects that have experienced control show blunted behavioral and neurochemical responses to subsequent stressors occurring days to months later. Indeed, these subjects respond as if a later uncontrollable stressor is actually controllable. Further, we review research indicating that the stress resistance induced by control depends on control-induced activation of ventral medial prefrontal cortical (vmPFC) inhibitory control over brainstem and limbic structures. Furthermore, there appears to be plasticity in these circuits such that the experience of control alters the vmPFC in such a way that later uncontrollable stressors now activate the vmPFC circuitry, leading to inhibition of stress-responsive limbic and brainstem structures, i.e., stressor resistance. This controllability-induced proactive stressor resistance generalizes across very different stressors and may be involved in determining individual difference in reactions to traumatic events. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.

    Science.gov (United States)

    Bjorkquist, Olivia A; Olsen, Emily K; Nelson, Brady D; Herbener, Ellen S

    2016-08-01

    Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Prefrontal-amygdala fear networks come into focus

    Directory of Open Access Journals (Sweden)

    Maithe eArruda-Carvalho

    2015-10-01

    Full Text Available The ability to form associations between aversive threats and their predictors is fundamental to survival. However, fear and anxiety in excess are detrimental and are a hallmark of psychiatric diseases such as post-traumatic stress disorder (PTSD. PTSD symptomatology includes persistent and intrusive thoughts of an experienced trauma, suggesting an inability to downregulate fear when a corresponding threat has subsided. Convergent evidence from human and rodent studies supports a role for the medial prefrontal cortex (mPFC-amygdala network in both PTSD and the regulation of fear memory expression. In particular, current models stipulate that the prelimbic and infralimbic subdivisions of the rodent mPFC bidirectionally regulate fear expression via differential recruitment of amygdala neuronal subpopulations. However, an array of recent studies that employ new technical approaches has fundamentally challenged this interpretation. Here we explore how a new emphasis on the contribution of inhibitory neuronal populations, subcortical structures and the passage of time is reshaping our understanding of mPFC-amygdala circuits and their control over fear.

  6. Transient medial prefrontal perturbation reduces false memory formation.

    Science.gov (United States)

    Berkers, Ruud M W J; van der Linden, Marieke; de Almeida, Rafael F; Müller, Nils C J; Bovy, Leonore; Dresler, Martin; Morris, Richard G M; Fernández, Guillén

    2017-03-01

    Knowledge extracted across previous experiences, or schemas, benefit encoding and retention of congruent information. However, they can also reduce specificity and augment memory for semantically related, but false information. A demonstration of the latter is given by the Deese-Roediger-McDermott (DRM) paradigm, where the studying of words that fit a common semantic schema are found to induce false memories for words that are congruent with the given schema, but were not studied. The medial prefrontal cortex (mPFC) has been ascribed the function of leveraging prior knowledge to influence encoding and retrieval, based on imaging and patient studies. Here, we used transcranial magnetic stimulation (TMS) to transiently perturb ongoing mPFC processing immediately before participants performed the DRM-task. We observed the predicted reduction in false recall of critical lures after mPFC perturbation, compared to two control groups, whereas veridical recall and recognition memory performance remained similar across groups. These data provide initial causal evidence for a role of the mPFC in biasing the assimilation of new memories and their consolidation as a function of prior knowledge. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Rat prefrontal cortical neurons selectively code strategy switches.

    Science.gov (United States)

