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Sample records for prefrontal cortex modulates

  1. Cholinergic modulation of working memory activity in primate prefrontal cortex.

    PubMed

    Zhou, Xin; Qi, Xue-Lian; Douglas, Kristy; Palaninathan, Kathini; Kang, Hyun Sug; Buccafusco, Jerry J; Blake, David T; Constantinidis, Christos

    2011-11-01

    The prefrontal cortex, a cortical area essential for working memory and higher cognitive functions, is modulated by a number of neurotransmitter systems, including acetylcholine; however, the impact of cholinergic transmission on prefrontal activity is not well understood. We relied on systemic administration of a muscarinic receptor antagonist, scopolamine, to investigate the role of acetylcholine on primate prefrontal neuronal activity during execution of working memory tasks and recorded neuronal activity with chronic electrode arrays and single electrodes. Our results indicated a dose-dependent decrease in behavioral performance after scopolamine administration in all the working memory tasks we tested. The effect could not be accounted for by deficits in visual processing, eye movement responses, or attention, because the animals performed a visually guided saccade task virtually error free, and errors to distracting stimuli were not increased. Performance degradation under scopolamine was accompanied by decreased firing rate of the same cortical sites during the delay period of the task and decreased selectivity for the spatial location of the stimuli. These results demonstrate that muscarinic blockade impairs performance in working memory tasks and prefrontal activity mediating working memory.

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

    PubMed

    Stollstorff, Melanie; Vartanian, Oshin; Goel, Vinod

    2012-01-05

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

  3. Prefrontal cortical modulation of acetylcholine release in posterior parietal cortex.

    PubMed

    Nelson, C L; Sarter, M; Bruno, J P

    2005-01-01

    Attentional processing is a crucial early stage in cognition and is subject to "top-down" regulation by prefrontal cortex (PFC). Top-down regulation involves modification of input processing in cortical and subcortical areas, including the posterior parietal cortex (PPC). Cortical cholinergic inputs, originating from the basal forebrain cholinergic system, have been demonstrated to mediate important aspects of attentional processing. The present study investigated the ability of cholinergic and glutamatergic transmission within PFC to regulate acetylcholine (ACh) release in PPC. The first set of experiments demonstrated increases in ACh efflux in PPC following AMPA administration into the PFC. These increases were antagonized by co-administration of the AMPA receptor antagonist DNQX into the PFC. The second set of experiments demonstrated that administration of carbachol, but not nicotine, into the PFC also increased ACh efflux in PPC. The effects of carbachol were attenuated by co-administration (into PFC) of a muscarinic antagonist (atropine) and partially attenuated by the nicotine antagonist mecamylamine and DNQX. Perfusion of carbachol, nicotine, or AMPA into the PPC did not affect PFC ACh efflux, suggesting that these cortical interactions are not bi-directional. These studies demonstrate the capacity of the PFC to regulate ACh release in the PPC via glutamatergic and cholinergic prefrontal mechanisms. Prefrontal regulation of ACh release elsewhere in the cortex is hypothesized to contribute to the cognitive optimization of input processing.

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

    PubMed Central

    Richard, Jocelyn M.; Berridge, Kent. C

    2012-01-01

    Background Corticolimbic circuits, including direct projections from prefrontal cortex to nucleus accumbens (NAc), permit “top-down” control of intense motivations generated by subcortical circuits. In rats, localized disruptions of glutamate signaling within medial shell of NAc generate desire or dread, anatomically organized along a rostrocaudal gradient analogous to a limbic “keyboard”. At rostral locations in shell these disruptions generate appetitive eating, but at caudal locations the disruptions generate progressively fearful behaviors (distress vocalizations, escape attempts and antipredator reactions). Here we asked whether medial prefrontal cortex can modulate intense motivations generated by subcortical NAc disruptions. Methods We used simultaneous microinjections in medial prefrontal cortex regions and in NAc shell to examine whether the desire or dread generated by NAc shell disruptions is modulated by activation/inhibition of three specific regions of prefrontal cortex: medial orbitofrontal cortex, infralimbic cortex (homologous to area 25 or subgenual anterior cingulate in the human), or prelimbic cortex (midventral anterior cingulate). Results We found that activation of medial orbitofrontal cortex biased intense bivalent motivation in an appetitive direction by amplifying generation of eating behavior by middle to caudal NAc disruptions, without altering fear. In contrast, activation of infralimbic prefrontal cortex powerfully and generally suppressed both appetitive eating and fearful behaviors generated by NAc shell disruptions. Conclusions These results suggest that corticolimbic projections from discrete prefrontal regions can either bias motivational valence or generally suppress subcortically-generated intense motivations of desire or fear. PMID:22981656

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

    PubMed

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

    2014-10-15

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

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

    PubMed

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

    2016-06-15

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

  7. Task-relevant modulation of primary somatosensory cortex suggests a prefrontal-cortical sensory gating system.

    PubMed

    Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael

    2005-08-01

    Increasing evidence suggests that somatosensory information is modulated cortically for task-specific sensory inflow: Several studies report short-term adaptation of representational maps in primary somatosensory cortex (SI) due to attention or induced by task-related motor activity such as handwriting. Recently, it has been hypothesized that the frontal or prefrontal cortex may modulate SI. In order to test this hypothesis, we studied the functional organization of SI while subjects performed the Tower of Hanoi task. This task is known to be related to activation of frontal or prefrontal areas. The functional organization of SI while performing the Tower of Hanoi task was compared to the organization of SI during performing the same movements but without the Tower of Hanoi task and with rest. Topography of SI was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digits (D5). Performing the Tower of Hanoi task was accompanied by plastic changes in SI as indicated by significant shifts in the cortical representations of D1 and D5: They moved further apart during the Tower of Hanoi task compared to the control task containing the same movements but without the cognitive characteristic. Thus, we conclude that SI maps undergo dynamic modulation depending on motor tasks with different cognitive demands. The results suggest that this short-term plasticity may be regulated by a prefrontal-cortical sensory gating system.

  8. Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

    PubMed

    Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

    2015-01-01

    Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

  9. Reward Sensitivity Modulates Brain Activity in the Prefrontal Cortex, ACC and Striatum during Task Switching

    PubMed Central

    Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C.; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

    2015-01-01

    Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies. PMID:25875640

  10. Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.

    PubMed

    Murakami, Gen; Nakamura, Masato; Takita, Masatoshi; Ishida, Yasushi; Ueki, Takatoshi; Nakahara, Daiichiro

    2015-11-01

    Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1 min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats.

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

    PubMed

    Conson, Massimiliano; Errico, Domenico; Mazzarella, Elisabetta; Giordano, Marianna; Grossi, Dario; Trojano, Luigi

    2015-01-01

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

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

    PubMed Central

    Conson, Massimiliano; Errico, Domenico; Mazzarella, Elisabetta; Giordano, Marianna; Grossi, Dario; Trojano, Luigi

    2015-01-01

    Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person’s visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants’ tendency to adopt another’s point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males’ responses to threatening faces whereas it interferes with the ability to adopt another’s viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing. PMID:25951227

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

    PubMed Central

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

    2011-01-01

    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. PMID:21646526

  14. Listen to Yourself: The Medial Prefrontal Cortex Modulates Auditory Alpha Power During Speech Preparation.

    PubMed

    Müller, Nadia; Leske, Sabine; Hartmann, Thomas; Szebényi, Szabolcs; Weisz, Nathan

    2015-11-01

    How do we process stimuli that stem from the external world and stimuli that are self-generated? In the case of voice perception it has been shown that evoked activity elicited by self-generated sounds is suppressed compared with the same sounds played-back externally. We here wanted to reveal whether neural excitability of the auditory cortex-putatively reflected in local alpha band power--is modulated already prior to speech onset, and which brain regions may mediate such a top-down preparatory response. In the left auditory cortex we show that the typical alpha suppression found when participants prepare to listen disappears when participants expect a self-spoken sound. This suggests an inhibitory adjustment of auditory cortical activity already before sound onset. As a second main finding we demonstrate that the medial prefrontal cortex, a region known for self-referential processes, mediates these condition-specific alpha power modulations. This provides crucial insights into how higher-order regions prepare the auditory cortex for the processing of self-generated sounds. Furthermore, the mechanism outlined could provide further explanations to self-referential phenomena, such as "tickling yourself". Finally, it has implications for the so-far unsolved question of how auditory alpha power is mediated by higher-order regions in a more general sense.

  15. Inhibitory modulation of medial prefrontal cortical activation on lateral orbitofrontal cortex-amygdala information flow.

    PubMed

    Chang, Chun-Hui; Ho, Ta-Wen

    2017-09-01

    The basolateral complex of the amygdala (BLA) receives input from the lateral orbitofrontal cortex (lOFC) for cue-outcome contingencies and the medial prefrontal cortex (mPFC) for emotion control. Here we examined how the mPFC modulates lOFC-BLA information flow. We found that the majority of BLA neurons responsive to lOFC stimulation were also responsive to mPFC stimulation. Activation of the mPFC exerted an inhibitory modulation of the lOFC-BLA pathway, which was reversed with intra-amygdala blockade of GABAergic receptors. mPFC tetanus potentiated the lOFC-BLA pathway, but did not alter its inhibitory modulatory gating. These results show that the mPFC potently inhibits lOFC drive of the BLA in a GABA-dependent manner, which is informative in understanding the normal and potential pathophysiological state of emotion and contingency associations in regulating behaviour. Several neocortical projections converge onto the basolateral complex of the amygdala (BLA), including the lateral orbitofrontal cortex (lOFC) and the medial prefrontal cortex (mPFC). Lateral orbitofrontal input to the BLA is important for cue-outcome contingencies, while medial prefrontal input is essential for emotion control. In this study, we examined how the mPFC, specifically the infralimbic division of the mPFC, modulates lOFC-BLA information flow, using combined in vivo extracellular single-unit recordings and pharmacological manipulations in anaesthetized rats. We found that the majority (over 95%) of BLA neurons that responded to lOFC stimulation also responded to mPFC stimulation. Compared to basal condition, pharmacological (N-methyl-d-aspartate) or electrical activation of the mPFC exerted an inhibitory modulation of the lOFC-BLA pathway, which was reversed with intra-amygdala blockade of GABAergic receptors with combined GABAA and GABAB antagonists (bicuculline and saclofen). Moreover, mPFC tetanus potentiated the lOFC-BLA pathway, but mPFC tetanus or low-frequency stimulation did

  16. Executive control over cognition: stronger and earlier rule-based modulation of spatial category signals in prefrontal cortex relative to parietal cortex.

    PubMed

    Goodwin, Shikha J; Blackman, Rachael K; Sakellaridi, Sofia; Chafee, Matthew V

    2012-03-07

    Human cognition is characterized by flexibility, the ability to select not only which action but which cognitive process to engage to best achieve the current behavioral objective. The ability to tailor information processing in the brain to rules, goals, or context is typically referred to as executive control, and although there is consensus that prefrontal cortex is importantly involved, at present we have an incomplete understanding of how computational flexibility is implemented at the level of prefrontal neurons and networks. To better understand the neural mechanisms of computational flexibility, we simultaneously recorded the electrical activity of groups of single neurons within prefrontal and posterior parietal cortex of monkeys performing a task that required executive control of spatial cognitive processing. In this task, monkeys applied different spatial categorization rules to reassign the same set of visual stimuli to alternative categories on a trial-by-trial basis. We found that single neurons were activated to represent spatially defined categories in a manner that was rule dependent, providing a physiological signature of a cognitive process that was implemented under executive control. We found also that neural signals coding rule-dependent categories were distributed between the parietal and prefrontal cortex--however, not equally. Rule-dependent category signals were stronger, more powerfully modulated by the rule, and earlier to emerge in prefrontal cortex relative to parietal cortex. This suggests that prefrontal cortex may initiate the switch in neural representation at a network level that is important for computational flexibility.

  17. Selective Modulation of the Pupil Light Reflex by Microstimulation of Prefrontal Cortex.

    PubMed

    Ebitz, R Becket; Moore, Tirin

    2017-05-10

    The prefrontal cortex (PFC) is thought to flexibly regulate sensorimotor responses, perhaps through modulating activity in other circuits. However, the scope of that control remains unknown: it remains unclear whether the PFC can modulate basic reflexes. One canonical example of a central reflex is the pupil light reflex (PLR): the automatic constriction of the pupil in response to luminance increments. Unlike pupil size, which depends on the interaction of multiple physiological and neuromodulatory influences, the PLR reflects the action of a simple brainstem circuit. However, emerging behavioral evidence suggests that the PLR may be modulated by cognitive processes. Although the neural basis of these modulations remains unknown, one possible source is the PFC, particularly the frontal eye field (FEF), an area of the PFC implicated in the control of attention. We show that microstimulation of the rhesus macaque FEF alters the magnitude of the PLR in a spatially specific manner. FEF microstimulation enhanced the PLR to probes presented within the stimulated visual field, but suppressed the PLR to probes at nonoverlapping locations. The spatial specificity of this effect parallels the effect of FEF stimulation on attention and suggests that FEF is capable of modulating visuomotor transformations performed at a lower level than was previously known. These results provide evidence of the selective regulation of a basic brainstem reflex by the PFC.SIGNIFICANCE STATEMENT The pupil light reflex (PLR) is our brain's first and most fundamental mechanism for light adaptation. Although it is often described in textbooks as being an immutable reflex, converging evidence suggests that the magnitude of the PLR is modulated by cognitive factors. The neural bases of these modulations are unknown. Here, we report that microstimulation in the prefrontal cortex (PFC) modulates the gain of the PLR, changing how a simple reflex circuit responds to physically identical stimuli. These

  18. Neuropsychology of prefrontal cortex

    PubMed Central

    Siddiqui, Shazia Veqar; Chatterjee, Ushri; Kumar, Devvarta; Siddiqui, Aleem; Goyal, Nishant

    2008-01-01

    The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different functional operations within the PFC. The specification of the component ‘executive’ processes and their localization to particular regions of PFC have been implicated in a wide variety of psychiatric disorders. PMID:19742233

  19. Executive Control Over Cognition: Stronger and Earlier Rule-Based Modulation of Spatial Category Signals in Prefrontal Cortex Relative to Parietal Cortex

    PubMed Central

    Goodwin, Shikha J.; Blackman, Rachael K.; Sakellaridi, Sofia

    2012-01-01

    Human cognition is characterized by flexibility, the ability to select not only which action but which cognitive process to engage to best achieve the current behavioral objective. The ability to tailor information processing in the brain to rules, goals, or context is typically referred to as executive control, and although there is consensus that prefrontal cortex is importantly involved, at present we have an incomplete understanding of how computational flexibility is implemented at the level of prefrontal neurons and networks. To better understand the neural mechanisms of computational flexibility, we simultaneously recorded the electrical activity of groups of single neurons within prefrontal and posterior parietal cortex of monkeys performing a task that required executive control of spatial cognitive processing. In this task, monkeys applied different spatial categorization rules to reassign the same set of visual stimuli to alternative categories on a trial-by-trial basis. We found that single neurons were activated to represent spatially defined categories in a manner that was rule dependent, providing a physiological signature of a cognitive process that was implemented under executive control. We found also that neural signals coding rule-dependent categories were distributed between the parietal and prefrontal cortex—however, not equally. Rule-dependent category signals were stronger, more powerfully modulated by the rule, and earlier to emerge in prefrontal cortex relative to parietal cortex. This suggests that prefrontal cortex may initiate the switch in neural representation at a network level that is important for computational flexibility. PMID:22399773

  20. Causal role of the prefrontal cortex in top-down modulation of visual processing and working memory

    PubMed Central

    Zanto, Theodore P.; Rubens, Michael T.; Thangavel, Arul; Gazzaley, Adam

    2011-01-01

    Selective attention filters information to limit what is encoded and maintained in working memory. Although the prefrontal cortex (PFC) is central to both selective attention and working memory, the underlying neural processes that link these cognitive abilities remain elusive. Using functional magnetic resonance imaging to guide repetitive transcranial magnetic stimulation with electroencephalographic recordings in humans, we perturbed PFC function at the inferior frontal junction prior to participants performing a selective-attention, delayed-recognition task. This resulted in diminished top-down modulation of activity in posterior cortex during early encoding stages, which predicted a subsequent decrement in working memory accuracy. Participants with stronger fronto-posterior functional connectivity displayed greater disruptive effects. Data further suggested that broad alpha band (7–14 Hz) phase coherence subserved this long distance top-down modulation. The results establish top-down modulation mediated by the prefrontal cortex as a causal link between early attentional processes and subsequent memory performance. PMID:21441920

  1. Dopaminergic modulation of endocannabinoid-mediated plasticity at GABAergic synapses in the prefrontal cortex

    PubMed Central

    Chiu, Chiayu Q.; Puente, Nagore; Grandes, Pedro; Castillo, Pablo E.