    Rich, Erin L; Shapiro, Matthew

    2009-06-03

    Multiple memory systems are distinguished by different sets of neuronal circuits and operating principles optimized to solve different problems across mammalian species (Tulving and Schacter, 1994). When a rat selects an arm in a plus maze, for example, the choice can be guided by distinct neural systems (White and Wise, 1999) that encode different relationships among perceived stimuli, actions, and reward. Thus, egocentric or stimulus-response associations require striatal circuits, whereas spatial or episodic learning requires hippocampal circuits (Packard et al., 1989). Although these memory systems function in parallel (Packard and McGaugh, 1996), they can also interact competitively or synergistically (Kim and Ragozzino, 2005). The neuronal mechanisms that coordinate these multiple memory systems are not fully known, but converging evidence suggests that the prefrontal cortex (PFC) is central. The PFC is crucial for abstract, rule-guided behavior in primates and for switching rapidly between memory strategies in rats. We now report that rat medial PFC neuronal activity predicts switching between hippocampus- and caudate-dependent memory strategies. Prelimbic (PL) and infralimbic (IL) neuronal activity changed as rats switched memory strategies even as the rats performed identical behaviors but did not change when rats learned new contingencies using the same strategy. PL dynamics anticipated learning performance whereas IL lagged, suggesting that the two regions help initiate and establish new strategies, respectively. These neuronal dynamics suggest that the PFC contributes to the coordination of memory strategies by integrating the predictive relationships among stimuli, actions, and reward.

  8. prefrontal como mecanismo putativo del cambio en psicoterapia

    Directory of Open Access Journals (Sweden)

    Jaime Silva C.

    2005-01-01

    Full Text Available La corteza prefrontal (CPF es definida como la región cerebral cortical que se conecta recíprocamente con el núcleo dorsolateral del tálamo. La visión tradicional en las ciencias del comportamiento atribuye a la CPF un papel en la organización temporal de la conducta. Adicionalmente, estudios convergentes en el campo de la neurociencia afectiva han revelado el papel fundamental que juega la CPF en la determinación del estilo afectivo y en especial de la regulación emocional. El estilo afectivo involucra las diferencias individuales en diferentes parámetros de la reactividad afectiva y el estado de ánimo disposicional (por ejemplo, amplitud de la respuesta emocional, tiempo de recuperación, etc.. Dado que prácticamente todas las alteraciones psicopatológicas incluyen un trastorno en alguno de esos parámetros, proponemos que la modulación de la actividad de la CPF es una variable fundamental del cambio en psicoterapia. Presentamos nuestro modelo putativo, el cual se fundamenta en el control cognitivo en cascada de la CPF. Específicamente, proponemos que la regulación emocional ocurre asociada a la activación de la CPF lateral en un sentido rostralcaudal, donde zonas rostrales involucran formas complejas de control afectivo.

  9. Basic mathematical rules are encoded by primate prefrontal cortex neurons.

    Science.gov (United States)

    Bongard, Sylvia; Nieder, Andreas

    2010-02-02

    Mathematics is based on highly abstract principles, or rules, of how to structure, process, and evaluate numerical information. If and how mathematical rules can be represented by single neurons, however, has remained elusive. We therefore recorded the activity of individual prefrontal cortex (PFC) neurons in rhesus monkeys required to switch flexibly between "greater than" and "less than" rules. The monkeys performed this task with different numerical quantities and generalized to set sizes that had not been presented previously, indicating that they had learned an abstract mathematical principle. The most prevalent activity recorded from randomly selected PFC neurons reflected the mathematical rules; purely sensory- and memory-related activity was almost absent. These data show that single PFC neurons have the capacity to represent flexible operations on most abstract numerical quantities. Our findings support PFC network models implementing specific "rule-coding" units that control the flow of information between segregated input, memory, and output layers. We speculate that these neuronal circuits in the monkey lateral PFC could readily have been adopted in the course of primate evolution for syntactic processing of numbers in formalized mathematical systems.

  10. Gelastic seizures with dancing arising from the anterior prefrontal cortex.

    Science.gov (United States)

    Neilson, John; Snyder, Tom; Pugh, Jeff; Wheatley, Matt; Tang-Wai, Richard

    2014-06-01

    This case report provides insight into the function of the anterior prefrontal cortex (aPFC), specifically Brodmann Area 10 (BA10), and its interconnectivity. We present a 10-year-old patient with lesional epilepsy and ictal onset, localised to BA10 in the aPFC. Thirty-four seizures were recorded. All seizures involved a demonstration of elation with laughter that was associated with a variety of different patterns of complex motor behaviour that included performing specific celebratory movements and acting out a Michael Jackson dance move. Electrographically, the seizures were all stereotyped and arose from the right frontal region, followed by a distinct left temporal ictal rhythm that corresponded with the onset of the behaviours. The lesion in the right aPFC was identified as a mixed lesion with both dysembryoplastic neuroepithelial tumour cells and type II cortical dysplasia. The electrographic analysis and unique seizure semiology suggest a connection between the aPFC and the contralateral temporal lobe. This neural pathway appears to be involved in the activation of previously formed procedural memories, creating an intensely positive emotional experience.

  11. Counteracting Implicit Conflicts by Electrical Inhibition of the Prefrontal Cortex.

    Science.gov (United States)

    Schroeder, Philipp Alexander; Pfister, Roland; Kunde, Wilfried; Nuerk, Hans-Christoph; Plewnia, Christian

    2016-11-01

    Cognitive conflicts and distractions by task-irrelevant information often counteract effective and goal-directed behaviors. In some cases, conflicting information can even emerge implicitly, without an overt distractor, by the automatic activation of mental representations. For instance, during number processing, magnitude information automatically elicits spatial associations resembling a mental number line. This spatial-numerical association of response codes (SNARC) effect can modulate cognitive-behavioral performance but is also highly flexible and context-dependent, which points toward a critical involvement of working memory functions. Transcranial direct current stimulation to the PFC, in turn, has been effective in modulating working memory-related cognitive performance. In a series of experiments, we here demonstrate that decreasing activity of the left PFC by cathodal transcranial direct current stimulation consistently and specifically eliminates implicit cognitive conflicts based on the SNARC effect, but explicit conflicts based on visuospatial distraction remain unaffected. This dissociation is polarity-specific and appears unrelated to functional magnitude processing as classified by regular numerical distance effects. These data demonstrate a causal involvement of the left PFC in implicit cognitive conflicts based on the automatic activation of spatial-numerical processing. Corroborating the critical interaction of brain stimulation and neurocognitive functions, our findings suggest that distraction from goal-directed behavior by automatic activation of implicit, task-irrelevant information can be blocked by the inhibition of prefrontal activity.

  12. Unconscious errors enhance prefrontal-occipital oscillatory synchrony

    Directory of Open Access Journals (Sweden)

    Michael X Cohen

    2009-11-01

    Full Text Available The medial prefrontal cortex (MFC is critical for our ability to learn from previous mistakes. Here we provide evidence that neurophysiological oscillatory long-range synchrony is a mechanism of post-error adaptation that occurs even without conscious awareness of the error. During a visually signaled Go/No-Go task in which half of the No-Go cues were masked and thus not consciously perceived, response errors enhanced tonic (i.e., over 1-2 seconds oscillatory synchrony between MFC and occipital cortex leading up to and during the subsequent trial. Spectral Granger causality analyses demonstrated that MFC >  occipital cortex directional synchrony was enhanced during trials following both conscious and unconscious errors, whereas transient stimulus-induced occipital >  MFC directional synchrony was independent of errors in the previous trial. Further, the strength of pre-trial MFC-occipital synchrony predicted individual differences in task performance. Together, these findings suggest that synchronous neurophysiological oscillations are a plausible mechanism of MFC-driven cognitive control that is independent of conscious awareness.

  13. A psychophysiological investigation of moral judgment after ventromedial prefrontal damage.

    Science.gov (United States)

    Moretto, Giovanna; Làdavas, Elisabetta; Mattioli, Flavia; di Pellegrino, Giuseppe

    2010-08-01

    Converging evidence suggests that emotion processing mediated by ventromedial prefrontal cortex (vmPFC) is necessary to prevent personal moral violations. In moral dilemmas, for example, patients with lesions in vmPFC are more willing than normal controls to approve harmful actions that maximize good consequences (e.g., utilitarian moral judgments). Yet, none of the existing studies has measured subjects' emotional responses while they considered moral dilemmas. Therefore, a direct link between emotion processing and moral judgment is still lacking. Here, vmPFC patients and control participants considered moral dilemmas while skin conductance response (SCR) was measured as a somatic index of affective state. Replicating previous evidence, vmPFC patients approved more personal moral violations than did controls. Critically, we found that, unlike control participants, vmPFC patients failed to generate SCRs before endorsing personal moral violations. In addition, such anticipatory SCRs correlated negatively with the frequency of utilitarian judgments in normal participants. These findings provide direct support to the hypothesis that the vmPFC promotes moral behavior by mediating the anticipation of the emotional consequences of personal moral violations.