    2010-01-01

    Similar to dopamine (DA), cannabinoids strongly influence prefrontal cortical functions such as working memory, emotional learning, and sensory perception. While endogenous cannabinoid receptors (CB1Rs) are abundantly expressed in the prefrontal cortex (PFC), very little is known about endocannabinoid (eCB) signaling in this brain region. Recent behavioral and electrophysiological evidence has suggested a functional interplay between the dopamine and cannabinoid receptor systems, although the cellular mechanisms underlying this interaction remain to be elucidated. We examined this issue by combining neuroanatomical and electrophysiological techniques in PFC of rats and mice (both genders). Using immuno-electron microscopy, we show that CB1Rs and dopamine type 2 receptors (D2Rs) co-localize at terminals of symmetrical, presumably GABAergic, synapses in the PFC. Indeed, activation of either receptor can suppress GABA release onto layer 5 pyramidal cells. Furthermore, co-activation of both receptors via repetitive afferent stimulation triggers eCB-mediated long term depression of inhibitory transmission (I-LTD). This I-LTD is heterosynaptic in nature, requiring glutamate release to activate group I metabotropic glutamate receptors (mGluRs). D2Rs most likely facilitate eCB signaling at the presynaptic site as disrupting postsynaptic D2R signaling does not diminish I-LTD. Facilitation of eCB-LTD may be one mechanism by which DA modulates neuronal activity in the PFC and regulates PFC-mediated behavior in vivo. PMID:20505090

  2. Muscarinic and Nicotinic Modulation of Thalamo-Prefrontal Cortex Synaptic Pasticity In Vivo

    PubMed Central

    Bueno-Junior, Lezio Soares; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Romcy-Pereira, Rodrigo Neves; Leite, João Pereira

    2012-01-01

    The mediodorsal nucleus of the thalamus (MD) is a rich source of afferents to the medial prefrontal cortex (mPFC). Dysfunctions in the thalamo-prefrontal connections can impair networks implicated in working memory, some of which are affected in Alzheimer disease and schizophrenia. Considering the importance of the cholinergic system to cortical functioning, our study aimed to investigate the effects of global cholinergic activation of the brain on MD-mPFC synaptic plasticity by measuring the dynamics of long-term potentiation (LTP) and depression (LTD) in vivo. Therefore, rats received intraventricular injections either of the muscarinic agonist pilocarpine (PILO; 40 nmol/µL), the nicotinic agonist nicotine (NIC; 320 nmol/µL), or vehicle. The injections were administered prior to either thalamic high-frequency (HFS) or low-frequency stimulation (LFS). Test pulses were applied to MD for 30 min during baseline and 240 min after HFS or LFS, while field postsynaptic potentials were recorded in the mPFC. The transient oscillatory effects of PILO and NIC were monitored through recording of thalamic and cortical local field potentials. Our results show that HFS did not affect mPFC responses in vehicle-injected rats, but induced a delayed-onset LTP with distinct effects when applied following PILO or NIC. Conversely, LFS induced a stable LTD in control subjects, but was unable to induce LTD when applied after PILO or NIC. Taken together, our findings show distinct modulatory effects of each cholinergic brain activation on MD-mPFC plasticity following HFS and LFS. The LTP-inducing action and long-lasting suppression of cortical LTD induced by PILO and NIC might implicate differential modulation of thalamo-prefrontal functions under low and high input drive. PMID:23118873

  3. Perceptual decision-making difficulty modulates feedforward effective connectivity to the dorsolateral prefrontal cortex

    PubMed Central

    Lamichhane, Bidhan; Dhamala, Mukesh

    2015-01-01

    Diverse cortical structures are known to coordinate activity as a network in relaying and processing of visual information to discriminate visual objects. However, how this discrimination is achieved is still largely unknown. To contribute to answering this question, we used face-house categorization tasks with three levels of noise in face and house images in functional magnetic resonance imaging (fMRI) experiments involving thirty-three participants. The behavioral performance error and response time (RT) were correlated with noise in face-house images. We then built dynamical causal models (DCM) of fMRI blood-oxygenation level dependent (BOLD) signals from the face and house category-specific regions in ventral temporal (VT) cortex, the fusiform face area (FFA) and parahippocampal place area (PPA), and the dorsolateral prefrontal cortex (dlPFC). We found a strong feed-forward intrinsic connectivity pattern from FFA and PPA to dlPFC. Importantly, the feed-forward connectivity to dlPFC was significantly modulated by the perception of both faces and houses. The dlPFC-BOLD activity, the connectivity from FFA and PPA to the dlPFC all increased with noise level. These results suggest that the FFA-PPA-dlPFC network plays an important role for relaying and integrating competing sensory information to arrive at perceptual decisions. PMID:26441596

  4. Task Performance Modulates Functional Connectivity Involving the Dorsolateral Prefrontal Cortex in Patients with Schizophrenia.

    PubMed

    Wu, Shihao; Wang, Huiling; Chen, Cheng; Zou, Jilin; Huang, Huan; Li, Peifu; Zhao, Yilin; Xu, Qizhong; Zhang, Liang; Wang, Hesheng; Pandit, Sanjib; Dahal, Subodh; Chen, Jun; Zhou, Yuan; Jiang, Tianzi; Wang, Gaohua

    2017-01-01

    Previous studies have suggested that patients with schizophrenia and healthy controls exhibit differential activation of and connectivity involving the dorsolateral prefrontal cortex (DLPFC) during working memory tasks, though their findings remain inconsistent. The functional integration perspective further suggests that working memory performance also modulates differences in functional interactions of the DLPFC between patients and controls. To explore this possibility, 45 healthy controls and 45 patients with schizophrenia were recruited to perform a 2-back task during functional magnetic resonance imaging (fMRI). Each group was further divided into two subgroups based on task performance to examine the modulatory effect of performance on functional interactions of the DLPFC, as measured via psychophysiological interaction (PPI) analyses. We observed that, in patients with schizophrenia who exhibited impaired working memory capacity and decreased brain activation/deactivation, functional interactions between the right/left DLPFC and angular cortex were decreased relative to those of healthy controls. Furthermore, we observed an interaction effect of working memory performance and diagnosis on functional connectivity between the right/left DLPFC seed region and posterior regions such as the angular cortex, fusiform gyrus, and middle occipital gyrus. This interaction effect was mainly driven by the negative correlation between functional connectivity and performance in healthy controls, and by the positive correlation in patients with schizophrenia. These results demonstrate the effects of inter-individual differences in working memory performance on functional interactions between the DLPFC and posterior regions in patients with schizophrenia as well as healthy controls, which may shed new light on the neural basis of working memory.

  5. Task Performance Modulates Functional Connectivity Involving the Dorsolateral Prefrontal Cortex in Patients with Schizophrenia

    PubMed Central

    Wu, Shihao; Wang, Huiling; Chen, Cheng; Zou, Jilin; Huang, Huan; Li, Peifu; Zhao, Yilin; Xu, Qizhong; Zhang, Liang; Wang, Hesheng; Pandit, Sanjib; Dahal, Subodh; Chen, Jun; Zhou, Yuan; Jiang, Tianzi; Wang, Gaohua

    2017-01-01

    Previous studies have suggested that patients with schizophrenia and healthy controls exhibit differential activation of and connectivity involving the dorsolateral prefrontal cortex (DLPFC) during working memory tasks, though their findings remain inconsistent. The functional integration perspective further suggests that working memory performance also modulates differences in functional interactions of the DLPFC between patients and controls. To explore this possibility, 45 healthy controls and 45 patients with schizophrenia were recruited to perform a 2-back task during functional magnetic resonance imaging (fMRI). Each group was further divided into two subgroups based on task performance to examine the modulatory effect of performance on functional interactions of the DLPFC, as measured via psychophysiological interaction (PPI) analyses. We observed that, in patients with schizophrenia who exhibited impaired working memory capacity and decreased brain activation/deactivation, functional interactions between the right/left DLPFC and angular cortex were decreased relative to those of healthy controls. Furthermore, we observed an interaction effect of working memory performance and diagnosis on functional connectivity between the right/left DLPFC seed region and posterior regions such as the angular cortex, fusiform gyrus, and middle occipital gyrus. This interaction effect was mainly driven by the negative correlation between functional connectivity and performance in healthy controls, and by the positive correlation in patients with schizophrenia. These results demonstrate the effects of inter-individual differences in working memory performance on functional interactions between the DLPFC and posterior regions in patients with schizophrenia as well as healthy controls, which may shed new light on the neural basis of working memory. PMID:28289394

  6. Self-esteem modulates amygdala-ventrolateral prefrontal cortex connectivity in response to mortality threats.

    PubMed

    Yanagisawa, Kuniaki; Abe, Nobuhito; Kashima, Emiko S; Nomura, Michio

    2016-03-01

    Reminders of death often elicit defensive responses in individuals, especially among those with low self-esteem. Although empirical evidence indicates that self-esteem serves as a buffer against mortality threats, the precise neural mechanism underlying this effect remains unknown. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that self-esteem modulates neural responses to death-related stimuli, especially functional connectivity within the limbic-frontal circuitry, thereby affecting subsequent defensive reactions. As predicted, individuals with high self-esteem subjected to a mortality threat exhibited increased amygdala-ventrolateral prefrontal cortex (VLPFC) connectivity during the processing of death-related stimuli compared with individuals who have low self-esteem. Further analysis revealed that stronger functional connectivity between the amygdala and the VLPFC predicted a subsequent decline in responding defensively to those who threaten one's beliefs. These results suggest that the amygdala-VLPFC interaction, which is modulated by self-esteem, can reduce the defensiveness caused by death-related stimuli, thereby providing a neural explanation for why individuals with high self-esteem exhibit less defensive reactions to mortality threats.

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  9. Altered Dopamine Modulation of Inhibition in the Prefrontal Cortex of Cocaine-Sensitized Rats

    PubMed Central

    Kroener, Sven; Lavin, Antonieta

    2010-01-01

    A functionally hypoactive prefrontal cortex (PFC) is thought to contribute to decreased cognitive inhibitory control over drug-seeking behavior in cocaine addicts. Alterations in PFC dopamine (DA) and γ-aminobutyric acid (GABA) transmission are involved in the development of behavioral sensitization to cocaine, and repeated exposure to cocaine decreases DA D2 receptor (D2R) function in the PFC. We used recordings in PFC slices from adult rats to investigate how repeated cocaine treatment followed by 2 weeks of withdrawal affects DA modulation of GABA transmission and interneuron firing. In agreement with previous results in drug-naïve animals we found that in saline-treated control animals DA (20 μM) modulated evoked inhibitory post-synaptic currents (eIPSCs) in a biphasic, time- and receptor-dependent manner. Activation of D2Rs transiently reduced, whereas D1 receptor activation persistently increased the amplitude of eIPSCs. In cocaine-sensitized animals the D2R-dependent modulation of eIPSCs was abolished and the time course of DA effects was altered. In both saline- and cocaine-treated animals the effects of DA on eIPSCs were paralleled by distinct changes in spontaneous IPSCs (sIPSCs). In cocaine-treated animals the alterations in DA modulation of eIPSCs and sIPSCs correlated with a lack of D2R-specific reduction in action potential-independent GABA release, which might normally oppose D1-dependent increases in GABA transmission. Recordings from interneurons furthermore show that D2R activation can increase current-evoked spike firing in saline, but not in cocaine-treated animals. Altered DA regulation of inhibition during cocaine withdrawal could disturb normal cortical processing and contribute to a hypoactive PFC. PMID:20664581

  10. Altered dopamine modulation of inhibition in the prefrontal cortex of cocaine-sensitized rats.

    PubMed

    Kroener, Sven; Lavin, Antonieta

    2010-10-01

    A functionally hypoactive prefrontal cortex (PFC) is thought to contribute to decreased cognitive inhibitory control over drug-seeking behavior in cocaine addicts. Alterations in PFC dopamine (DA) and γ-aminobutyric acid (GABA) transmission are involved in the development of behavioral sensitization to cocaine, and repeated exposure to cocaine decreases DA D2 receptor (D2R) function in the PFC. We used recordings in PFC slices from adult rats to investigate how repeated cocaine treatment followed by 2 weeks of withdrawal affects DA modulation of GABA transmission and interneuron firing. In agreement with previous results in drug-naïve animals we found that in saline-treated control animals DA (20 μM) modulated evoked inhibitory post-synaptic currents (eIPSCs) in a biphasic, time- and receptor-dependent manner. Activation of D2Rs transiently reduced, whereas D1 receptor activation persistently increased the amplitude of eIPSCs. In cocaine-sensitized animals the D2R-dependent modulation of eIPSCs was abolished and the time course of DA effects was altered. In both saline- and cocaine-treated animals the effects of DA on eIPSCs were paralleled by distinct changes in spontaneous IPSCs (sIPSCs). In cocaine-treated animals the alterations in DA modulation of eIPSCs and sIPSCs correlated with a lack of D2R-specific reduction in action potential-independent GABA release, which might normally oppose D1-dependent increases in GABA transmission. Recordings from interneurons furthermore show that D2R activation can increase current-evoked spike firing in saline, but not in cocaine-treated animals. Altered DA regulation of inhibition during cocaine withdrawal could disturb normal cortical processing and contribute to a hypoactive PFC.

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

    PubMed Central

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

    2013-01-01

    A common source of variance (i.e., “general intelligence”) underlies an individual's performance across diverse tests of cognitive ability, and evidence indicates that the processing efficacy of working memory may serve as one such source of common variance. One component of working memory, selective attention, has been reported to co-vary with general intelligence, and dopamine D1 signaling in prefrontal cortex can modulate attentional abilities. Based on their aggregate performance across five diverse tests of learning, here we characterized the general cognitive ability (GCA) of CD-1 outbred mice. In response to a D1 agonist (SKF82958, 1 mg/kg), we then assessed the relationship between GCA and activation of D1 receptor (D1R)-containing neurons in the prelimbic region of the medial prefrontal cortex, the agranular insular cortex, and the dorsomedial striatum. Increased activation of D1R-containing neurons in the prelimbic cortex (but not the agranular insular cortex or dorsomedial striatum) was observed in animals of high GCA relative to those of low GCA (quantified by c-Fos activation in response to the D1 agonist). However, a Western blot analysis revealed no differences in the density of D1Rs in the prelimbic cortex between animals of high and low GCA. Last, it was observed that working memory training promoted an increase in animals’ GCA and enhanced D1R-mediated neuronal activation in the prelimbic cortex. These results suggest that the sensitivity (but not density) of D1Rs in the prelimbic cortex may both regulate GCA and be a target for working memory training. PMID:24129098

  12. The principal features and mechanisms of dopamine modulation in the prefrontal cortex.

    PubMed

    Seamans, Jeremy K; Yang, Charles R

    2004-09-01

    Mesocortical [corrected] dopamine (DA) inputs to the prefrontal cortex (PFC) play a critical role in normal cognitive process and neuropsychiatic pathologies. This DA input regulates aspects of working memory function, planning and attention, and its dysfunctions may underlie positive and negative symptoms and cognitive deficits associated with schizophrenia. Despite intense research, there is still a lack of clear understanding of the basic principles of actions of DA in the PFC. In recent years, there has been considerable efforts by many groups to understand the cellular mechanisms of DA modulation of PFC neurons. However, the results of these efforts often lead to contradictions and controversies. One principal feature of DA that is agreed by most researchers is that DA is a neuromodulator and is clearly not an excitatory or inhibitory neurotransmitter. The present article aims to identify certain principles of DA mechanisms by drawing on published, as well as unpublished data from PFC and other CNS sites to shed light on aspects of DA neuromodulation and address some of the existing controversies. Eighteen key features about DA modulation have been identified. These points directly impact on the end result of DA neuromodulation, and in some cases explain why DA does not yield identical effects under all experimental conditions. It will become apparent that DA's actions in PFC are subtle and depend on a variety of factors that can no longer be ignored. Some of these key factors include distinct bell-shaped dose-response profiles of postsynaptic DA effects, different postsynaptic responses that are contingent on the duration of DA receptor stimulation, prolonged duration effects, bidirectional effects following activation of D1 and D2 classes of receptors and membrane potential state and history dependence of subsequent DA actions. It is hoped that these factors will be borne in mind in future research and as a result a more consistent picture of DA

  13. MRI volumetry of prefrontal cortex

    NASA Astrophysics Data System (ADS)

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

    1995-05-01

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

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

    PubMed

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

    2015-09-01

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

  15. Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

    PubMed

    Pripfl, Jürgen; Lamm, Claus

    2015-02-01

    Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits.

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

    PubMed

    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.

  17. Molecular Modulation of Prefrontal Cortex: Rational Development of Treatments for Psychiatric Disorders

    PubMed Central

    Gamo, Nao J.; Arnsten, Amy F.T.

    2011-01-01

    Dysfunction of the prefrontal cortex (PFC) is a central feature of many psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia and bipolar disorder. Thus, understanding molecular influences on PFC function through basic research in animals is essential to rational drug development. In this review, we discuss the molecular signaling events initiated by norepinephrine and dopamine that strengthen working memory function mediated by the dorsolateral PFC under optimal conditions, and weaken working memory function during uncontrollable stress. We also discuss how these intracellular mechanisms can be compromised in psychiatric disorders, and how novel treatments based on these findings may restore a molecular environment conducive to PFC regulation of behavior, thought and emotion. Examples of successful translation from animals to humans include guanfacine for the treatment of ADHD and related PFC disorders, and prazosin for the treatment of PTSD. PMID:21480691

  18. Molecular modulation of prefrontal cortex: rational development of treatments for psychiatric disorders.

    PubMed

    Gamo, Nao J; Arnsten, Amy F T

    2011-06-01

    Dysfunction of the prefrontal cortex (PFC) is a central feature of many psychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), schizophrenia, and bipolar disorder. Thus, understanding molecular influences on PFC function through basic research in animals is essential to rational drug development. In this review, we discuss the molecular signaling events initiated by norepinephrine and dopamine that strengthen working memory function mediated by the dorsolateral PFC under optimal conditions, and weaken working memory function during uncontrollable stress. We also discuss how these intracellular mechanisms can be compromised in psychiatric disorders, and how novel treatments based on these findings may restore a molecular environment conducive to PFC regulation of behavior, thought and emotion. Examples of successful translation from animals to humans include guanfacine for the treatment of ADHD and related PFC disorders, and prazosin for the treatment of PTSD.

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

    SciTech Connect

    Hegarty, A.A.; Vogel, W.H. )

    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.

  20. Disruption of Akt signaling decreases dopamine sensitivity in modulation of inhibitory synaptic transmission in rat prefrontal cortex.

    PubMed

    Li, Yan-Chun; Yang, Sha-Sha; Gao, Wen-Jun

    2016-09-01

    Akt is a serine/threonine kinase, which is dramatically reduced in the prefrontal cortex (PFC) of patients with schizophrenia, and a deficiency in Akt1 results in PFC function abnormalities. Although the importance of Akt in dopamine (DA) transmission is well established, how impaired Akt signaling affects the DA modulation of synaptic transmission in the PFC has not been characterized. Here we show that Akt inhibitors significantly decreased receptor sensitivity to DA by shifting DA modulation of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in prefrontal cortical neurons. Akt inhibition caused a significant decrease in synaptic dopamine D2 receptor (D2R) levels with high-dose DA exposure. In addition, Akt inhibition failed to affect DA modulation of IPSCs after blockade of β-arrestin 2. β-arrestin 2-mediated interaction of clathrin with D2R was enhanced by co-application of a Akt inhibitor and DA. Taken together, the reduced response in DA modulation of inhibitory transmission mainly involved β-arrestin 2-dependent D2R desensitization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Modulators in concert for cognition: modulator interactions in the prefrontal cortex

    PubMed Central

    Briand, Lisa A.; Gritton, Howard; Howe, William M.; Young, Damon A.; Sarter, Martin

    2007-01-01

    Research on the regulation and function of ascending noradrenergic, dopaminergic, serotonergic, and cholinergic systems has focused on the organization and function of individual systems. In contrast, evidence describing co-activation and interactions between multiple neuromodulatory systems has remained scarce. However, commonalities in the anatomical organization of these systems and overlapping evidence concerning the post-synaptic effects of neuromodulators strongly suggest that these systems are recruited in concert; they influence each other and simultaneously modulate their target circuits. Therefore, evidence on the regulatory and functional interactions between these systems is considered essential for revealing the role of neuromodulators. This postulate extends to contemporary neurobiological hypotheses of major neuropsychiatric disorders. These hypotheses have focused largely on aberrations in the integrity or regulation of individual ascending modulatory systems, with little regard for the likely possibility that dysregulation in multiple ascending neuromodulatory systems and their interactions contribute essentially to the symptoms of these disorders. This review will paradigmatically focus on neuromodulator interactions in the PFC and be further constrained by an additional focus on their role in cognitive functions. Recent evidence indicates that individual neuromodulators, in addition to their general state-setting or gating functions, encode specific cognitive operations, further substantiating the importance of research concerning the parallel recruitment of neuromodulator systems and interactions between these systems. PMID:17681661

  2. Neuropeptide Y Impairs Retrieval of Extinguished Fear and Modulates Excitability of Neurons in the Infralimbic Prefrontal Cortex.