  14. Scopolamine Impairs Appetitive But Not Aversive Trace Conditioning: Role of the Medial Prefrontal Cortex.

    Science.gov (United States)

    Pezze, Marie-Astrid; Marshall, Hayley J; Cassaday, Helen J

    2017-06-28

    The muscarinic acetylcholine receptor is an important modulator of medial prefrontal cortex (mPFC) functions, such as the working memory required to bridge a trace interval in associative leaning. Aversive and appetitive trace conditioning procedures were used to examine the effects of scopolamine (0.1 and 0.5 mg/kg, i.p.) in male rats. Follow-up experiments tested the effects of microinfusion of 0.15 μg of scopolamine (0.075 μg of in 0.5 μl/side) in infralimbic (IL) versus prelimbic regions of rat mPFC, in appetitive trace and locomotor activity (LMA) procedures. Systemic scopolamine was without effect in an aversive trace conditioning procedure, but impaired appetitive conditioning at a 2 s trace interval. This effect was demonstrated as reduced responding during presentations of the conditioned stimulus (CS) and during the interstimulus interval (ISI). There was no such effect on responding during food (unconditioned stimulus, US) responding or in the intertrial interval (ITI). In contrast, systemic scopolamine dose-relatedly increased LMA. Trace conditioning was similarly impaired at the 2 s trace (shown as reduced responding to the CS and during the ISI, but not during US presentations or in the ITI) after infusion in mPFC, whereas LMA was increased (after infusion in IL only). Therefore, our results point to the importance of cholinergic modulation in mPFC for trace conditioning and show that the observed effects cannot be attributed to reduced activity.SIGNIFICANCE STATEMENT Events are very often separated in time, in which case working memory is necessary to condition their association in "trace conditioning." The present study used conditioning variants motivated aversively with foot shock and appetitively with food. The drug scopolamine was used to block muscarinic acetylcholine receptors involved in working memory. The results show that reduced cholinergic transmission in medial prefrontal cortex (mPFC) impaired appetitive trace conditioning at a 2 s

  15. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

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

    Science.gov (United States)

    Lindsay, Grace W; Rigotti, Mattia; Warden, Melissa R; Miller, Earl K; Fusi, Stefano

    2017-11-08

    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 ("mixed

  17. Lesions to the left lateral prefrontal cortex impair decision threshold adjustment for lexical selection.

    Science.gov (United States)

    Anders, Royce; Riès, Stéphanie; Van Maanen, Leendert; Alario, F-Xavier

    Patients with lesions in the left prefrontal cortex (PFC) have been shown to be impaired in lexical selection, especially when interference between semantically related alternatives is increased. To more deeply investigate which computational mechanisms may be impaired following left PFC damage due to stroke, a psychometric modelling approach is employed in which we assess the cognitive parameters of the patients from an evidence accumulation (sequential information sampling) modelling of their response data. We also compare the results to healthy speakers. Analysis of the cognitive parameters indicates an impairment of the PFC patients to appropriately adjust their decision threshold, in order to handle the increased item difficulty that is introduced by semantic interference. Also, the modelling contributes to other topics in psycholinguistic theory, in which specific effects are observed on the cognitive parameters according to item familiarization, and the opposing effects of priming (lower threshold) and semantic interference (lower drift) which are found to depend on repetition. These results are developed for the blocked-cyclic picture naming paradigm, in which pictures are presented within semantically homogeneous (HOM) or heterogeneous (HET) blocks, and are repeated several times per block. Overall, the results are in agreement with a role of the left PFC in adjusting the decision threshold for lexical selection in language production.

  18. Two Days' Sleep Debt Causes Mood Decline During Resting State Via Diminished Amygdala-Prefrontal Connectivity.

    Science.gov (United States)

    Motomura, Yuki; Katsunuma, Ruri; Yoshimura, Michitaka; Mishima, Kazuo

    2017-10-01

    Sleep debt (SD) has been suggested to evoke emotional instability by diminishing the suppression of the amygdala by the medial prefrontal cortex (MPFC). Here, we investigated how short-term SD affects resting-state functional connectivity between the amygdala and MPFC, self-reported mood, and sleep parameters. Eighteen healthy adult men aged 29 ± 8.24 years participated in a 2-day sleep control session (SC; time in bed [TIB], 9 hours) and 2-day SD session (TIB, 3 hours). On day 2 of each session, resting-state functional magnetic resonance imaging was performed, followed immediately by measuring self-reported mood on the State-Trait Anxiety Inventory-State subscale (STAI-S). STAI-S score was significantly increased, and functional connectivity between the amygdala and MPFC was significantly decreased in SD compared with SC. Significant correlations were observed between reduced rapid eye movement (REM) sleep and reduced left amygdala-MPFC functional connectivity (FCL_amg-MPFC) and between reduced FCL_amg-MPFC and increased STAI-S score in SD compared with SC. These findings suggest that reduced MPFC functional connectivity of amygdala activity is involved in mood deterioration under SD, and that REM sleep reduction is involved in functional changes in the corresponding brain regions. Having adequate REM sleep may be important for mental health maintenance.

  19. Dopamine D2 Receptors Enhance Population Dynamics in Primate Prefrontal Working Memory Circuits.

    Science.gov (United States)

    Ott, Torben; Nieder, Andreas

    2017-09-01

    Working memory is associated with persistent activity in the prefrontal cortex (PFC). The neuromodulator dopamine, which is released by midbrain neurons projecting into the frontal lobe, influences PFC neurons and networks via the dopamine D1 (D1R) and the D2 receptor (D2R) families. Although behavioral, clinical and computational evidence suggest an involvement of D2Rs in working memory, a neuronal explanation is missing. We report an enhancement of persistent working memory responses of PFC neurons after iontophoretically stimulating D2Rs in monkeys memorizing the number of items in a display. D2R activation improved working memory representation at the population level and increased population dynamics during the transition from visual to mnemonic representations. Computational modeling suggests that D2Rs act by modulating interneuron-to-pyramidal signaling. By increasing the population's response dynamics, D2Rs might put PFC networks in a more flexible state and enhance the neurons' working memory coding, thereby controlling dynamic cognitive control. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. The NOS1 variant rs6490121 is associated with variation in prefrontal function and grey matter density in healthy individuals.

    LENUS (Irish Health Repository)

    Rose, Emma J

    2012-03-01

    A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the \\'G\\' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk \\'A\\' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in \\'G\\' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and\\/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

  1. Prefrontal EEG alpha asymmetry changes while observing disaster happening to other people: cardiac correlates and prediction of emotional impact.

    Science.gov (United States)

    Papousek, Ilona; Weiss, Elisabeth M; Schulter, Günter; Fink, Andreas; Reiser, Eva M; Lackner, Helmut K

    2014-12-01

    Changes of EEG alpha asymmetry in terms of increased right versus left sided activity in prefrontal cortex are considered to index activation of the withdrawal/avoidance motivational system. The present study aimed to add evidence of the validity of individual differences in the EEG alpha asymmetry response and their relevance regarding the impact of emotional events. The magnitude of the EEG alpha asymmetry response while watching a film consisting of scenes of real injury and death correlated with components of transient cardiac responses to sudden horrifying events happening to persons in the film which index withdrawal/avoidance motivation and heightened attention and perceptual intake. Additionally, it predicted greater mood deterioration following the film and film-related intrusive memories and avoidance over the following week. The study provides further evidence for prefrontal EEG alpha asymmetry changes in response to relevant stimuli reflecting an individual's sensitivity to negative social-emotional cues encountered in everyday life. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series.