    PubMed

    Vollmer, Lauren L; Schmeltzer, Sarah; Schurdak, Jennifer; Ahlbrand, Rebecca; Rush, Jennifer; Dolgas, Charles M; Baccei, Mark L; Sah, Renu

    2016-01-27

    Neuropeptide Y (NPY), a 36 aa peptide, regulates stress and emotional behaviors. Preclinical and clinical studies support an association of NPY with trauma-evoked syndromes such as posttraumatic stress disorder (PTSD), although the exact contribution of NPY is not clear. In the current study, we examined functional attributes of NPY in the infralimbic (IL) cortex, an area that regulates fear memories and is reported to be hypoactive in PTSD. Carriers of NPY gene polymorphism rs16147 have been reported to have elevated prefrontal NPY expression. Infusion of NPY into the IL cortex in rats significantly impaired fear extinction memory without affecting conditioned fear expression or acquisition of extinction. Neuroendocrine stress response, depression-like behavior, and working memory performance were not affected by NPY infusion into the IL. The NPY Y1 receptor antagonist BIBO3304 completely abolished NPY effects on fear extinction retrieval. Y1 receptor expression was localized on CaMKII-positive pyramidal projection neurons and GAD67-positive interneurons in the IL. Patch-clamp recordings revealed increased inhibitory synaptic transmission onto IL projection neurons in the presence of NPY. Thus, NPY dampens excitability of IL projection neurons and impairs retrieval of extinction memory by inhibiting consolidation of extinction. Of relevance to PTSD, elevation of prefrontal NPY attributable to the genetic polymorphism rs16147 may contribute to IL hypoactivity, resulting in impaired extinction memory and susceptibility to the disorder. Neuropeptide Y (NPY), a stress modulatory transmitter, is associated with posttraumatic stress disorder (PTSD). Contribution of NPY to PTSD symptomology is unclear. PTSD patients have reduced activity in the infralimbic (IL) subdivision of the medial prefrontal cortex (mPFC), associated with compromised extinction memory. No information exists on fear modulation by NPY in the IL cortex, although NPY and NPY receptors are abundant in

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

    PubMed

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

    2015-12-01

    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. 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. 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. 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.

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

    NASA Astrophysics Data System (ADS)

    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. Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

    PubMed Central

    Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

    2017-01-01

    The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

  6. Cell-type-specific modulation of targets and distractors by dopamine D1 receptors in primate prefrontal cortex

    PubMed Central

    Jacob, Simon N.; Stalter, Maximilian; Nieder, Andreas

    2016-01-01

    The prefrontal cortex (PFC) is crucial for maintaining relevant information in working memory and resisting interference. PFC neurons are strongly regulated by dopamine, but it is unknown whether dopamine receptors are involved in protecting target memories from distracting stimuli. We investigated the prefrontal circuit dynamics and dopaminergic modulation of targets and distractors in monkeys trained to ignore interfering stimuli in a delayed-match-to-numerosity task. We found that dopamine D1 receptors (D1Rs) modulate the recovery of task-relevant information following a distracting stimulus. The direction of modulation is cell-type-specific: in putative pyramidal neurons, D1R inhibition enhances and D1R stimulation attenuates coding of the target stimulus after the interference, while the opposite pattern is observed in putative interneurons. Our results suggest that dopaminergic neuromodulation of PFC circuits regulates mental representations of behaviourally relevant stimuli that compete with task-irrelevant input and could play a central role for cognitive functioning in health and disease. PMID:27807366

  7. Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex.

    PubMed

    Klavir, Oded; Prigge, Matthias; Sarel, Ayelet; Paz, Rony; Yizhar, Ofer

    2017-06-01

    Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA-mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA-mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.

  8. Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats

    PubMed Central

    Andino-Pavlovsky, Victoria; Souza, Annie C.; Scheffer-Teixeira, Robson; Tort, Adriano B. L.; Etchenique, Roberto; Ribeiro, Sidarta

    2017-01-01

    Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC. PMID:28536507

  9. Atypical modulation of medial prefrontal cortex to self-referential comments in generalized social phobia.

    PubMed

    Blair, Karina S; Geraci, Marilla; Otero, Marcela; Majestic, Catherine; Odenheimer, Stephanie; Jacobs, Madeline; Blair, R J R; Pine, Daniel S

    2011-07-30

    Generalized social phobia (GSP) involves the fear of being negatively evaluated. Previous work suggests that self-referentiality, mediated by the medial prefrontal cortex (MFPC), plays an important role in the disorder. However, it is not clear whether this anomalous MPFC response to self-related information in patients with GSP concerns an increased representation of their own or others' opinions. In this article, we examine whether GSP is associated with increased response to own (1st person) or other individuals' (2nd person) opinions relative to healthy individuals. Unmedicated individuals with GSP (n=15) and age-, IQ-, and gender-matched comparison individuals (n=15) read 1st (e.g., I'm ugly), and 2nd (e.g., You're ugly) person viewpoint comments during functional magnetic resonance imaging. We observed significant group-by-viewpoint interactions within the ventral MPFC. Whereas the healthy comparison individuals showed significantly increased (or less decreased) BOLD responses to 1st relative to 2nd person viewpoints, the patients showed significantly increased responses to 2nd relative to 1st person viewpoints. The reduced BOLD responses to 1st person viewpoint comments shown by the patients correlated significantly with severity of social anxiety symptom severity. These results underscore the importance of dysfunctional self-referential processing and MPFC in GSP. We believe that these data reflect a reorganization of self-referential reasoning in the disorder with a self-concept perhaps atypically related to the view of others.

  10. Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats.

    PubMed

    Andino-Pavlovsky, Victoria; Souza, Annie C; Scheffer-Teixeira, Robson; Tort, Adriano B L; Etchenique, Roberto; Ribeiro, Sidarta

    2017-01-01

    Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC.

  11. Medial prefrontal cortex stimulation modulates irony processing as indexed by the N400.

    PubMed

    Baptista, Nathalia Ishikawa; Manfredi, Mirella; Boggio, Paulo Sérgio

    2017-07-20

    In this study, we investigated whether the ERP responses observed during a verbal irony comprehension task might represent the cortical manifestation of the Medial Prefrontal Cortex (MPFC) activity. We performed a tDCS-EEG study in which we analyzed the effects of tDCS polarities (anode, cathode, sham) over the MPFC during a verbal irony task. We presented visual short stories portraying everyday situations followed by written statements in either an ironic or literal condition, whose meaning was referred to in the previous context. We manipulated the valence of the stimuli by presenting positive sentences or negative sentences in the ironic and literal conditions. The results revealed that the participants who received the anodal stimulation showed no differences in the N400 amplitude in response to the literal and the ironic condition. This could suggest that anodal stimulation has modulatory effects on N400 responses during irony comprehension. Our results indicated that the MPFC might be critical in accessing ironic information at the initial stage of irony comprehension. Finally, we found that the ironic compliments were more difficult to understand compared to the literal ones, suggesting that irony comprehension is affected by the valence of the information presented.

  12. Cholinergic modulation of the medial prefrontal cortex: the role of nicotinic receptors in attention and regulation of neuronal activity

    PubMed Central

    Bloem, Bernard; Poorthuis, Rogier B.; Mansvelder, Huibert D.

    2014-01-01

    Acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) is crucial for normal cognitive performance. Despite the fact that many have studied how ACh affects neuronal processing in the mPFC and thereby influences attention behavior, there is still a lot unknown about how this occurs. Here we will review the evidence that cholinergic modulation of the mPFC plays a role in attention and we will summarize the current knowledge about the role between ACh receptors (AChRs) and behavior and how ACh receptor activation changes processing in the cortical microcircuitry. Recent evidence implicates fast phasic release of ACh in cue detection and attention. This review will focus mainly on the fast ionotropic nicotinic receptors and less on the metabotropic muscarinic receptors. Finally, we will review limitations of the existing studies and address how innovative technologies might push the field forward in order to gain understanding into the relation between ACh, neuronal activity and behavior. PMID:24653678

  13. Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin

    PubMed Central

    Liu, Wenhua; Yuen, Eunice Y.; Allen, Patrick B.; Feng, Jian; Greengard, Paul; Yan, Zhen

    2006-01-01

    The noradrenergic system in the prefrontal cortex (PFC) is involved in many physiological and psychological processes, including working memory and mood control. To understand the functions of the noradrenergic system, we examined the regulation of NMDA receptors (NMDARs), key players in cognition and emotion, by α1- and α2-adrenergic receptors (α1-ARs, α2-ARs) in PFC pyramidal neurons. Applying norepinephrine or a norepinephrine transporter inhibitor reduced the amplitude but not paired-pulse ratio of NMDAR-mediated excitatory postsynaptic currents (EPSC) in PFC slices. Specific α1-AR or α2-AR agonists also decreased NMDAR-EPSC amplitude and whole-cell NMDAR current amplitude in dissociated PFC neurons. The α1-AR effect depended on the phospholipase C–inositol 1,4,5-trisphosphate–Ca2+ pathway, whereas the α2-AR effect depended on protein kinase A and the microtubule-based transport of NMDARs that is regulated by ERK signaling. Furthermore, two members of the RGS family, RGS2 and RGS4, were found to down-regulate the effect of α1-AR on NMDAR currents, whereas only RGS4 was involved in inhibiting α2-AR regulation of NMDAR currents. The regulating effects of RGS2/4 on α1-AR signaling were lost in mutant mice lacking spinophilin, which binds several RGS members and G protein-coupled receptors, whereas the effect of RGS4 on α2-AR signaling was not altered in spinophilin-knockout mice. Our work suggests that activation of α1-ARs or α2-ARs suppresses NMDAR currents in PFC neurons by distinct mechanisms. The effect of α1-ARs is modified by RGS2/4 that are recruited to the receptor complex by spinophilin, whereas the effect of α2-ARs is modified by RGS4 independent of spinophilin. PMID:17101972

  14. Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex

    PubMed Central

    Cathel, Alessandra M.; Reyes, Beverly A. S.; Wang, Qin; Palma, Jonathan; Mackie, Kenneth; Bockstaele, Elisabeth J. Van; Kirby, Lynn G.

    2014-01-01

    Endocannabinoids acting at the cannabinoid type 1 receptor (CB1R) are known to regulate attention, cognition and mood. Previous studies have shown that, in the rat medial prefrontal cortex (mPFC), CB1R agonists increase norepinephrine release, an effect that may be attributed, in part, to CB1Rs localized to noradrenergic axon terminals. The present study was aimed at further characterizing functional interactions between CB1R and adrenergic receptor (AR) systems in the mPFC using in-vitro intracellular electrophysiology and high-resolution neuroanatomical techniques. Whole-cell patch-clamp recordings of layer V/VI cortical pyramidal neurons in rats revealed that both acute and chronic treatment with the synthetic CB1R agonist WIN 55,212-2 blocked elevations in cortical pyramidal cell excitability and increases in input resistance evoked by the α2-adrenergic receptor (α2-AR) agonist clonidine, suggesting a desensitization of α2-ARs. These CB1R–α2-AR interactions were further shown to be both action potential- and gamma-aminobutyric acid-independent. To better define sites of cannabinoid–AR interactions, we localized α2A-ARs in a genetically modified mouse that expressed a hemoagglutinin (HA) tag downstream of the α2A-AR promoter. Light and electron microscopy indicated that HA-α2A-AR was distributed in axon terminals and somatodendritic processes especially in layer V of the mPFC. Triple-labeling immunocytochemistry revealed that α2A-AR and CB1R were localized to processes that contained dopamine-β-hydroxylase, a marker of norepinephrine. Furthermore, HA-α2A-AR was localized to processes that were directly apposed to CB1R. These findings suggest multiple sites of interaction between cortical cannabinoid–adrenergic systems that may contribute to understanding the effect of cannabinoids on executive functions and mood. PMID:25131562

  15. Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

    PubMed Central

    Chun, Lauren E.; Hinds, Laura R.; Spencer, Robert L.

    2016-01-01

    Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation. PMID:26901093

  16. ALCOHOL AND THE PREFRONTAL CORTEX

    PubMed Central

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

    2013-01-01

    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. PMID:20813246

  17. Task-relevancy effects on movement-related gating are modulated by continuous theta-burst stimulation of the dorsolateral prefrontal cortex and primary somatosensory cortex.

    PubMed

    Brown, Katlyn E; Ferris, Jennifer K; Amanian, Mohammad A; Staines, W Richard; Boyd, Lara A

    2015-03-01

    Movement-related gating ensures that decreased somatosensory information from external stimulation reaches the cortex during movement when compared to resting levels; however, gating may be influenced by task-relevant manipulations, such that increased sensory information ascends to the cortex when information is relevant to goal-based actions. These task-relevancy effects are hypothesized to be controlled by a network involving the dorsolateral prefrontal cortex (DLPFC) based on this region's known role in selective attention, modulating the primary somatosensory cortex (S1). The purpose of the current study was first to verify task-relevancy influences on movement-related gating in the upper limb, and second to test the contribution of the DLPFC and the primary somatosensory cortex (S1) to these relevancy effects. Ten healthy participants received median nerve stimulation at the left wrist during three conditions: rest, task-irrelevant movement, and task-relevant movement. Cortical responses to median nerve stimulations were measured in the form of somatosensory evoked potentials (SEPs). The three conditions were collected on a baseline day and on two separate days following continuous theta-burst (cTBS), which transiently reduces cortical excitability, over either the contralateral S1 or DLPFC. Results demonstrated a significant interaction between stimulation and condition, with a priori contrasts revealing that cTBS over either S1 or DLPFC diminished the relevancy-based modulation of SEP amplitudes; however, the degree of this effect was different. These results indicate that DLPFC influences over S1 are involved in the facilitation of relevant sensory information during movement.

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

    PubMed

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

    2017-03-02

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT2AR activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT2AR blockade does not seem to affect the amygdala-striatal projection.

  19. Target-specific modulation of the descending prefrontal cortex inputs to the dorsal raphe nucleus by cannabinoids

    PubMed Central

    Geddes, Sean D.; Assadzada, Saleha; Lemelin, David; Sokolovski, Alexandra; Bergeron, Richard; Haj-Dahmane, Samir; Béïque, Jean-Claude

    2016-01-01

    Serotonin (5-HT) neurons located in the raphe nuclei modulate a wide range of behaviors by means of an expansive innervation pattern. In turn, the raphe receives a vast array of synaptic inputs, and a remaining challenge lies in understanding how these individual inputs are organized, processed, and modulated in this nucleus to contribute ultimately to the core coding features of 5-HT neurons. The details of the long-range, top-down control exerted by the medial prefrontal cortex (mPFC) in the dorsal raphe nucleus (DRN) are of particular interest, in part, because of its purported role in stress processing and mood regulation. Here, we found that the mPFC provides a direct monosynaptic, glutamatergic drive to both DRN 5-HT and GABA neurons and that this architecture was conducive to a robust feed-forward inhibition. Remarkably, activation of cannabinoid (CB) receptors differentially modulated the mPFC inputs onto these cell types in the DRN, in effect regulating the synaptic excitatory/inhibitory balance governing the excitability of 5-HT neurons. Thus, the CB system dynamically reconfigures the processing features of the DRN, a mood-related circuit believed to provide a concerted and distributed regulation of the excitability of large ensembles of brain networks. PMID:27114535

  20. Transcranial direct current stimulation of the prefrontal cortex modulates working memory performance: combined behavioural and electrophysiological evidence

    PubMed Central

    2011-01-01

    Background Transcranial direct current stimulation (tDCS) is a technique that can systematically modify behaviour by inducing changes in the underlying brain function. In order to better understand the neuromodulatory effect of tDCS, the present study examined the impact of tDCS on performance in a working memory (WM) task and its underlying neural activity. In two experimental sessions, participants performed a letter two-back WM task after sham and either anodal or cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). Results Results showed that tDCS modulated WM performance by altering the underlying oscillatory brain activity in a polarity-specific way. We observed an increase in WM performance and amplified oscillatory power in the theta and alpha bands after anodal tDCS whereas cathodal tDCS interfered with WM performance and decreased oscillatory power in the theta and alpha bands under posterior electrode sides. Conclusions The present study demonstrates that tDCS can alter WM performance by modulating the underlying neural oscillations. This result can be considered an important step towards a better understanding of the mechanisms involved in tDCS-induced modulations of WM performance, which is of particular importance, given the proposal to use electrical brain stimulation for the therapeutic treatment of memory deficits in clinical settings. PMID:21211016

  1. TOP-DOWN CONTROL OF MOTOR CORTEX ENSEMBLES BY DORSOMEDIAL PREFRONTAL CORTEX

    PubMed Central

    Narayanan, Nandakumar S.; Laubach, Mark

    2007-01-01

    SUMMARY 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 predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding. PMID:17145511

  2. Modulation of Cross-Frequency Coupling by Novel and Repeated Stimuli in the Primate Ventrolateral Prefrontal Cortex

    PubMed Central

    Tsunada, Joji; Baker, Allison E.; Christison-Lagay, Kate L.; Davis, Selina J.; Cohen, Yale E.

    2011-01-01

    Adaptive behavior depends on an animal’s ability to ignore uninformative stimuli, such as repeated presentations of the same stimulus, and, instead, detect informative, novel stimuli in its environment. The primate prefrontal cortex (PFC) is known to play a central role in this ability. However, the neural mechanisms underlying the ability to differentiate between repeated and novel stimuli are not clear. We hypothesized that the coupling between different frequency bands of the local field potential (LFP) underlies the PFC’s role in differentiating between repeated and novel stimuli. Specifically, we hypothesized that whereas the presentation of a novel-stimulus induces strong cross-frequency coupling, repeated presentations of the same stimulus attenuates this coupling. To test this hypothesis, we recorded LFPs from the ventrolateral PFC (vPFC) of rhesus monkeys while they listened to a novel vocalization and repeated presentations of the same vocalization. We found that the cross-frequency coupling between the gamma-band amplitude and theta-band phase of the LFP was modulated by repeated presentations of a stimulus. During the first (novel) presentation of a stimulus, gamma-band activity was modulated by the theta-band phase. However, with repeated presentations of the same stimulus, this cross-frequency coupling was attenuated. These results suggest that cross-frequency coupling may play a role in the neural computations that underlie the differentiation between novel and repeated stimuli in the vPFC. PMID:21941517

  3. Not so bad: avoidance and aversive discounting modulate threat appraisal in anterior cingulate and medial prefrontal cortex

    PubMed Central

    Schlund, Michael W.; Brewer, Adam T.; Richman, David M.; Magee, Sandy K.; Dymond, Simon

    2015-01-01

    The dorsal anterior cingulate (adACC) and dorsal medial prefrontal cortex (dmPFC) play a central role in the discrimination and appraisal of threatening stimuli. Yet, little is known about what specific features of threatening situations recruit these regions and how avoidance may modulate appraisal and activation through prevention of aversive events. In this investigation, 30 healthy adults underwent functional neuroimaging while completing an avoidance task in which responses to an Avoidable CS+ threat prevented delivery of an aversive stimulus, but not to an Unavoidable CS+ threat. Extinction testing was also completed where CSs were presented without aversive stimulus delivery and an opportunity to avoid. The Avoidable CS+ relative to the Unavoidable CS+ was associated with reductions in ratings of negative valence, fear, and US expectancy and activation. Greater regional activation was consistently observed to the Unavoidable CS+ during avoidance, which declined during extinction. Individuals exhibiting greater aversive discounting—that is, those more avoidant of immediate monetary loss compared to a larger delayed loss—also displayed greater activation to the Unavoidable CS+, highlighting aversive discounting as a significant individual difference variable. These are the first results linking adACC/dmPFC reactivity to avoidance-based reductions of aversive events and modulation of activation by individual differences in aversive discounting. PMID:26113813

  4. Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex.

    PubMed

    Felix-Ortiz, A C; Burgos-Robles, A; Bhagat, N D; Leppla, C A; Tye, K M

    2016-05-03

    The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) modulate anxiety and social behaviors. It remains to be elucidated, however, whether direct projections from the BLA to the mPFC play a functional role in these behaviors. We used optogenetic approaches in behaving mice to either activate or inhibit BLA inputs to the mPFC during behavioral assays that assess anxiety-like behavior and social interaction. Channelrhodopsin-2 (ChR2)-mediated activation of BLA inputs to the mPFC produced anxiogenic effects in the elevated plus maze and open field test, whereas halorhodopsin (NpHR)-mediated inhibition produced anxiolytic effects. Furthermore, activation of the BLA-mPFC pathway reduced social interaction in the resident-intruder test, whereas inhibition facilitated social interaction. These results establish a causal relationship between activity in the BLA-mPFC pathway and the bidirectional modulation of anxiety-related and social behaviors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Direct current induced short-term modulation of the left dorsolateral prefrontal cortex while learning auditory presented nouns

    PubMed Central

    Elmer, Stefan; Burkard, Marcel; Renz, Basil; Meyer, Martin; Jancke, Lutz

    2009-01-01

    Background Little is known about the contribution of transcranial direct current stimulation (tDCS) to the exploration of memory functions. The aim of the present study was to examine the behavioural effects of right or left-hemisphere frontal direct current delivery while committing to memory auditory presented nouns on short-term learning and subsequent long-term retrieval. Methods Twenty subjects, divided into two groups, performed an episodic verbal memory task during anodal, cathodal and sham current application on the right or left dorsolateral prefrontal cortex (DLPFC). Results Our results imply that only cathodal tDCS elicits behavioural effects on verbal memory performance. In particular, left-sided application of cathodal tDCS impaired short-term verbal learning when compared to the baseline. We did not observe tDCS effects on long-term retrieval. Conclusion Our results imply that the left DLPFC is a crucial area involved in short-term verbal learning mechanisms. However, we found further support that direct current delivery with an intensity of 1.5 mA to the DLPFC during short-term learning does not disrupt longer lasting consolidation processes that are mainly known to be related to mesial temporal lobe areas. In the present study, we have shown that the tDCS technique has the potential to modulate short-term verbal learning mechanism. PMID:19604352

  6. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex modulates early affective processing.

    PubMed

    Zwanzger, Peter; Steinberg, Christian; Rehbein, Maimu Alissa; Bröckelmann, Ann-Kathrin; Dobel, Christian; Zavorotnyy, Maxim; Domschke, Katharina; Junghöfer, Markus

    2014-11-01

    The dorsolateral prefrontal cortex (dlPFC) has often been suggested as a key modulator of emotional stimulus appraisal and regulation. Therefore, in clinical trials, it is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). In spite of various encouraging reports that demonstrate beneficial effects of rTMS in anxiety disorders, psychophysiological studies exploring the underlying neural mechanisms are sparse. Here we investigated how inhibitory rTMS influences early affective processing when applied over the right dlPFC. Before and after rTMS or sham stimulation, subjects viewed faces with fearful or neutral expressions while whole-head magnetoencephalography (MEG) was recorded. Due to the disrupted functioning of the right dlPFC, visual processing in bilateral parietal, temporal, and occipital areas was amplified starting at around 90 ms after stimulus onset. Moreover, increased fear-specific activation was found in the right TPJ area in a time-interval between 110 and 170 ms. These neurophysiological effects were reflected in slowed reaction times for fearful, but not for neutral faces in a facial expression identification task while there was no such effect on a gender discrimination control task. Our study confirms the specific and important role of the dlPFC in regulation of early emotional attention and encourages future clinical research to use minimal invasive methods such as transcranial magnetic (TMS) or direct current stimulation (tDCS).

  7. Mapping Prefrontal Cortex Functions in Human Infancy

    ERIC Educational Resources Information Center

    Grossmann, Tobias

    2013-01-01

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

  8. Mapping Prefrontal Cortex Functions in Human Infancy

    ERIC Educational Resources Information Center

    Grossmann, Tobias

    2013-01-01

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

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

    PubMed Central

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

    2010-01-01

    In a complex world, a sensory cue may prompt different actions in different contexts. A laboratory example of context-dependent sensory processing is the two-stimulus-interval discrimination task. In each trial, a first stimulus (f1) must be stored in short-term memory and later compared with a second stimulus (f2), for the animal to come to a binary decision. Prefrontal cortex (PFC) neurons need to interpret the f1 information in one way (perhaps with a positive weight) and the f2 information in an opposite way (perhaps with a negative weight), although they come from the very same secondary somatosensory cortex (S2) neurons; therefore, a functional sign inversion is required. This task thus provides a clear example of context-dependent processing. Here we develop a biologically plausible model of a context-dependent signal transformation of the stimulus encoding from S2 to PFC. To ground our model in experimental neurophysiology, we use neurophysiological data recorded by R. Romo’s laboratory from both cortical area S2 and PFC in monkeys performing the task. Our main goal is to use experimentally observed context-dependent modulations of firing rates in cortical area S2 as the basis for a model that achieves a context-dependent inversion of the sign of S2 to PFC connections. This is done without requiring any changes in connectivity (Salinas, 2004b). We (1) characterize the experimentally observed context-dependent firing rate modulation in area S2, (2) construct a model that results in the sign transformation, and (3) characterize the robustness and consequent biological plausibility of the model. PMID:19494146

  10. Prefrontal cortex glutamate and extraversion

    PubMed Central

    Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-01-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states. PMID:22016442

  11. Prefrontal cortex glutamate and extraversion.

    PubMed

    Grimm, Simone; Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-10-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states.

  12. Perceived Chronic Stress Exposure Modulates Reward-Related Medial Prefrontal Cortex Responses to Acute Stress in Depression

    PubMed Central

    Kumar, Poornima; Slavich, George M.; Berghorst, Lisa H.; Treadway, Michael T.; Brooks, Nancy H.; Dutra, Sunny J.; Greve, Douglas N.; O'Donovan, Aoife; Bleil, Maria E.; Maninger, Nicole; Pizzagalli, Diego A.

    2015-01-01

    Introduction Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. Methods In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI. Results Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r = 0.79, p = 0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r = 0.79) and no-stress (r = −0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC grey matter, but functional findings remained when accounting for structural differences. Limitation Small sample size, which warrants replication. Conclusion Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression. PMID:25898329

  13. Structural Integrity of the Prefrontal Cortex Modulates Electrocortical Sensitivity to Reward

    PubMed Central

    Parvaz, Muhammad A.; Konova, Anna B.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2015-01-01

    The P300 is a known ERP component assessing stimulus value, including the value of a monetary reward. In parallel, the incentive value of reinforcers relies on the PFC, a major cortical projection region of the mesocortical reward pathway. Here we show a significant positive correlation between P300 response to money (vs. no money) with PFC gray matter volume in the OFC, ACC, and dorsolateral and ventrolateral PFC in healthy control participants. In contrast, individuals with cocaine use disorders showed compromises in both P300 sensitivity to money and PFC gray matter volume in the ventrolateral PFC and OFC and their interdependence. These results document for the first time the importance of gray matter structural integrity of subregions of PFC to the reward-modulated P300 response. PMID:22098260

  14. Emotional Distraction and Bodily Reaction: Modulation of Autonomous Responses by Anodal tDCS to the Prefrontal Cortex.

    PubMed

    Schroeder, Philipp A; Ehlis, Ann-Christine; Wolkenstein, Larissa; Fallgatter, Andreas J; Plewnia, Christian

    2015-01-01

    Prefrontal electric stimulation has been demonstrated to effectively modulate cognitive processing. Specifically, the amelioration of cognitive control (CC) over emotional distraction by transcranial direct current stimulation (tDCS) points toward targeted therapeutic applications in various psychiatric disorders. In addition to behavioral measures, autonomous nervous system (ANS) responses are fundamental bodily signatures of emotional information processing. However, interactions between the modulation of CC by tDCS and ANS responses have received limited attention. We here report on ANS data gathered in healthy subjects that performed an emotional CC task parallel to the modulation of left prefrontal cortical activity by 1 mA anodal or sham tDCS. Skin conductance responses (SCRs) to negative and neutral pictures of human scenes were reduced by anodal as compared to sham tDCS. Individual SCR amplitude variations were associated with the amount of distraction. Moreover, the stimulation-driven performance- and SCR-modulations were related in form of a quadratic, inverse-U function. Thus, our results indicate that non-invasive brain stimulation (i.e., anodal tDCS) can modulate autonomous responses synchronous to behavioral improvements, but the range of possible concurrent improvements from prefrontal stimulation is limited. Interactions between cognitive, affective, neurophysiological, and vegetative responses to emotional content can shape brain stimulation effectiveness and require theory-driven integration in potential treatment protocols.

  15. Differential effects of continuous theta burst stimulation over left premotor cortex and right prefrontal cortex on modulating upper limb somatosensory input.

    PubMed

    Brown, Matt J N; Staines, W Richard

    2016-02-15

    Somatosensory evoked potentials (SEPs) represent somatosensory processing in non-primary motor areas (i.e. frontal N30 and N60) and somatosensory cortices (i.e. parietal P50). It is well-known that the premotor cortex (PMC) and prefrontal cortex (PFC) are involved in the preparation and planning of upper limb movements but it is currently unclear how they modulate somatosensory processing for upper limb motor control. In the current study, two experiments examined SEP modulations after continuous theta burst stimulation (cTBS) was used to transiently disrupt the left PMC (Experiment 1) and right PFC (Experiment 2). Both Experiment 1 (n=15) and Experiment 2 (n=16) used pre-post experimental designs. In both experiments participants performed a task requiring detection of varying amplitudes of attended vibrotactile (VibT) stimuli to the left index finger (D2) and execution of a pre-matched finger sequence with the right (contralateral) hand to specific VibT targets. During the task, SEPs were measured to median nerve (MN) stimulations time-locked during pre-stimulus (250 ms before VibT), early response selection (250 ms after VibT), late preparatory (750 ms after VibT) and execution (1250 ms VibT) phases. The key findings of Experiment 1 revealed significant decreases in N30 and N60 peak amplitudes after cTBS to PMC. In contrast, the results of Experiment 2, also found significant decreased N60 peak amplitudes as well as trends for increased N30 and P50 peak amplitudes. A direct comparison of Experiment 1 and Experiment 2 confirmed differential modulation of N30 peak amplitudes after PMC (gated) compared to PFC (enhanced) cTBS. Collectively, these results support that both the left PMC and right PFC have modulatory roles on early somatosensory input into non-primary motor areas, such as PMC and supplementary motor area (SMA), represented by frontal N30 and N60 SEPs. These results confirm that PMC and PFC are both part of a network that regulates somatosensory input

  16. Relational complexity modulates activity in the prefrontal cortex during numerical inductive reasoning: an fMRI study.

    PubMed

    Feng, Xiao; Peng, Li; Chang-Quan, Long; Yi, Lei; Hong, Li

    2014-09-01

    Most previous studies investigating relational reasoning have used visuo-spatial materials. This fMRI study aimed to determine how relational complexity affects brain activity during inductive reasoning, using numerical materials. Three numerical relational levels of the number series completion task were adopted for use: 0-relational (e.g., "23 23 23"), 1-relational ("32 30 28") and 2-relational ("12 13 15") problems. The fMRI results revealed that the bilateral dorsolateral prefrontal cortex (DLPFC) showed enhanced activity associated with relational complexity. Bilateral inferior parietal lobule (IPL) activity was greater during the 1- and 2-relational level problems than during the 0-relational level problems. In addition, the left fronto-polar cortex (FPC) showed selective activity during the 2-relational level problems. The bilateral DLPFC may be involved in the process of hypothesis generation, whereas the bilateral IPL may be sensitive to calculation demands. Moreover, the sensitivity of the left FPC to the multiple relational problems may be related to the integration of numerical relations. The present study extends our knowledge of the prefrontal activity pattern underlying numerical relational processing. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

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

    PubMed

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

    2008-03-01

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

  19. Space representation in the prefrontal cortex.

    PubMed

    Funahashi, Shintaro

    2013-04-01

    The representation of space and its function in the prefrontal cortex have been examined using a variety of behavioral tasks. Among them, since the delayed-response task requires the temporary maintenance of spatial information, this task has been used to examine the mechanisms of spatial representation. In addition, the concept of working memory to explain prefrontal functions has helped us to understand the nature and functions of space representation in the prefrontal cortex. The detailed analysis of delay-period activity observed in spatial working memory tasks has provided important information for understanding space representation in the prefrontal cortex. Directional delay-period activity has been shown to be a neural correlate of the mechanism for temporarily maintaining information and represent spatial information for the visual cue and the saccade. In addition, many task-related prefrontal neurons exhibit spatially selective activities. These neurons are also important components of spatial information processing. In fact, information flow from sensory-related neurons to motor-related neurons has been demonstrated, along with a change in spatial representation as the trial progresses. The dynamic functional interactions among neurons exhibiting different task-related activities and representing different aspects of information could play an essential role in information processing. In addition, information provided from other cortical or subcortical areas might also be necessary for the representation of space in the prefrontal cortex. To better understand the representation of space and its function in the prefrontal cortex, we need to understand the nature of functional interactions between the prefrontal cortex and other cortical and subcortical areas.

  20. Dopamine modulation of learning and memory in the prefrontal cortex: insights from studies in primates, rodents, and birds

    PubMed Central

    Puig, M. Victoria; Rose, Jonas; Schmidt, Robert; Freund, Nadja

    2014-01-01

    In this review, we provide a brief overview over the current knowledge about the role of dopamine transmission in the prefrontal cortex during learning and memory. We discuss work in humans, monkeys, rats, and birds in order to provide a basis for comparison across species that might help identify crucial features and constraints of the dopaminergic system in executive function. Computational models of dopamine function are introduced to provide a framework for such a comparison. We also provide a brief evolutionary perspective showing that the dopaminergic system is highly preserved across mammals. Even birds, following a largely independent evolution of higher cognitive abilities, have evolved a comparable dopaminergic system. Finally, we discuss the unique advantages and challenges of using different animal models for advancing our understanding of dopamine function in the healthy and diseased brain. PMID:25140130

  1. Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion

    PubMed Central

    Larrieu, T; Hilal, L M; Fourrier, C; De Smedt-Peyrusse, V; Sans N; Capuron, L; Layé, S

    2014-01-01

    Understanding how malnutrition contributes to depression is building momentum. In the present study we unravel molecular and cellular mechanisms by which nutritional disturbances lead to impaired emotional behaviour in mice. Here we report that nutritional n-3 polyunsaturated fatty acids (PUFA) deficiency induces a chronic stress state reflected by disrupted glucocorticoid receptor (GR)-mediated signalling pathway along with hypothalamic–pituitary–adrenal (HPA) axis hyperactivity. This hyperactivity in turn resulted in neuronal atrophy in the dorsolateral (dl)- and dorsomedial (dm)- prefrontal cortex (PFC) and subsequent mood-related behaviour alterations, similarly to chronic social defeat stress. Supplementation of n-3 PUFA prevented detrimental chronic social defeat stress-induced emotional and neuronal impairments by impeding HPA axis hyperactivity. These results indicate a role for dietary n-3 PUFA in the prevention of HPA axis dysfunction associated with the development of some neuropsychiatric disorders including depression. PMID:25203168

  2. Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex

    PubMed Central

    Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Cipolotti, Lisa; Oliveri, Massimiliano

    2015-01-01

    Objective The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task. Method 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS. Results Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance. Conclusion Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects. PMID:26679936

  3. Modulating the Activity of Ventromedial Prefrontal Cortex by Anodal tDCS Enhances the Trustee’s Repayment through Altruism

    PubMed Central

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

    2016-01-01

    Trust and trustworthiness are essential to an efficient economy and play crucial roles in social life. Previous evidence from behavioral experiments has revealed that the trustworthiness of individuals is closely related with their altruistic preference. It has been demonstrated that the ventromedial prefrontal cortex (vmPFC) is associated with decisions involving trustworthiness. Moreover, vmPFC lesion patients showed less trustworthiness and altruism than control subjects, indicating the indispensable role of this specific brain area in human social interactions. However, the causal relationship between this neural area and trustworthiness, as well as altruism, has not been fully revealed. The potential neural basis behind the behavior of trustees’ repayment has also seldom been discussed. In the present study, we aimed to provide evidence of a direct link between the neural and behavioral results through the application of transcranial direct current stimulation (tDCS) over the vmPFC of our participants. We found that activating the vmPFC could promote both the trustworthiness and altruism of our participants. We also show that enhancing the excitability of the vmPFC using tDCS increased the trustworthiness of the participants, and this promoting effect might be attributable to the enhancement of individuals’ altruistic preference. In addition, we revealed that the enhancing effect in trustworthiness and altruism might be specific to the activation of the vmPFC by applying tDCS over another brain region within the prefrontal cortex as a control site. Crucially, our findings provide direct evidence supporting the critical role of the vmPFC in cooperative behaviors in economic interactions, especially the trustees’ repayment in the trust game and the dictators’ altruistic transfer in the dictator game. PMID:27713721

  4. Task-related modulation of effective connectivity during perceptual decision making: dissociation between dorsal and ventral prefrontal cortex.

    PubMed

    Akaishi, Rei; Ueda, Naoko; Sakai, Katsuyuki

    2013-01-01

    The dorsal and ventral parts of the lateral prefrontal cortex have been thought to play distinct roles in decision making. Although its dorsal part such as the frontal eye field (FEF) is shown to play roles in accumulation of sensory information during perceptual decision making, the role of the ventral prefrontal cortex (PFv) is not well-documented. Previous studies have suggested that the PFv is involved in selective attention to the task-relevant information and is associated with accuracy of the behavioral performance. It is unknown, however, whether the accumulation and selection processes are anatomically dissociated between the FEF and PFv. Here we show that, by using concurrent TMS and EEG recording, the short-latency (20-40 ms) TMS-evoked potentials after stimulation of the FEF change as a function of the time to behavioral response, whereas those after stimulation of the PFv change depending on whether the response is correct or not. The potentials after stimulation of either region did not show significant interaction between time to response and performance accuracy, suggesting dissociation between the processes subserved by the FEF and PFv networks. The results are consistent with the idea that the network involving the FEF plays a role in information accumulation, whereas the network involving the PFv plays a role in selecting task relevant information. In addition, stimulation of the FEF and PFv induced activation in common regions in the dorsolateral and medial frontal cortices, suggesting convergence of information processed in the two regions. Taken together, the results suggest dissociation between the FEF and PFv networks for their computational roles in perceptual decision making. The study also highlights the advantage of TMS-EEG technique in investigating the computational processes subserved by the neural network in the human brain with a high temporal resolution.