    Science.gov (United States)

    Jay, Emma-Louise; Nestler, Steffen; Sierra, Mauricio; McClelland, Jessica; Kekic, Maria; David, Anthony S

    2016-06-30

    Case reports and an open trial have reported promising responses to repetitive transcranial magnetic stimulation (rTMS) to prefrontal and temporo-parietal sites in patients with depersonalization disorder (DPD). We recently showed that a single session of rTMS to the ventrolateral prefrontal cortex (VLPFC) was associated with a reduction in symptoms and increase in physiological arousal. Seven patients with medication-resistant DSM-IV DPD received up to 20 sessions of right-sided rTMS to the VLPFC for 10 weeks. Stimulation was guided using neuronavigation software based on participants' individual structural MRIs, and delivered at 110% of resting motor threshold. A session consisted of 1Hz repetitive TMS for 15min. The primary outcome measure was reduction in depersonalization symptoms on the Cambridge Depersonalization Scale (CDS). Secondary outcomes included scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). 20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44% (range 2-83.5%). Two patients could be classified as "full responders", four as "partial" and one a non-responder. Response usually occurred within the first 6 sessions. There were no significant adverse events. A randomized controlled clinical trial of VLPFC rTMS for DPD is warranted. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Ventrolateral prefrontal activation during a N-back task assessed with multichannel functional near-infrared spectroscopy

    Science.gov (United States)

    Zhou, Yuan; Zhu, Ye; Jiang, Tianzi

    2007-05-01

    Functional near-infrared spectroscopy (fNIRS) has been used to investigate the changes in the concentration of oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin in brain issue during several cognitive tasks. In the present study, by means of multichannel dual wavelength light-emitting diode continuous-wave (CW) NIRS, we investigated the blood oxygenation changes of prefrontal cortex in 18 healthy subjects while performing a verbal n-back task (0-back and 2-back), which has been rarely investigated by fNIRS. Compared to the 0-back task (control task), we found a significant increase of O2Hb and total amount of hemoglobin (THb) in left and right ventrolateral prefrontal cortex (VLPFC) during the execution of the 2-back task compared to the 0-back task (pdominance. In addition, the effects of gender and its interaction with task performance on O2Hb concentration change were suggested in the present study. Our findings not only confirm that multichannel fNIRS is suitable to detect spatially specific activation during the performance of cognitive tasks; but also suggest that it should be cautious of gender-dependent difference in cerebral activation when interpreting the fNIRS data during cognitive tasks.

  4. 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.

  5. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  6. Working memory performance correlates with prefrontal-hippocampal theta interactions but not with prefrontal neuron firing rates

    Directory of Open Access Journals (Sweden)

    James M Hyman

    2010-03-01

    Full Text Available Performance of memory tasks is impaired by lesions to either the medial prefrontal cortex (mPFC or the hippocampus (HPC; although how these two areas contribute to successful performance is not well understood. mPFC unit activity is temporally affected by hippocampal theta oscillations, with almost half the mPFC population entrained to theta in behaving animals, pointing to theta interactions as the mechanism enabling collaborations between these two areas. mPFC neurons respond to sensory stimuli and responses in working memory tasks, though the function of these correlated firing rate changes remains unclear because similar responses are reported during mPFC dependent and independent tasks. Using a DNMS task we compared error trials vs. correct trials and found almost all mPFC cells fired at similar rates during both error and correct trials (92%, however theta-entrainment of mPFC neurons declined during error performance as only 17% of cells were theta-entrained (during correct trials 46% of the population was theta-entrained. Across the population, error and correct trials did not differ in firing rate, but theta-entrainment was impaired. Periods of theta-entrainment and firing rate changes appeared to be independent variables, and only theta-entrainment was correlated with successful performance, indicating mPFC-HPC theta range interactions are the key to successful DNMS performance.

  7. Effect of novel atypical antipsychotic, blonanserin, on extracellular neurotransmitter level in rat prefrontal cortex.