  5. Neuronal Modulation in the Prefrontal Cortex in a Transitive Inference Task: Evidence of Neuronal Correlates of Mental Schema Management.

    PubMed

    Brunamonti, Emiliano; Mione, Valentina; Di Bello, Fabio; Pani, Pierpaolo; Genovesio, Aldo; Ferraina, Stefano

    2016-01-27

    When informed that A > B and B > C, humans and other animals can easily conclude that A > C. This remarkable trait of advanced animals, which allows them to manipulate knowledge flexibly to infer logical relations, has only recently garnered interest in mainstream neuroscience. How the brain controls these logical processes remains an unanswered question that has been merely superficially addressed in neuroimaging and lesion studies, which are unable to identify the underlying neuronal computations. We observed that the activation pattern of neurons in the prefrontal cortex (PFC) during pair comparisons in a highly demanding transitive inference task fully supports the behavioral performance of the two monkeys that we tested. Our results indicate that the PFC contributes to the construction and use of a mental schema to represent premises. This evidence provides a novel framework for understanding the function of various areas of brain in logic processes and impairments to them in degenerative, traumatic, and psychiatric pathologies. In cognitive neuroscience, it is unknown how information that leads to inferential deductions are encoded and manipulated at the neuronal level. We addressed this question by recording single-unit activity from the dorsolateral prefrontal cortex of monkeys that were performing a transitive inference (TI) task. The TI required one to choose the higher ranked of two items, based on previous, indirect experience. Our results demonstrated that single-neuron activity supports the construction of an abstract, mental schema of ordered items in solving the task and that this representation is independent of the reward value that is experienced for the single items. These findings identify the neural substrates of abstract mental representations that support inferential thinking. Copyright © 2016 the authors 0270-6474/16/361223-14$15.00/0.

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

    PubMed

    Aznar, Susana; Klein, Anders B

    2013-12-01

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

  7. Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

    ERIC Educational Resources Information Center

    Cruse, Damian; Wilding, Edward L.

    2009-01-01

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

  8. Prefrontal Cortex Contributions to Episodic Retrieval Monitoring and Evaluation

    ERIC Educational Resources Information Center

    Cruse, Damian; Wilding, Edward L.

    2009-01-01

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

  9. Aging, self-referencing, and medial prefrontal cortex.

    PubMed

    Gutchess, Angela H; Kensinger, Elizabeth A; Schacter, Daniel L

    2007-01-01

    The lateral prefrontal cortex undergoes both structural and functional changes with healthy aging. In contrast, there is little structural change in the medial prefrontal cortex, but relatively little is known about the functional changes to this region with age. Using an event-related fMRI design, we investigated the response of medial prefrontal cortex during self-referencing in order to compare age groups on a task that young and elderly perform similarly and that is known to actively engage the region in young adults. Nineteen young (M age = 23) and seventeen elderly (M age = 72) judged whether adjectives described themselves, another person, or were presented in upper case. We assessed the overlap in activations between young and elderly for the self-reference effect (self vs. other person), and found that both groups engage medial prefrontal cortex and mid-cingulate during self-referencing. The only cerebral differences between the groups in self versus other personality assessment were found in somatosensory and motor-related areas. In contrast, age-related modulations were found in the cerebral network recruited for emotional valence processing. Elderly (but not young) showed increased activity in the dorsal prefrontal cortex for positive relative to negative items, which could reflect an increase in controlled processing of positive information for elderly adults.

  10. Working Memory in the Prefrontal Cortex

    PubMed Central

    Funahashi, Shintaro

    2017-01-01

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

  11. Working Memory in the Prefrontal Cortex.

    PubMed

    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.

  12. Putting race in context: social class modulates processing of race in the ventromedial prefrontal cortex and amygdala

    PubMed Central

    Hitlin, Steven; Magnotta, Vincent; Tranel, Daniel

    2017-01-01

    Abstract A growing body of literature demonstrates that racial group membership can influence neural responses, e.g. when individuals perceive or interact with persons of another race. However, little attention has been paid to social class, a factor that interacts with racial inequalities in American society. We extend previous literature on race-related neural activity by focusing on how the human brain responds to racial out-groups cast in positively valued social class positions vs less valued ones. We predicted that the ventromedial prefrontal cortex (vmPFC) and the amygdala would have functionally dissociable roles, with the vmPFC playing a more significant role within socially valued in-groups (i.e. the middle-class) and the amygdala having a more crucial role for socially ambivalent and threatening categories (i.e. upper and lower class). We tested these predictions with two complementary studies: (i) a neuropsychological experiment with patients with the vmPFC or amygdala lesions, contrasted with brain damaged and normal comparison participants, and (ii) a functional magnetic resonance imaging experiment with 15 healthy adults. Our findings suggest that two distinct mechanisms underlie class-based racial evaluations, one engaging the vmPFC for positively identified in-group class and another recruiting the amygdala for the class groups that are marginalized or perceived as potential threats. PMID:28398590

  13. Putting race in context: social class modulates processing of race in the ventromedial prefrontal cortex and amygdala.

    PubMed

    Firat, Rengin B; Hitlin, Steven; Magnotta, Vincent; Tranel, Daniel

    2017-08-01

    A growing body of literature demonstrates that racial group membership can influence neural responses, e.g. when individuals perceive or interact with persons of another race. However, little attention has been paid to social class, a factor that interacts with racial inequalities in American society. We extend previous literature on race-related neural activity by focusing on how the human brain responds to racial out-groups cast in positively valued social class positions vs less valued ones. We predicted that the ventromedial prefrontal cortex (vmPFC) and the amygdala would have functionally dissociable roles, with the vmPFC playing a more significant role within socially valued in-groups (i.e. the middle-class) and the amygdala having a more crucial role for socially ambivalent and threatening categories (i.e. upper and lower class). We tested these predictions with two complementary studies: (i) a neuropsychological experiment with patients with the vmPFC or amygdala lesions, contrasted with brain damaged and normal comparison participants, and (ii) a functional magnetic resonance imaging experiment with 15 healthy adults. Our findings suggest that two distinct mechanisms underlie class-based racial evaluations, one engaging the vmPFC for positively identified in-group class and another recruiting the amygdala for the class groups that are marginalized or perceived as potential threats. © The Author (2017). Published by Oxford University Press.

  14. Developmental Outcomes after Early Prefrontal Cortex Damage

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  15. Bilinearity, Rules, and Prefrontal Cortex

    PubMed Central

    Dayan, Peter

    2007-01-01

    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. PMID:18946523

  16. Increasing generosity by disrupting prefrontal cortex.

    PubMed

    Christov-Moore, Leonardo; Sugiyama, Taisei; Grigaityte, Kristina; Iacoboni, Marco

    2017-04-01

    Recent research suggests that prosocial outcomes in sharing games arise from prefrontal control of self-maximizing impulses. We used continuous theta burst stimulation (cTBS) to disrupt the functioning of two prefrontal areas, the right dorsolateral prefrontal cortex (DLPFC) and the dorsomedial prefrontal cortex (DMPFC). We used cTBS in the right MT/V5, as a control area. We then tested subjects' prosocial inclinations with an unsupervised Dictator Game in which they allocated real money anonymously between themselves and low and high socioeconomic status (SES) players. cTBS over the two prefrontal sites made subjects more generous compared to MT/V5. More specifically, cTBS over DLPFC increased offers to high-SES players, while cTBS over DMPFC caused increased offers to low-SES players. These data, the first to demonstrate an effect of disruptive neuromodulation on costly sharing, suggest that DLPFC and MPFC exert inhibitory control over prosocial inclinations during costly sharing, though they may do so in different ways. DLPFC may implement contextual control, while DMPFC may implement a tonic form of control. This study demonstrates that humans' prepotent inclination is toward prosocial outcomes when cognitive control is reduced, even when prosocial decisions carry no strategic benefit and concerns for reputation are minimized.

  17. Modulation of hippocampus-prefrontal cortex synaptic transmission and disruption of executive cognitive functions by MK-801.

    PubMed

    Blot, Kevin; Kimura, Shin-Ichi; Bai, Jing; Kemp, Anne; Manahan-Vaughan, Denise; Giros, Bruno; Tzavara, Eleni; Otani, Satoru

    2015-05-01

    Noncompetitive N-methyl-d-aspartate receptor antagonists such as phencyclidine and MK-801 are known to impair cognitive function in rodents and humans, and serve as a useful tool to study the cellular basis for pathogenesis of schizophrenia cognitive symptoms. In the present study, we tested in rats the effect of MK-801 on ventral hippocampus (HPC)-medial prefrontal cortex (mPFC) synaptic transmission and the performance in 2 cognitive tasks. We found that single injection of MK-801 (0.1 mg/kg) induced gradual and long-lasting increases of the HPC-mPFC response, which shares the common expression mechanisms with long-term potentiation (LTP). But unlike LTP, its induction required no enhanced or synchronized synaptic inputs, suggesting aberrant characteristics. In parallel, rats injected with MK-801 showed impairments of mPFC-dependent cognitive flexibility and HPC-mPFC pathway-dependent spatial working memory. The effects of MK-801 on HPC-mPFC responses and spatial working memory decayed in parallel within 24 h. Moreover, the therapeutically important subtype 2/3 metabotropic glutamate receptor agonist LY379268, which blocked MK-801-induced potentiation, ameliorated the MK-801-induced impairment of spatial working memory. Our results show a novel form of use-independent long-lasting potentiation in HPC-mPFC pathway induced by MK-801, which is associated with impairment of HPC-mPFC projection-dependent cognitive function. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Functional lateralization of the medial prefrontal cortex in the modulation of anxiety in mice: Left or right?

    PubMed

    Costa, N S; Vicente, M A; Cipriano, A C; Miguel, T T; Nunes-de-Souza, R L

    2016-09-01

    It has been suggested that the left medial prefrontal cortex (LmPFC) has an inhibitory role in controlling the right mPFC (RmPFC), thereby reducing the deleterious effects of stressors on emotional states. Here, we investigated the effects on anxiety of bilateral or unilateral injections of NOC-9 [a nitric oxide (NO) donor] and cobalt chloride (CoCl2; a synaptic inhibitor) into the mPFC of mice exposed to the elevated plus-maze (Experiments 1 and 2). The effects of restraint or social defeat on anxiety in undrugged mice were recorded at 5 min or 24 h after exposure to the stress (Experiment 3). Experiment 4 investigated the effects of LmPFC injection of CoCl2 combined with restraint or social defeat on anxiety, which was recorded 24 h later. Although intra-RmPFC NOC-9 produced anxiogenesis, its injection into the LmPFC, or bilaterally, did not change anxiety. Intra-RmPFC or -LmPFC injection of CoCl2 produced anxiolytic- and anxiogenic-like effects, respectively. Both restraint and social defeat produced anxiogenesis at 5 min, but defeated mice did not display anxiety 24 h after the stress. Although intra-LmPFC CoCl2 did not change anxiety, which was recorded 24 h later in non-stressed mice, this synaptic inhibitor produced a clear, anxiogenic-like effect in defeated (but not restrained) mice. These results suggest that (i) nitrergic activation of the RmPFC increases anxiety, which in turn is inhibited by NO production within the LmPFC; (ii) neuronal inhibition of the RmPFC or LmPFC elicits anxiolysis and anxiogenesis, respectively; and (iii) inactivation of the LmPFC results in recrudescence of anxiety induced by social defeat stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Dopaminergic modulation of short-term synaptic plasticity in fast-spiking interneurons of primate dorsolateral prefrontal cortex.

    PubMed

    Gonzalez-Burgos, G; Kroener, S; Seamans, J K; Lewis, D A; Barrionuevo, G

    2005-12-01

    Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term excitatory postsynaptic potential (EPSP) depression. The D1 receptor agonist SKF81297 (5 microM) significantly reduced the amplitude of the first EPSP but not of subsequent responses in EPSP trains, which still displayed significant depression. Dopamine (DA; 10 microM) effects were similar to those of SKF81297 and were abolished by the D1 antagonist SCH23390 (5 microM), indicating a D1 receptor-mediated effect. DA did not alter miniature excitatory postsynaptic currents, suggesting that its effects were activity dependent and presynaptic action potential dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells, contribution of N-methyl-D-aspartate receptors to EPSPs at subthreshold potentials was not significant and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 s suggests that in fast-spiking neurons, DA reduces the amplitude of EPSPs evoked at low frequency but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spike-timing-dependent temporal codes contained in presynaptic spike trains. Thus DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.

  20. Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex

    PubMed Central

    Counotte, Danielle S.; Goriounova, Natalia A.; Moretti, Milena; Smoluch, Marek T.; Irth, Hubertus; Clementi, Francesco; Schoffelmeer, Anton N. M.; Mansvelder, Huibert D.; Smit, August B.; Gotti, Cecilia; Spijker, Sabine

    2013-01-01

    Adolescence is a critical developmental period during which most adult smokers initiate their habit. Adolescents are more vulnerable than adults to nicotine’s long-term effects on addictive and cognitive behavior. We investigated whether adolescent nicotine exposure in rats modifies expression of nicotinic acetylcholine receptors (nAChRs) in medial prefrontal cortex (mPFC) in the short and/or long term, and whether this has functional consequences. Using receptor binding studies followed by immunoprecipitation of nAChR subunits, we showed that adolescent nicotine exposure, as compared with saline, caused an increase in mPFC nAChRs containing α4 or β2 subunits (24 and 18%, respectively) 24 h after the last injection. Nicotine exposure in adulthood had no such effect. This increase was transient and was not observed 5 wk following either adolescent or adult nicotine exposure. In line with increased nAChRs expression 1 d after adolescent nicotine exposure, we observed a 34% increase in amplitude of nicotine-induced spontaneous inhibitory postsynaptic currents in layer II/III mPFC pyramidal neurons. These effects were transient and specific, and observed only acutely after adolescent nicotine exposure, but not after 5 wk, and no changes were observed in adult-exposed animals. The acute nicotine-induced increase in α4β2-containing receptors in adolescents interferes with the normal developmental decrease (37%) of these receptors from early adolescence (postnatal day 34) to adulthood (postnatal day 104) in the mPFC. Together, this suggests that these receptors play a role in mediating the acute rewarding effects of nicotine and may underlie the increased sensitivity of adolescents to nicotine. PMID:22308197

  1. Neurotensin modulation of acetylcholine, GABA, and aspartate release from rat prefrontal cortex studied in vivo with microdialysis.

    PubMed

    Petkova-Kirova, Polina; Rakovska, Angelina; Della Corte, Laura; Zaekova, Galina; Radomirov, Radomir; Mayer, Aliz

    2008-09-30

    The effects of the peptide transmitter neurotensin (NT) on the release of acetylcholine (ACh), gamma-aminobutyric acid (GABA), glutamate (Glu), aspartate (Asp), and taurine from the prefrontal cortex (PFC) of freely moving rats were studied by transversal microdialysis. Neurotensin (0.2 and 1 microM) administered locally in the PFC produced a concentration-dependent increase in the extracellular levels of ACh, GABA, and Asp, but not of Glu or taurine. The increase produced by 1 microM NT reached a maximum of about 240% for ACh, 370% for GABA, and 380% for Asp. Lower doses of NT (0.05 microM) did not cause a significant change in ACh, GABA, or Asp output in the PFC. Higher concentrations of NT (2 microM) did not induce further increases in the level of neurotransmitters. A high-affinity selective neurotensin receptor (NTR1) antagonist SR 48692 (0.5 microM) perfused locally blocked neurotensin (1 microM)-evoked ACh, GABA, and Asp release. Local infusion of the sodium channel blocker tetrodotoxin (TTX) (1 microM) decreased the release of ACh, had no significant effect on GABA or Asp release, and prevented the 1 microM neurotensin-induced increase in ACh, GABA, and Asp output. Removal of calcium from the Ringer's solution prevented the peptide from having any effects on the neurotransmitters. Thus, in vivo NT plays a modulatory role in the PFC by interacting with cortical neurons releasing GABA and Asp and with ACh-containing neurons projecting to the PFC. The NT effects are of neural origin, as they are TTX-sensitive, and mediated by the NTR1 receptor, as they are antagonized by SR 48692.

  2. Modulating the interference effect on spatial working memory by applying transcranial direct current stimulation over the right dorsolateral prefrontal cortex.

    PubMed

    Wu, Yi-Jen; Tseng, Philip; Chang, Chi-Fu; Pai, Ming-Chyi; Hsu, Kuei-Sen; Lin, Chou-Ching; Juan, Chi-Hung

    2014-11-01

    Spatial working memory (SWM) is the ability to temporarily store and manipulate spatial information. It has a limited capacity and is quite vulnerable to interference. Dorsolateral prefrontal cortex (DLPFC) has been shown to be a part of the SWM network but its specific functional role still remains unknown. Here we applied transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique that provides polarity-specific stimulation over the targeted region, to investigate the specific role of the right DLPFC in resolving interference in SWM. A forward- and backward-recall computerized Corsi Block Tapping task (CBT), both with and without a concurrent motor interference task (the modified Luria manual sequencing task) was used to measure SWM capacity and reaction time. The results showed that motor interference impeded accuracy and prolonged reaction time in forward and backward recall for SWM. Anodal tDCS over right DLPFC yielded the tendency to shorten participants' reaction time in the conditions with interference (forward with interference, and backward with interference). Most importantly, anodal tDCS significantly improved participants' SWM span when cognitive demand was the highest (the "backward-recall with motor interference" condition). These results suggest that (1) the right DLPFC plays a crucial role in dealing with the cross-domain motor interference for spatial working memory and (2) the anodal tDCS over right DLPFC improved SWM capacity particularly when task difficulty demands more complex mental manipulations that could be due to the facilitatory effect of anodal tDCS which enhanced the DLPFC function within central executive system at the top-down attentional level.

  3. Human prefrontal cortex: evolution, development, and pathology.

    PubMed

    Teffer, Kate; Semendeferi, Katerina

    2012-01-01

    The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.

  4. [Psychopathy and neuropsychology of the prefrontal cortex].

    PubMed

    Jurado, M A; Junqué, C

    1996-01-01

    We review the main experimental works about the relationship between psychopathy and prefrontal cortex. First neuropsychological articles found contradictory results exploring psychopaths who were diagnosed by different criteria and using putative dorsolateral tests. Attentional deficits in psychopaths and relationships between psychopathy and attention disorder with and without hyperactivity have been studied. Distinction between primary and secondary psychopathy has been related to neuropsychological impairment in antisocial disorder. Differentiation between orbital and dorsolateral prefrontal systems should be taken into account in order to study the neuropsychological deficits in psychopathy. It has been pointed that orbitoventral system would be involved in antisocial behaviour. Hence, neuropsychological impairment in psychopaths is expected to be related to orbitofrontal dysfunction.

  5. Doping the Mind: Dopaminergic Modulation of Prefrontal Cortical Cognition.

    PubMed

    Ranganath, Ajit; Jacob, Simon N

    2016-12-01

    The prefrontal cortex is the center of cognitive control. Processing in prefrontal cortical circuits enables us to direct attention to behaviorally relevant events; to memorize, structure, and categorize information; and to learn new concepts. The prefrontal cortex receives strong projections from midbrain neurons that use dopamine as a transmitter. In this article, we review the crucial role dopamine plays as a modulator of prefrontal cognitive functions, in the primate brain in particular. Following a summary of the anatomy and physiology of the midbrain dopamine system, we focus on recent studies that investigated dopaminergic effects in prefrontal cortex at the cellular level. We then discuss how unregulated prefrontal dopamine signaling could contribute to major disorders of cognition. The studies highlighted in this review demonstrate the powerful influence dopamine exerts on the mind.

  6. Dopamine modulation of GABAergic function enables network stability and input selectivity for sustaining working memory in a computational model of the prefrontal cortex.

    PubMed

    Lew, Sergio E; Tseng, Kuei Y

    2014-12-01

    Dopamine modulation of GABAergic transmission in the prefrontal cortex (PFC) is thought to be critical for sustaining cognitive processes such as working memory and decision-making. Here, we developed a neurocomputational model of the PFC that includes physiological features of the facilitatory action of dopamine on fast-spiking interneurons to assess how a GABAergic dysregulation impacts on the prefrontal network stability and working memory. We found that a particular non-linear relationship between dopamine transmission and GABA function is required to enable input selectivity in the PFC for the formation and retention of working memory. Either degradation of the dopamine signal or the GABAergic function is sufficient to elicit hyperexcitability in pyramidal neurons and working memory impairments. The simulations also revealed an inverted U-shape relationship between working memory and dopamine, a function that is maintained even at high levels of GABA degradation. In fact, the working memory deficits resulting from reduced GABAergic transmission can be rescued by increasing dopamine tone and vice versa. We also examined the role of this dopamine-GABA interaction for the termination of working memory and found that the extent of GABAergic excitation needed to reset the PFC network begins to occur when the activity of fast-spiking interneurons surpasses 40 Hz. Together, these results indicate that the capability of the PFC to sustain working memory and network stability depends on a robust interplay of compensatory mechanisms between dopamine tone and the activity of local GABAergic interneurons.

  7. Dopamine Modulation of GABAergic Function Enables Network Stability and Input Selectivity for Sustaining Working Memory in a Computational Model of the Prefrontal Cortex

    PubMed Central

    Lew, Sergio E; Tseng, Kuei Y

    2014-01-01

    Dopamine modulation of GABAergic transmission in the prefrontal cortex (PFC) is thought to be critical for sustaining cognitive processes such as working memory and decision-making. Here, we developed a neurocomputational model of the PFC that includes physiological features of the facilitatory action of dopamine on fast-spiking interneurons to assess how a GABAergic dysregulation impacts on the prefrontal network stability and working memory. We found that a particular non-linear relationship between dopamine transmission and GABA function is required to enable input selectivity in the PFC for the formation and retention of working memory. Either degradation of the dopamine signal or the GABAergic function is sufficient to elicit hyperexcitability in pyramidal neurons and working memory impairments. The simulations also revealed an inverted U-shape relationship between working memory and dopamine, a function that is maintained even at high levels of GABA degradation. In fact, the working memory deficits resulting from reduced GABAergic transmission can be rescued by increasing dopamine tone and vice versa. We also examined the role of this dopamine–GABA interaction for the termination of working memory and found that the extent of GABAergic excitation needed to reset the PFC network begins to occur when the activity of fast-spiking interneurons surpasses 40 Hz. Together, these results indicate that the capability of the PFC to sustain working memory and network stability depends on a robust interplay of compensatory mechanisms between dopamine tone and the activity of local GABAergic interneurons. PMID:24975022

  8. Theta oscillations in the medial prefrontal cortex are modulated by spatial working memory and synchronize with the hippocampus through its ventral subregion.

    PubMed

    O'Neill, Pia-Kelsey; Gordon, Joshua A; Sigurdsson, Torfi

    2013-08-28

    The rodent medial prefrontal cortex (mPFC) is critical for spatial working memory (SWM), but the underlying neural processes are incompletely understood. During SWM tasks, neural activity in the mPFC becomes synchronized with theta oscillations in the hippocampus, and the strength of hippocampal-prefrontal synchrony is correlated with behavioral performance. However, to what extent the mPFC generates theta oscillations and whether they are also modulated by SWM remains unclear. Furthermore, it is not known how theta oscillations in the mPFC are synchronized with theta oscillations in the hippocampus. Although the ventral hippocampus (vHPC) projects directly to the mPFC, previous studies have only examined synchrony between the mPFC and the dorsal hippocampus (dHPC), with which it is not directly connected. To address these issues, we recorded simultaneously from the dHPC, vHPC, and mPFC of mice performing a SWM task in a T-maze. The local field potential recorded in the mPFC displayed robust theta oscillations that were reflected in local measures of neuronal activity and modulated by SWM performance. mPFC theta oscillations were also synchronized with theta oscillations in both the vHPC and dHPC, and the magnitude of theta synchrony was modulated by SWM. Removing the influence of the vHPC either computationally (through partial correlations) or experimentally (through pharmacological inactivation) reduced theta synchrony between the mPFC and dHPC. These results reveal theta oscillations as a prominent feature of neural activity in the mPFC and a candidate neural mechanism underlying SWM. Furthermore, our results suggest that the vHPC plays a major role in synchronizing theta oscillations in the mPFC and the hippocampus.

  9. The role of prefrontal cortex in psychopathy

    PubMed Central

    Koenigs, Michael

    2014-01-01

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

  10. CB-1 receptors modulate the effect of the selective serotonin reuptake inhibitor, citalopram on extracellular serotonin levels in the rat prefrontal cortex.

    PubMed

    Kleijn, Jelle; Cremers, Thomas I F H; Hofland, Corry M; Westerink, Ben H C

    2011-07-01

    A large percentage of depressed individuals use drugs of abuse, like cannabis. This study investigates the impact of cannabis on the pharmacological effects of the antidepressant citalopram. Using microdialysis in the prefrontal cortex of rats we monitored serotonin levels before and after cannabinoid (WIN55,212-2 or rimonabant) and citalopram administration. Stimulating CB-1 decreased the effect of citalopram on increasing serotonin levels in the prefrontal cortex. Blocking CB-1 augmented this effect of citalopram. Although repeating these experiments in a chronical setting is recommended the present results might have implication for the clinical effects of citalopram.

  11. Dopamine D4 receptor transmission in the prefrontal cortex controls the salience of emotional memory via modulation of calcium calmodulin-dependent kinase II.

    PubMed

    Lauzon, Nicole M; Ahmad, Tasha; Laviolette, Steven R

    2012-11-01

    Dopamine (DA) signaling in the medial prefrontal cortex (mPFC) plays a critical role in the processing of emotional information and memory encoding. Activation of DA D4 receptors within the prelimbic (PLC) division of the mPFC bidirectionally modulates emotional memory by strongly potentiating the salience of normally nonsalient emotional memories but blocking the acquisition of suprathreshold emotionally salient fear memories. Previous in vitro studies have shown that activation of cortical DA D4 receptors can bidirectionally modulate levels of α-calcium calmodulin-dependent kinase II (α-CaMKII), a molecule essential for learning and memory. Using an olfactory fear conditioning procedure in rats combined with microinfusions into the mPFC, we examined the potential role of D4 receptor-mediated control of emotional memory salience through signaling via CaMKII, cAMP/protein kinase A (PKA), and protein phosphatase-1 (PP1) signaling. We report that CaMKII blockade prevents the ability of intra-mPFC DA D4 receptor activation to potentiate the salience of subthreshold fear memory. In contrast, blockade of either cAMP/PKA or PP1 signaling pathways rescued the blockade of suprathreshold fear memory via intra-mPFC D4 receptor activation. Our results demonstrate that modulation of emotional memory salience via intra-mPFC DA D4 receptor transmission depends upon downstream signaling via CaMKII, cAMP/PKA, and PP1 substrates.

  12. Maternal high-fat diet and early life stress differentially modulate spine density and dendritic morphology in the medial prefrontal cortex of juvenile and adult rats.

    PubMed

    Rincel, Marion; Lépinay, Amandine L; Janthakhin, Yoottana; Soudain, Gwenaëlle; Yvon, Sophie; Da Silva, Stéphanie; Joffre, Corinne; Aubert, Agnès; Séré, Alexandra; Layé, Sophie; Theodorou, Vassilia; Ferreira, Guillaume; Darnaudéry, Muriel

    2017-10-11

    The medial prefrontal cortex (mPFC) is a key area for the regulation of numerous brain functions including stress response and cognitive processes. This brain area is also particularly affected by adversity during early life. Using an animal model in rats, we recently demonstrated that maternal exposure to a high-fat diet (HFD) prevents maternal separation (MS)-induced gene expression alterations in the developing PFC and attenuates several long-term deleterious behavioral effects of MS. In the present study, we ask whether maternal HFD could protect mPFC neurons of pups exposed to early life stress by examining dendritic morphology and spine density in juvenile [postnatal day (PND) 21] and adult rats submitted to MS. Dams were fed either a control or an HFD throughout gestation and lactation, and pups were submitted to MS from PND2 to PND14. We report that maternal HFD prevents MS-induced spine loss at PND21 and dendritic atrophy at adulthood. Furthermore, we show in adult MS rats that PFC-dependent memory extinction deficits are prevented by maternal HFD. Finally, perinatal HFD exposure reverses gut leakiness following stress in pups and seems to exert an anti-stress effect in dams. Overall, our work demonstrates that maternal HFD affects the developing brain and suggests that nutrition, possibly through gut-brain interactions, could modulate mPFC sensitivity to early stress.

  13. Distinct roles of methamphetamine in modulating spatial memory consolidation, retrieval, reconsolidation and the accompanying changes of ERK and CREB activation in hippocampus and prefrontal cortex.

    PubMed

    Cao, Guofen; Zhu, Jie; Zhong, Qing; Shi, Chaofeng; Dang, Yonghui; Han, Wei; Liu, Xinshe; Xu, Ming; Chen, Teng

    2013-04-01

    Drugs of abuse modulated learning and memory in humans yet the underlying mechanism remained unclear. The extracellular signal-regulated kinase (ERK) and the transcription factor cAMP response element-binding protein (CREB) were involved in neuroplastic changes associated with learning and memory. In the current study, we used a Morris water maze to examine the effect of methamphetamine (METH) on different processes of spatial memory in mice. We then investigated the status of ERK and CREB in the hippocampus and prefrontal cortex (PFC). We found that 1.0 mg/kg dose of METH facilitated spatial memory consolidation when it was injected immediately after the last learning trial. In contrast, the same dose of METH had no effect on spatial memory retrieval when it was injected 30 min before the test. Furthermore, 1.0 mg/kg dose of METH injected immediately after retrieval had no effect on spatial memory reconsolidation. Activation of both ERK and CREB in the hippocampus was found following memory consolidation but not after retrieval or reconsolidation in METH-treated mouse groups. In contrast, activation of both ERK and CREB in the PFC was found following memory retrieval but not other processes in METH-treated mouse groups. These results suggested that METH facilitated spatial memory consolidation but not retrieval or reconsolidation. Moreover, activation of the ERK and CREB signaling pathway in the hippocampus might be involved in METH-induced spatial memory changes.

  14. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    SciTech Connect

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  15. A selective α2 B adrenoceptor agonist (A-1262543) and duloxetine modulate nociceptive neurones in the medial prefrontal cortex, but not in the spinal cord of neuropathic rats.

    PubMed

    Chu, K L; Xu, J; Frost, J; Li, L; Gomez, E; Dart, M J; Jarvis, M F; Meyer, M D; McGaraughty, S

    2015-05-01

    The noradrenergic system contributes to pain modulation, but the roles of its specific adrenoceptors are still being defined. We have identified a novel, potent (rat EC50  = 4.3 nM) and selective α2B receptor agonist, A-1262543, to further explore this adrenoceptor subtype's contribution to pathological nociception. Systemic administration of A-1262543 (1-10 mg/kg, intraperitoneal) dose-dependently attenuated mechanical allodynia in animals with a spinal nerve ligation injury. To further explore its mechanism of action, the activity of nociceptive neurones in the spinal cord and medial prefrontal cortex (mPFC) were examined after injection of 3 mg/kg of A-1262543 (intravenous, i.v.). These effects were compared with duloxetine (3 mg/kg, i.v.), a dual noradrenaline (NA) and serotonin (5-HT) reuptake inhibitor. Systemic administration of A-1262543 or duloxetine did not alter the spontaneous or evoked firing of spinal wide dynamic range and nociceptive-specific neurones in the neuropathic rats, indicating that neither compound engaged spinal, peripheral or descending pathways. In contrast to the lack of effect on spinal neurones, both A-1262543 and duloxetine reduced the evoked and spontaneous firing of 'pain-responsive' (PR) neurones in the mPFC. Duloxetine, but not A-1262543, also inhibited the firing of pain non-responsive (nPR) neurones in the mPFC probably reflecting duloxetine's contribution to modulating non-pain endpoints. These data highlight that activation of the α2B adrenoceptor as well as inhibiting NA and 5-HT reuptake can result in modulating the ascending nociceptive system, and in particular, dampening the firing of PR neurones in the mPFC. © 2014 European Pain Federation - EFIC®

  16. PET neuroimaging of extrastriatal dopamine receptors and prefrontal cortex functions.

    PubMed

    Takahashi, Hidehiko

    2013-12-01

    The role of prefrontal dopamine D1 receptors in prefrontal cortex (PFC) functions, including working memory, is widely investigated. However, human (healthy volunteers and schizophrenia patients) positron emission tomography (PET) studies about the relationship between prefrontal D1 receptors and PFC functions are somewhat inconsistent. We argued that several factors including an inverted U-shaped relationship between prefrontal D1 receptors and PFC functions might be responsible for these inconsistencies. In contrast to D1 receptors, relatively less attention has been paid to the role of D2 receptors in PFC functions. Several animal and human pharmacological studies have reported that the systemic administration of D2 receptor agonist/antagonist modulates PFC functions, although those studies do not tell us which region(s) is responsible for the effect. Furthermore, while prefrontal D1 receptors are primarily involved in working memory, other PFC functions such as set-shifting seem to be differentially modulated by dopamine. PET studies of extrastriatal D2 receptors including ours suggested that orchestration of prefrontal dopamine transmission and hippocampal dopamine transmission might be necessary for a broad range of normal PFC functions. In order to understand the complex effects of dopamine signaling on PFC functions, measuring a single index related to basic dopamine tone is not sufficient. For a better understanding of the meanings of PET indices related to neurotransmitters, comprehensive information (presynaptic, postsynaptic, and beyond receptor signaling) will be required. Still, an interdisciplinary approach combining molecular imaging techniques with cognitive neuroscience and clinical psychiatry will provide new perspectives for understanding the neurobiology of neuropsychiatric disorders and their innovative drug developments.

  17. Predator Exposure/Psychosocial Stress Animal Model of Post-Traumatic Stress Disorder Modulates Neurotransmitters in the Rat Hippocampus and Prefrontal Cortex

    PubMed Central

    Wilson, C. Brad; Ebenezer, Philip J.; McLaughlin, Leslie D.; Francis, Joseph

    2014-01-01

    Post-Traumatic Stress Disorder (PTSD) can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT) may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE), 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), dopamine (DA), and 3,4-Dihydroxyphenylacetic acid (DOPAC), and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC). In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may cause a

  18. Amodal Processing in Human Prefrontal Cortex

    PubMed Central

    Dux, Paul E.; Tombu, Michael N.; Asplund, Christopher L.; Marois, René

    2013-01-01

    Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., “central executive,” Baddeley and Hitch, 1974; “supervisory attentional system,” Norman and Shallice, 1986; “response selection bottleneck,” Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex. PMID:23843526

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  20. Discourse Production Following Injury to the Dorsolateral Prefrontal Cortex

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  2. [Emotional and Motivational Functions of the Prefrontal Cortex].

    PubMed

    Watanabe, Masataka

    2016-11-01

    Patients with the damage to the orbital region of the prefrontal cortex and monkeys with lesions in this area show impairment in emotional and motivational behavior. They also have difficulty in the extinction of learned behavior and in the reversal learning. This brain area is concerned with not only the value estimation of reward and aversive stimuli but also the expectation of these stimuli. The lateral prefrontal cortex plays an important role in the integration of emotion/motivation and cognition. The medial prefrontal cortex is concerned with action selection based on the previous reward history. The ventrolateral prefrontal cortex that comprises the anterior parts of the orbital and inferior medial prefrontal cortex plays an important role in emotion-based decision-making.

  3. Altered connectivity between prefrontal and sensorimotor cortex in conversion paralysis.

    PubMed

    de Lange, Floris P; Toni, Ivan; Roelofs, Karin

    2010-05-01

    Conversion paralysis (CP) is a frequent and impairing psychiatric disorder, affecting voluntary motor function. Yet, we have previously shown that the motor system of CP patients with a unilateral conversion paresis is recruited to a similar degree during imagined movements of the affected and unaffected limb. In contrast, imagery of movements with the affected limb results in larger prefrontal activation. It remains unclear how this hand-specific increased prefrontal activity relates to the reduced responsiveness of motor and somatosensory areas, a consistent and important feature of CP patients. In the current study, we investigated changes in the inter-regional coupling between prefrontal cortex (PFC) and sensorimotor regions when CP patients imagined movements involving either the affected or the unaffected hand. We found that there were distinct connectivity patterns for different parts of the PFC. While ventromedial PFC was not functionally connected to the motor system, we observed strong functional coupling between the dorsolateral PFC and various sensorimotor areas. Furthermore, this coupling was modulated by whether patients imagined movements of their affected or unaffected hand. Together, these results suggest that the reduced motor responsitivity observed in CP may be linked to altered dorsolateral prefrontal-motor connectivity.

  4. Medial prefrontal cortex neuronal circuits in fear behavior.

    PubMed

    Courtin, J; Bienvenu, T C M; Einarsson, E Ö; Herry, C

    2013-06-14

    The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the modulation of fear behavior over the past few decades. Anatomical, functional and electrophysiological studies have begun to shed light on the precise mechanisms by which different prefrontal regions regulate the expression and inhibition of fear behavior. These studies have established a canonical view of mPFC functions during fear behavior with dorsal regions selectively involved in the expression of fear behavior and ventral regions linked to the inhibition of fear behavior. Although numerous reports support this view, recent data have refined this model and suggested that dorsal prefrontal regions might also play an important role in the encoding of fear behavior itself. The recent development of sophisticated approaches such as large scale neuronal recordings, simultaneous multisite recordings of spiking activity and local field potentials (LFPs) along with optogenetic approaches will facilitate the testing of these new hypotheses in the near future. Here we provide an extensive review of the literature on the role of mPFC in fear behavior and propose further directions to dissect the contribution of specific prefrontal neuronal elements and circuits in the regulation of fear behavior. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence

    PubMed Central

    Batista, Edson Kruger; Klauss, Jaisa; Fregni, Felipe; Nitsche, Michael A.