    Science.gov (United States)

    Ohoyama, Keiko; Yamamura, Satoshi; Hamaguchi, Tatsuya; Nakagawa, Masanori; Motomura, Eishi; Shiroyama, Takashi; Tanii, Hisashi; Okada, Motohiro

    2011-02-25

    To clarify the mechanisms of action of blonanserin, an atypical antipsychotic drug, we studied the effects of systemic administration of blonanserin and risperidone on extracellular levels of norepinephrine, dopamine, serotonin, GABA and glutamate in the medial prefrontal cortex using microdialysis, and neuronal firing in the ventral tegmental area, locus coeruleus, dorsal raphe nucleus and mediodorsal thalamic nucleus using radiotelemetry. The binding affinities of blonanserin to D(2) and 5-HT(2A) receptors in the rat brain were confirmed and found to be similar. Blonanserin transiently increased neuronal firing in locus coeruleus and ventral tegmental area but not in dorsal raphe nucleus or mediodorsal thalamic nucleus, whereas risperidone increased the firing in locus coeruleus, ventral tegmental area and dorsal raphe nucleus but not in mediodorsal thalamic nucleus. Blonanserin persistently increased frontal extracellular levels of norepinephrine and dopamine but not serotonin, GABA or glutamate, whereas risperidone persistently increased those of norepinephrine, dopamine and serotonin but not GABA or glutamate. These results suggest a pharmacological correlation between the stimulatory effects of these antipsychotics on frontal monoamine release and neuronal activity in monoaminergic nuclei. Inhibition of the α(2) adrenoceptor increased extracellular monoamine levels and enhanced blonanserin-induced increase in extracellular serotonin level. These results indicated that the combination of antagonism of D(2) and 5-HT(2A) receptors contribute to the rise in extracellular levels of norepinephrine and dopamine, and that α(2) adrenoceptors play important roles in frontal serotonin release. They also suggest that blonanserin-induced activation of monoaminergic transmission could be, at least partially, involved in atypical antipsychotic properties of blonanserin. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Prefrontal lobotomy on Evita was done for behavior/personality modification, not just for pain control.

    Science.gov (United States)

    Nijensohn, Daniel E

    2015-07-01

    Eva Perón, best known as Evita, underwent a prefrontal lobotomy in 1952. Although the procedure was said to have been performed to relieve the pain of metastatic cancer, the author carried out a search for evidence that suggests that the procedure was prescribed to decrease violence and to modify Evita's behavior and personality, and not just for pain control. To further elucidate the circumstances surrounding the treatment of this well-known historic figure, the author reviewed the development of the procedure known as prefrontal lobotomy and its three main indications: management of psychiatric illness, control of intractable pain from terminal cancer, and mind control and behavior/personality modification. The role of pioneering neurosurgeons in the development of prefrontal lobotomy, particularly in Connecticut and at Yale University, was also studied, and the political and historical conditions in Argentina in 1952 and to the present were analyzed. Evita was the wife of Juan Perón, who was the supreme leader of the Peronist party as well as president of Argentina. In 1952, however, the Peronist government in Argentina was bicephalic because Evita led the left wing of the party and ran the Female Peronist Party and the Eva Perón Foundation. She was followed by a group of hardcore loyalists interested in accelerating the revolution. Evita was also suffering from metastatic cervical cancer, and her illness increased her anxiety and moved her to purchase weapons to start training workers' militias. Although the apparent purpose was to fight her husband's enemies, this was done without his knowledge. She delivered fiery political speeches and wrote incendiary documents that would have led to a fierce clash in the country at that time. Notwithstanding the disreputable connotation of conspiracy theories, evidence was found of a potentially sinister political conspiracy, led by General Perón, to quiet down his wife Evita and modify her behavior/personality to

  9. Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex.

    Directory of Open Access Journals (Sweden)

    Stefanos Stefanou - Stamatiadis

    2014-03-01

    Full Text Available The application of new experimental techniques in vivo has shed light on the wiring diagram of cortical networks, revealing the highly non-random connectivity of pyramidal neurons. This structured connectivity is characterized by distance-dependent formation of neuronal clusters and over-represented structural ‘motifs’ (Perin 2011, Ko 2013. In the prefrontal cortex (PFC in particular, pyramidal neurons were shown to form hyper-clusters, compared to other sensory regions. Yet, very little is known about the functional properties of these microcircuits and their role in Persistent Activity (PA, a well known function of the PFC. PA is the spiking activity that persists beyond the stimulus presentation and is considered to be the cellular correlate of working memory. Although, PA was traditionally assumed to emerge in large scale networks, recent in vivo data in the PFC suggest that small microcircuits mediate it