    2015-01-01

    Background: Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction. Methods: We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symtoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4±9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35cm2, for 20 minutes), every other day, and 19 males (mean age 30.3±8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group. Results: Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P=.028) and baseline values (P=.003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P=.047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P=.03), and of the overall perception of quality of life (P=.031) and of health (P=.048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups. Conclusions: Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing

  6. Human lesion studies of ventromedial prefrontal cortex.

    PubMed

    Schneider, Brett; Koenigs, Michael

    2017-09-28

    Studies of neurological patients with focal lesions involving ventromedial prefrontal cortex (vmPFC) have demonstrated a critical role for this brain area in various aspects of cognition, emotion, and behavior. In this article, we review the key themes, methods, and findings from neuropsychological research on vmPFC lesion patients. Early case studies demonstrated profound disruptions in personality and behavior following vmPFC damage, including blunted affect, poor decision-making, and inappropriate social behavior. Subsequent laboratory investigations with groups of vmPFC lesion patients have revealed deficits in a host of interrelated functions, such as value-based decision-making, future and counterfactual thinking, physiological arousal to emotional stimuli, emotion recognition, empathy, moral judgment, and memory confabulation. The compendium of findings described here demonstrates that vmPFC is crucial for diverse aspects of adaptive function. Copyright © 2017. Published by Elsevier Ltd.

  7. Periodontal tactile input activates the prefrontal cortex

    PubMed Central

    Higaki, Nobuaki; Goto, Takaharu; Ichikawa, Tetsuo

    2016-01-01

    The prefrontal cortex (PFC) plays a role in complex cognitive behavioural planning, decision-making, and social behaviours. However, the effects of sensory integration during motor tasks on PFC activation have not been studied to date. Therefore, we investigated the effect of peripheral sensory information and external information on PFC activation using functional near-infrared spectroscopy (fNIRS). Cerebral blood flow (CBF) was increased around bilateral Brodmann areas 46 and 10 during visual and auditory information integration during an occlusal force (biting) task. After local anesthesia, CBF values were significantly decreased, but occlusal force was similar. In conclusion, the effects of peripheral sensory information from the periodontal ligament and external information have minimal impacts on occlusal force maintenance but are important for PFC activation. PMID:27833164

  8. Dynamic neuroplasticity after human prefrontal cortex damage.

    PubMed

    Voytek, Bradley; Davis, Matar; Yago, Elena; Barceló, Francisco; Vogel, Edward K; Knight, Robert T

    2010-11-04

    Memory and attention deficits are common after prefrontal cortex (PFC) damage, yet people generally recover some function over time. Recovery is thought to be dependent upon undamaged brain regions, but the temporal dynamics underlying cognitive recovery are poorly understood. Here, we provide evidence that the intact PFC compensates for damage in the lesioned PFC on a trial-by-trial basis dependent on cognitive load. The extent of this rapid functional compensation is indexed by transient increases in electrophysiological measures of attention and memory in the intact PFC, detectable within a second after stimulus presentation and only when the lesioned hemisphere is challenged. These observations provide evidence supporting a dynamic and flexible model of compensatory neural plasticity.

  9. Ventromedial prefrontal cortex, adding value to autobiographical memories

    PubMed Central

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

    2016-01-01

    The medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants’ memories when they were recalling and evaluating these items. An unrelated modulation by the participant’s familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information, and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories. PMID:27338616

  10. Involvement of CB1 and TRPV1 receptors located in the ventral medial prefrontal cortex in the modulation of stress coping behavior.

    PubMed

    Sartim, A G; Moreira, F A; Joca, S R L

    2017-01-06

    Cannabinoid type-1 (CB1) and transient receptor potential vanilloid type-1 (TRPV1) receptors may have opposite roles in modulating neural activity and, consequently, in regulating the stress response. These receptors are widely expressed in several brain structures, including the ventral medial prefrontal cortex (vmPFC). The functional consequences of the interaction between CB1 and TRPV1, however, have scarcely been explored. Therefore, we investigated if CB1 and TRPV1 receptors located in the vmPFC would be involved in the behavioral changes induced by the stress of the forced swim test (FST). Rats with cannulae implanted into the vmPFC were given the dual blocker of TRPV1 receptors and fatty acid amide hydrolase (FAAH), Arachidonyl serotonin (AA-5HT, 0.125/0.25/0.5nmol), TRPV1 antagonist, SB366791 (0.5/1/10nmol), FAAH inhibitor, URB597 (0.001/0.01/0.1/1nmol), or vehicle and were submitted to the FST, or to the open-field test. Another group received intra-vmPFC injection of SB366791 or vehicle, followed by a second injection of URB597 or vehicle, and was submitted to the FST. Lastly, a group received intra-vmPFC injection of a CB1 antagonist, in sub-effective dose or vehicle, followed by AA-5HT, SB366791 or vehicle. The results showed that AA-5HT, SB366791 and URB597 significantly reduced the immobility time without changing the locomotor activity. Furthermore, the co-administration of URB597 and SB366791 in sub-effective doses induced an antidepressant-like effect in the FST. Additionally, the antidepressant-like effect of AA-5HT was prevented by the CB1 antagonist. Together, these results suggest that both, CB1 and TRPV1 receptors located in the vmPFC are involved in the behavioral responses to stress, although in opposite ways.

  11. Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits.

    PubMed

    Rossignoli, Matheus Teixeira; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Do Val da Silva, Raquel Araujo; Bueno-Junior, Lezio Soares; Kandratavicius, Ludmyla; Peixoto-Santos, José Eduardo; Crippa, José Alexandre; Cecilio Hallak, Jaime Eduardo; Zuardi, Antonio Waldo; Szawka, Raphael Escorsim; Anselmo-Franci, Janete; Leite, João Pereira; Romcy-Pereira, Rodrigo Neves

    2017-03-24

    The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits.

  12. Divergent Plasticity of Prefrontal Cortex Networks

    PubMed Central

    Moghaddam, Bita; Homayoun, Houman

    2010-01-01

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

  13. A GABAergic Projection from the Centromedial Nuclei of the Amygdala to Ventromedial Prefrontal Cortex Modulates Reward Behavior.

    PubMed

    Seo, Dong-Oh; Funderburk, Samuel C; Bhatti, Dionnet L; Motard, Laura E; Newbold, Dillan; Girven, Kasey S; McCall, Jordan G; Krashes, Michael; Sparta, Dennis R; Bruchas, Michael R

    2016-10-19

    The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors. However, the CeMA and ventromedial PFC (vmPFC) interaction in reward regulation remains poorly understood. Here, we identify and dissect a GABAergic projection that originates in the CeMA and terminates in the vmPFC (VGat-Cre(CeMA-vmPFC)) using viral-vector-mediated, cell-type-specific optogenetic techniques in mice. Pathway-specific optogenetic activation of the VGat-Cre(CeMA-vmPFC) circuit in awake, behaving animals produced a positive, reward-like phenotype in real-time place preference and increased locomotor activity in open-field testing. In sucrose operant conditioning, the photoactivation of these terminals increased nose-poking effort with no effect on licking behavior and robustly facilitated the extinction of operant behavior. However, photoactivation of these terminals did not induce self-stimulation in the absence of an external reward. The results described here suggest that the VGat-Cre(CeMA-vmPFC) projection acts to modulate existing reward-related behaviors.

  14. Social state representation in prefrontal cortex.

    PubMed

    Fujii, Naotaka; Hihara, Sayaka; Nagasaka, Yasuo; Iriki, Atsushi

    2009-01-01

    One of the cardinal mental faculties of humans and other primates is social brain function, the collective name assigned to the distributed system of social cognitive processes that orchestrate our sophisticated adaptive social behavior. These must include processes for recognizing current social context and maintaining an internal representation of the current social state as a reference for decision-making. But how and where the brain processes such social-state information is unknown. To home in on the neural substrates of social-state representation, the activity of 196 prefrontal (PFC) neurons was recorded from two monkeys simultaneously during a food-grab task under varying social conditions. Of PFC neurons, 39% showed activity modulation during movement-free periods and seemed to be representing current social state. The direction of modulation was opposite between the dominant and submissive monkeys: During social engagement, PFC activity increased in the dominant monkey and was suppressed in the submissive monkey. The modulation was consistently observed in additional PFC neurons (27/72) in additional pairings with two other monkeys. Notably, PFC activity in one formerly submissive monkey switched to dominant modulation mode when he was paired with a new monkey of lower social status. These findings suggest that PFC, as part of a larger social brain network, maintains a multistate classification of social context for use as a behavioral reference for social decision-making.

  15. Early implicit contextual change detection in anterior prefrontal cortex.

    PubMed

    Pollmann, Stefan; Manginelli, Angela A

    2009-03-31

    The anterior prefrontal cortex is usually associated with high-level executive functions. In contrast, we show anterior prefrontal involvement in implicit change detection processes. A variant of the contextual cueing paradigm was used, in which repeated distractor configurations are implicitly learned and facilitate target search. After only six repetitions, the target location was changed in displays with repeated distractor configurations. We observed selective post-change signal increases in the anterior prefrontal cortex in repeated, but not novel displays. The data support the view that the anterior prefrontal cortex is involved in implicit change detection. This change detection is not dependent on extensive prior learning. Thus, anterior prefrontal involvement in complex cognitive tasks may be due to more basic processes than previously thought.

  16. Prefrontal Cortex and Impulsive Decision Making

    PubMed Central

    Kim, Soyoun; Lee, Daeyeol

    2010-01-01

    Impulsivity refers to a set of heterogeneous behaviors that are tuned suboptimally along certain temporal dimensions. Impulsive inter-temporal choice refers to the tendency to forego a large but delayed reward and to seek an inferior but more immediate reward, whereas impulsive motor responses also result when the subjects fail to suppress inappropriate automatic behaviors. In addition, impulsive actions can be produced when too much emphasis is placed on speed rather than accuracy in a wide range of behaviors, including perceptual decision making. Despite this heterogeneous nature, the prefrontal cortex and its connected areas, such as the basal ganglia, play an important role in gating impulsive actions in a variety of behavioral tasks. Here, we describe key features of computations necessary for optimal decision making, and how their failures can lead to impulsive behaviors. We also review the recent findings from neuroimaging and single-neuron recording studies on the neural mechanisms related to impulsive behaviors. Converging approaches in economics, psychology, and neuroscience provide a unique vista for better understanding the nature of behavioral impairments associated with impulsivity. PMID:20728878

  17. The medial prefrontal cortex exhibits money illusion

    PubMed Central

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

    2009-01-01

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

  18. Optogenetic dissection of medial prefrontal cortex circuitry

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-09-30

    Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted <10 d). Together, these data suggest that intrinsic plasticity within mPFC-BLA projection neurons occurs in a subregion- and cell-type-specific manner during acquisition, consolidation, and extinction of trace fear conditioning. Significance statement: Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel

  20. Lateral prefrontal cortex and self-control in intertemporal choice.

    PubMed

    Figner, Bernd; Knoch, Daria; Johnson, Eric J; Krosch, Amy R; Lisanby, Sarah H; Fehr, Ernst; Weber, Elke U

    2010-05-01

    Disruption of function of left, but not right, lateral prefrontal cortex (LPFC) with low-frequency repetitive transcranial magnetic stimulation (rTMS) increased choices of immediate rewards over larger delayed rewards. rTMS did not change choices involving only delayed rewards or valuation judgments of immediate and delayed rewards, providing causal evidence for a neural lateral-prefrontal cortex-based self-control mechanism in intertemporal choice.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Hochman, Guy; Yechiam, Eldad; Bechara, Antoine

    2011-01-01

    In the past two decades neuroimaging research has substantiated the important role of the prefrontal cortex (PFC) in decision-making. In the current study, we use the complementary lesion based approach to deepen our knowledge concerning the specific cognitive mechanisms modulated by prefrontal activity. Specifically, we assessed the brain substrates implicated in two decision making dimensions in a sample of prefrontal cortex patients: (a) the tendency to differently weigh recent compared to past experience; and (b) the tendency to differently weigh gains compared to losses. The participants performed the Iowa Gambling Task, a complex experience-based decision-making task [3], which was analyzed with a formal cognitive model (the Expectancy-Valance model; [12]). The results indicated that decisions become influenced by more recent, as opposed to older, events when the damage reaches the posterior sectors of the ventromedial prefrontal cortex (VMPC). Furthermore, the degree of this recency deficit was related to the size of the lesion. These results suggest that the posterior area of the prefrontal cortex directly modulates the capacity to use time-delayed information. In contrast, we did not find similar modulation for the sensitivity to gains versus losses. PMID:20412820

  3. Vagus nerve stimulation enhances extinction of conditioned fear and modulates plasticity in the pathway from the ventromedial prefrontal cortex to the amygdala

    PubMed Central

    Peña, David Frausto; Childs, Jessica E.; Willett, Shawn; Vital, Analicia; McIntyre, Christa K.; Kroener, Sven

    2014-01-01

    Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation of new memories that compete with fearful associations. Subjects with posttraumatic stress disorder (PTSD) show impaired extinction of conditioned fear, which is associated with decreased ventromedial prefrontal cortex (vmPFC) control over amygdala activity. Vagus nerve stimulation (VNS) enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here we investigated whether pairing VNS with extinction learning facilitates plasticity between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA). Rats were trained on an auditory fear conditioning task, which was followed by a retention test and 1 day of extinction training. Vagus nerve stimulation or sham-stimulation was administered concurrently with exposure to the fear-conditioned stimulus and retention of fear conditioning was tested again 24 h later. Vagus nerve stimulation-treated rats demonstrated a significant reduction in freezing after a single extinction training session similar to animals that received 5× the number of extinction pairings. To study plasticity in the IL-BLA pathway, we recorded evoked field potentials (EFPs) in the BLA in anesthetized animals 24 h after retention testing. Brief burst stimulation in the IL produced LTD in the BLA field response in fear-conditioned and sham-treated animals. In contrast, the same stimulation resulted in potentiation of the IL-BLA pathway in the VNS-treated group. The present findings suggest that VNS promotes plasticity in the IL-BLA pathway to facilitate extinction of conditioned fear responses (CFRs). PMID:25278857

  4. Modulating activity in the prefrontal cortex changes decision-making for risky gains and losses: a transcranial direct current stimulation study.

    PubMed

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

    2015-06-01

    When making choices under uncertainty, people usually consider both the risks and benefits of each option. Previous studies have found that weighing of risks and benefits during decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but the causal effect of this network on risk decision-making has remained unclear. This experiment was based on a risk-measurement table designed to provide a direct measure of risk preference, with a weighted value of the choices (denoted as weighted risk aversion, WRA) as an index of the participant's degree of risk aversion. We studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex can change the balance of risky vs. safe responses under both gain frame and loss frame. A total of 60 volunteers performed risk tasks while receiving either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. The participants tended to choose more risky options in the gain frame and more safe options in the loss frame after the right anodal/left cathodal tDCS. We also found that right anodal/left cathodal tDCS significantly decreased the WRA values compared with those associated with sham stimulation. These findings extend the notion that DLPFC activity is critical for risk decision-making, indicating an asymmetric role of the right DLPFC in the gain frame vs. the loss frame of risk decision-making. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Neurotensin activates GABAergic interneurons in the prefrontal cortex.

    PubMed

    Petrie, Kimberly A; Schmidt, Dennis; Bubser, Michael; Fadel, Jim; Carraway, Robert E; Deutch, Ariel Y

    2005-02-16

    Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We used in vivo microdialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administration of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]tricyclo(3.3.1.1 [EC] .3.7)decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. We found that D2 agonist-elicited increases in PFC GABA levels were blocked by pretreatment with SR48692, consistent with data indicating that D2 autoreceptor agonists increase neurotensin release from dopamine-neurotensin axons in the PFC. These findings suggest that neurotensin plays an important role in regulating prefrontal cortical interneurons and that it may be useful to consider neurotensin agonists as an adjunct in the treatment of schizophrenia.

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

    PubMed Central

    Politzer-Ahles, Stephen; Gwilliams, Laura

    2015-01-01

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

  7. Prefrontal cortex and neural mechanisms of executive function.

    PubMed

    Funahashi, Shintaro; Andreau, Jorge Mario

    2013-12-01

    Executive function is a product of the coordinated operation of multiple neural systems and an essential prerequisite for a variety of cognitive functions. The prefrontal cortex is known to be a key structure for the performance of executive functions. To accomplish the coordinated operations of multiple neural systems, the prefrontal cortex must monitor the activities in other cortical and subcortical structures and control and supervise their operations by sending command signals, which is called top-down signaling. Although neurophysiological and neuroimaging studies have provided evidence that the prefrontal cortex sends top-down signals to the posterior cortices to control information processing, the neural correlate of these top-down signals is not yet known. Through use of the paired association task, it has been demonstrated that top-down signals are used to retrieve specific information stored in long-term memory. Therefore, we used a paired association task to examine the neural correlates of top-down signals in the prefrontal cortex. The preliminary results indicate that 32% of visual neurons exhibit pair-selectivity, which is similar to the characteristics of pair-coding activities in temporal neurons. The latency of visual responses in prefrontal neurons was longer than bottom-up signals but faster than top-down signals in inferior temporal neurons. These results suggest that pair-selective visual responses may be top-down signals that the prefrontal cortex provides to the temporal cortex, although further studies are needed to elucidate the neural correlates of top-down signals and their characteristics to understand the neural mechanism of executive control by the prefrontal cortex.

  8. Chemistry of the mind: neurochemical modulation of prefrontal cortical function.

    PubMed

    Robbins, Trevor W

    2005-12-05

    The neurochemical modulation of prefrontal cortical function is reviewed with special reference to the ascending dopaminergic and serotoninergic projections. Evidence is surveyed from studies of rats, nonhuman primates, and humans to suggest that prefrontal dopamine has specific functions in attentional control and working memory, mediated mainly through the D1 receptor, whereas manipulations of serotonin are shown by contrast to affect reversal learning in monkeys and human volunteers and measures of impulsivity in rats. These findings are discussed in the context of these as well as other neurotransmitter systems (including noradrenaline and acetylcholine) having distinct roles in the neuromodulation of prefrontal cortical function. The capacity of the prefrontal cortex itself to exert top-down regulation of these ascending neurochemical systems is also discussed. (c) 2005 Wiley-Liss, Inc.

  9. The default modes of reading: modulation of posterior cingulate and medial prefrontal cortex connectivity associated with comprehension and task focus while reading.

    PubMed

    Smallwood, Jonathan; Gorgolewski, Krzysztof J; Golchert, Johannes; Ruby, Florence J M; Engen, Haakon; Baird, Benjamin; Vinski, Melaina T; Schooler, Jonathan W; Margulies, Daniel S

    2013-01-01

    Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN), has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN-the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC)-was predictive of individual differences in reading comprehension and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. Better comprehension was associated with greater functional connectivity with a region of the right insula. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension) and benefits to reading (such as an on-task focus) because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not.

  10. The default modes of reading: modulation of posterior cingulate and medial prefrontal cortex connectivity associated with comprehension and task focus while reading

    PubMed Central

    Smallwood, Jonathan; Gorgolewski, Krzysztof J.; Golchert, Johannes; Ruby, Florence J. M.; Engen, Haakon; Baird, Benjamin; Vinski, Melaina T.; Schooler, Jonathan W.; Margulies, Daniel S.

    2013-01-01

    Reading is a fundamental human capacity and yet it can easily be derailed by the simple act of mind-wandering. A large-scale brain network, referred to as the default mode network (DMN), has been shown to be involved in both mind-wandering and reading, raising the question as to how the same neural system could be implicated in processes with both costs and benefits to narrative comprehension. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to explore whether the intrinsic functional connectivity of the two key midline hubs of the DMN—the posterior cingulate cortex (PCC) and anterior medial prefrontal cortex (aMPFC)—was predictive of individual differences in reading comprehension and task focus recorded outside of the scanner. Worse comprehension was associated with greater functional connectivity between the PCC and a region of the ventral striatum. Better comprehension was associated with greater functional connectivity with a region of the right insula. By contrast reports of increasing task focus were associated with functional connectivity from the aMPFC to clusters in the PCC, the left parietal and temporal cortex, and the cerebellum. Our results suggest that the DMN has both costs (such as poor comprehension) and benefits to reading (such as an on-task focus) because its midline core can couple its activity with other regions to form distinct functional communities that allow seemingly opposing mental states to occur. This flexible coupling allows the DMN to participate in cognitive states that complement the act of reading as well as others that do not. PMID:24282397

  11. Interplay of hippocampus and prefrontal cortex in memory

    PubMed Central

    Preston, Alison R.; Eichenbaum, Howard

    2013-01-01

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

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

    PubMed

    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.

  13. Task alters category representations in prefrontal but not high-level visual cortex.

    PubMed

    Bugatus, Lior; Weiner, Kevin S; Grill-Spector, Kalanit

    2017-04-04

    A central question in neuroscience is how cognitive tasks affect category representations across the human brain. Regions in lateral occipito-temporal cortex (LOTC), ventral temporal cortex (VTC), and ventro-lateral prefrontal cortex (VLFPC) constitute the extended "what" pathway, which is considered instrumental for visual category processing. However, it is unknown (1) whether distributed responses across LOTC, VTC, and VLPC explicitly represent category, task, or some combination of both, and (2) in what way representations across these subdivisions of the extended 'what' pathway may differ. To fill these gaps in knowledge, we scanned 12 participants using fMRI to test the effect of category and task on distributed responses across LOTC, VTC, and VLPFC. Results reveal that task and category modulate responses in both high-level visual regions, as well as prefrontal cortex. However, we found fundamentally different types of representations across the brain. Distributed responses in high-level visual regions are more strongly driven by category than task, and exhibit task-independent category representations. In contrast, distributed responses in prefrontal cortex are more strongly driven by task than category, and contain task-dependent category representations. Together, these findings of differential representations across the brain support a new idea that LOTC and VTC maintain stable and separable category representations allowing efficient processing of visual information, while prefrontal cortex contains flexible representations in which separable category information may emerge only when relevant to the task.

  14. Cerebellar dentate nuclei lesions alter prefrontal cortex dendritic spine morphology.

    PubMed

    Bauer, David J; Peterson, Todd C; Swain, Rodney A

    2014-01-28

    Anatomical tracing studies in primates have revealed neural tracts from the cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in nonmotor processes. Experiments in rats examining the functional role of this cerebellothalamocortical pathway have demonstrated the development of visuospatial and motivational deficits following lesions of the dentate nuclei, in the absence of motor impairment. These behavioral deficits possibly occur due to structural modifications of the cerebral cortex secondary to loss of cerebellar input. The current study characterized morphological alterations in prefrontal cortex important for visuospatial and motivational processes following bilateral cerebellar dentate nuclei lesions. Rats received either bilateral electrolytic cerebellar dentate nuclei lesions or sham surgery followed by a 30-day recovery. Randomly selected Golgi-impregnated neurons in prefrontal cortex were examined for analysis. Measures of branch length and spine density revealed no differences between lesioned and sham rats in either apical or basilar arbors; however, the proportion of immature to mature spines significantly decreased in lesioned rats as compared to sham controls, with reductions of 33% in the basilar arbor and 28% in the apical arbor. Although expected pruning of branches and spines did not occur, the results are consistent with the hypothesis that cerebellar lesions influence prefrontal morphology and support the possibility that functional deficits following cerebellar dentate nuclei lesions are related to prefrontal morphological alteration.

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

    PubMed Central

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

    2011-01-01

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

  16. Functional Segregation of the Human Dorsomedial Prefrontal Cortex

    PubMed Central

    Eickhoff, Simon B.; Laird, Angela R.; Fox, Peter T.; Bzdok, Danilo; Hensel, Lukas

    2016-01-01

    The human dorsomedial prefrontal cortex (dmPFC) has been implicated in various complex cognitive processes, including social cognition. To unravel its functional organization, we assessed the dmPFC's regional heterogeneity, connectivity patterns, and functional profiles. First, the heterogeneity of a dmPFC seed, engaged during social processing, was investigated by assessing local differences in whole-brain coactivation profiles. Second, functional connectivity of the ensuing dmPFC clusters was compared by task-constrained meta-analytic coactivation mapping and task-unconstrained resting-state correlations. Third, dmPFC clusters were functionally profiled by forward/reverse inference. The dmPFC seed was thus segregated into 4 clusters (rostroventral, rostrodorsal, caudal-right, and caudal-left). Both rostral clusters were connected to the amygdala and hippocampus and associated with memory and social cognitive tasks in functional decoding. The rostroventral cluster exhibited strongest connectivity to the default mode network. Unlike the rostral segregation, the caudal dmPFC was divided by hemispheres. The caudal-right cluster was strongly connected to a frontoparietal network (dorsal attention network), whereas the caudal-left cluster was strongly connected to the anterior midcingulate cortex and bilateral anterior insula (salience network). In conclusion, we demonstrate that a dmPFC seed reflecting social processing can be divided into 4 separate functional modules that contribute to distinct facets of advanced human cognition. PMID:25331597

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

    PubMed

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

    2016-07-01

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

  18. The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex.

    PubMed

    Nava, Nicoletta; Treccani, Giulia; Müller, Heidi Kaastrup; Popoli, Maurizio; Wegener, Gregers; Elfving, Betina

    2017-01-01

    It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI). In the present study we evaluated the effects of acute Foot-shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on the gene expression of key regulators of synaptic plasticity and structure. Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI specifically increases the short-term expression of Spinophilin, as well as Homer and Shank family genes, and that both acute stress and DMI exert significant long-term effects on mRNA levels of genes involved in spine plasticity. These findings support the knowledge that acute FS stress and antidepressant treatment induce both rapid and sustained time-dependent alterations in structural components of synaptic plasticity in rodent medial PFC.

  19. Bi-directional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections

    PubMed Central

    Ma, Yao-Ying; Lee, Brian R.; Wang, Xiusong; Guo, Changyong; Liu, Lei; Cui, Ranji; Lan, Yan; Balcita-Pedicino, Judith J.; Wolf, Marina E.; Sesack, Susan R.; Shaham, Yavin; Schlüter, Oliver M.; Huang, Yanhua H.; Dong, Yan

    2014-01-01

    Summary Glutamatergic projections from the medial prefrontal cortex (mPFC) to nucleus accumbens (NAc) contribute to cocaine relapse. Here we show that silent synapse-based remodeling of the two major mPFC-to-NAc projections differentially regulated the progressive increase in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Specifically, cocaine self-administration in rats generated AMPA receptor-silent glutamatergic synapses within both infralimbic (IL) and prelimbic mPFC (PrL) to NAc projections, measured after 1 withdrawal day. After 45 withdrawal days, IL-to-NAc silent synapses became unsilenced/matured by recruiting calcium-permeable (CP) AMPARs, whereas PrL-to-NAc silent synapses matured by recruiting nonCP-AMPARs, resulting in differential remodeling of these projections. Optogenetic reversal of silent synapse-based remodeling of IL-to-NAc and PrL-to-NAc projections potentiated and inhibited, respectively, incubation of cocaine craving on withdrawal day 45. Thus, pro- and anti-relapse circuitry remodeling is induced in parallel after cocaine self-administration. These results may provide novel substrates for utilizing endogenous anti-relapse mechanisms to reduce cocaine relapse. PMID:25199705

  20. Anodal tDCS over the right dorsolateral prefrontal cortex modulates cognitive processing of emotional information as a function of trait rumination in healthy volunteers.

    PubMed

    Vanderhasselt, Marie-Anne; Sanchez, Alvaro; Josephy, Haeike; Baeken, Chris; Brunoni, Andre R; De Raedt, Rudi

    2017-02-01

    Healthy individuals reporting higher (as compared to lower) levels of trait rumination recruit more neural activity in dorso-cortical regions (mostly in the right hemisphere) when inhibiting negative information, possibly to compensate their difficulty to disengage from it. In the present study, we investigated whether these latter neural correlates are causally implicated in cognitive control in these individuals. We administered the Cued Emotional Control Task, a measure of cognitive control indexed by cognitive costs for inhibiting versus providing a habitual response for emotional information, in thirty-five healthy volunteers reporting a broad range of trait rumination levels. Participants completed the task after receiving both real and sham-placebo (counterbalanced order) anodal transcranial Direct Current Stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC). Results reveal that the tDCS induced effects on cognitive costs for emotional information were associated with individual differences in trait rumination: the higher the trait rumination level, the less cognitive costs following real neuromodulation of the right DLPFC. Interestingly, these effects were observed for both positive and negative stimuli, and not only negative information as hypothesized. Overall, the data suggest that the right DLPFC is causally involved in the alteration of cognitive control in healthy individuals who tend to ruminate, possibly by helping them to disengage from emotional material.

  1. Prefrontal connections of the parabelt auditory cortex in macaque monkeys.

    PubMed

    Hackett, T A; Stepniewska, I; Kaas, J H

    1999-01-30

    In the present study, we determined connections of three newly defined regions of auditory cortex with regions of the frontal lobe, and how two of these regions in the frontal lobe interconnect and connect to other portions of frontal cortex and the temporal lobe in macaque monkeys. We conceptualize auditory cortex as including a core of primary areas, a surrounding belt of auditory areas, a lateral parabelt of two divisions, and adjoining regions of temporal cortex with parabelt connections. Injections of several different fluorescent tracers and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were placed in caudal (CPB) and rostral (RPB) divisions of the parabelt, and in cortex of the superior temporal gyrus rostral to the parabelt with parabelt connections (STGr). Injections were also placed in two regions of the frontal lobe that were labeled by a parabelt injection in the same case. The results lead to several major conclusions. First, CPB injections label many neurons in dorsal prearcuate cortex in the region of the frontal eye field and neurons in dorsal prefrontal cortex of the principal sulcus, but few or no neurons in orbitofrontal cortex. Fine-grain label in these same regions as a result of a WGA-HRP injection suggests that the connections are reciprocal. Second, RPB injections label overlapping prearcuate and principal sulcus locations, as well as more rostral cortex of the principal sulcus, and several locations in orbitofrontal cortex. Third, STGr injections label locations in orbitofrontal cortex, some of which overlap those of RPB injections, but not prearcuate or principal sulcus locations. Fourth, injections in prearcuate and principal sulcus locations labeled by a CPB injection labeled neurons in CPB and RPB, with little involvement of the auditory belt and no involvement of the core. In addition, the results indicated that the two frontal lobe regions are densely interconnected. They also connect with largely separate

  2. Capacity-speed relationships in prefrontal cortex.

    PubMed

    Prabhakaran, Vivek; Rypma, Bart; Narayanan, Nandakumar S; Meier, Timothy B; Austin, Benjamin P; Nair, Veena A; Naing, Lin; Thomas, Lisa E; Gabrieli, John D E

    2011-01-01

    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.

  3. Serotonin and Prefrontal Cortex Function: Neurons, Networks, and Circuits

    PubMed Central

    Puig, M. Victoria; Gulledge, Allan T.

    2012-01-01

    Higher-order executive tasks such as learning, working memory, and behavioral flexibility depend on the prefrontal cortex (PFC), the brain region most elaborated in primates. The prominent innervation by serotonin neurons and the dense expression of serotonergic receptors in the PFC suggest that serotonin is a major modulator of its function. The most abundant serotonin receptors in the PFC, 5-HT1A, 5-HT2A and 5-HT3A receptors, are selectively expressed in distinct populations of pyramidal neurons and inhibitory interneurons, and play a critical role in modulating cortical activity and neural oscillations (brain waves). Serotonergic signaling is altered in many psychiatric disorders such as schizophrenia and depression, where parallel changes in receptor expression and brain waves have been observed. Furthermore, many psychiatric drug treatments target serotonergic receptors in the PFC. Thus, understanding the role of serotonergic neurotransmission in PFC function is of major clinical importance. Here we review recent findings concerning the powerful influences of serotonin on single neurons, neural networks, and cortical circuits in the PFC of the rat, where the effects of serotonin have been most thoroughly studied. PMID:22076606

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  6. Left Ventrolateral Prefrontal Cortex and the Cognitive Control of Memory

    ERIC Educational Resources Information Center

    Badre, David; Wagner, Anthony D.

    2007-01-01

    Cognitive control mechanisms permit memory to be accessed strategically, and so aid in bringing knowledge to mind that is relevant to current goals and actions. In this review, we consider the contribution of left ventrolateral prefrontal cortex (VLPFC) to the cognitive control of memory. Reviewed evidence supports a two-process model of mnemonic…

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  8. Stress signalling pathways that impair prefrontal cortex structure and function

    PubMed Central

    2010-01-01

    The prefrontal cortex (PFC)—the most evolved brain region—subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness. PMID:19455173

  9. Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT₁A receptors and stressful experiences.

    PubMed

    Marinho, A L Z; Vila-Verde, C; Fogaça, M V; Guimarães, F S

    2015-06-01

    The infralimbic (IL) and prelimbic (PL) regions of the prefrontal cortex are involved in behavioral responses observed during defensive reactions. Intra-PL or IL injections of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, result in opposite behavioral effects in the contextual fear conditioning (CFC) paradigm. The intra-PL effects of CBD are mediated by 5HT1A receptors and depend on previous stressful experiences but the mechanisms and effects of intra-IL CBD injected are unknown. To this aim the present work verified the effects of intra-IL administration of CBD on two animal models of anxiety, the elevated plus maze (EPM) and CFC. We also investigated if these effects were mediated by 5HT1A receptors and depended on previous stressful experience. Male Wistar rats received bilateral microinjections of vehicle, WAY100635 (5HT1A receptor antagonist, 0.37 nmol) and/or CBD (15, 30 or 60 nmol) before being submitted to the behavioral tests. Intra-IL CBD induced anxiolytic and anxiogenic in the EPM and CFC, respectively. To verify if these effects are influenced by the previous stressful experience (footshocks) in the CFC model, we tested the animals in the EPM 24h after a 2-h restraint period. The anxiolytic-like effect of CBD in the EPM disappeared when the animals were previously stressed. Both responses, i.e., anxiolytic and anxiogenic, were prevented by WAY100635, indicating that they involve local 5HT1A-mediated neurotransmission. Together these results indicate that CBD effects in the IL depend on the nature of the animal model, being influenced by previous stressful experiences and mediated by facilitation of 5HT1A receptors-mediated neurotransmission.

  10. Effects of Neuregulin 3 Genotype on Human Prefrontal Cortex Physiology

    PubMed Central

    Tost, Heike; Callicott, Joseph H.; Rasetti, Roberta; Vakkalanka, Radhakrishna; Mattay, Venkata S.; Weinberger, Daniel R.

    2014-01-01

    The neuregulin 3 gene (NRG3) plays pleiotropic roles in neurodevelopment and is a putative susceptibility locus for schizophrenia. Specifically, the T allele of NRG3 rs10748842 has been associated with illness risk, altered cognitive function, and the expression of a novel splice isoform in prefrontal cortex (PFC), but the neural system effects are unexplored. Here, we report an association between rs10748842 and PFC physiology as measured by functional magnetic resonance imaging of human working memory performance, where a convincing link between increased genetic risk for schizophrenia and increased activation in some PFC areas has been established. In 410 control individuals (195 males, 215 females), we detected a highly significant effect of NRG3 genotype manifesting as an unanticipated increase in ventrolateral PFC activation in nonrisk-associated C allele carriers. An additional analysis including 78 patients with schizophrenia spectrum disorders (64 males, 14 females) and 123 unaffected siblings (53 males, 70 females) revealed a whole-brain significant genotype by group interaction in right dorsolateral PFC (DLPFC), manifesting as a relative activation increase in healthy controls and siblings (C > T/T) and as a hypoactivation in patients (T/T > C). These observed genotype-dependent effects in PFC were not explained by task performance and did not conform to established locales of prefrontal inefficiency linked to genetic risk for schizophrenia. Our data indicate a complex modulation of brain physiology by rs10748842, which does not fit the simple inefficiency model of risk association in DLPFC and suggests that other neurobiological mechanisms are involved. PMID:24431462

  11. Prefrontal cortex and hybrid learning during iterative competitive games

    PubMed Central

    Abe, Hiroshi; Seo, Hyojung; Lee, Daeyeol

    2012-01-01

    Behavioral changes driven by reinforcement and punishment are referred to as simple or model-free reinforcement learning. Animals can also change their behaviors by observing events that are neither appetitive nor aversive, when these events provide new information about payoffs available from alternative actions. This is an example of model-based reinforcement learning, and can be accomplished by incorporating hypothetical reward signals into the value functions for specific actions. Recent neuroimaging and single-neuron recording studies showed that the prefrontal cortex and the striatum are involved not only in reinforcement and punishment, but also in model-based reinforcement learning. We found evidence for both types of learning, and hence hybrid learning, in monkeys during simulated competitive games. In addition, in both the dorsolateral prefrontal cortex and orbitofrontal cortex, individual neurons heterogeneously encoded signals related to actual and hypothetical outcomes from specific actions, suggesting that both areas might contribute to hybrid learning. PMID:22145879

  12. Anterior medial prefrontal cortex implements social priming of mimicry

    PubMed Central

    Hamilton, Antonia F. de C.

    2015-01-01

    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. PMID:25009194

  13. Behavioral control, the medial prefrontal cortex, and resilience

    PubMed Central

    Maier, Steven F.; Amat, Jose; Baratta, Michael V.; Paul, Evan; Watkins, Linda R.

    2006-01-01

    The degree of control that an organism has over a stressor potently modulates the impact of the stressor, with uncontrollable stressors producing a constellation of outcomes that do not occur if the stressor is behaviorally controllable. It has generally been assumed that this occurs because uncontrollability actively potentiates the effects of stressors. Here it will be suggested that in addition, or instead, the presence of control actively inhibits the impact of stressors. At least in part this occurs because (i) the presence of control is detected by regions of the ventral medial prefrontal cortex (mPFCv); and (ii) detection of control activates mPFCv output to stress-responsive brain stem and limbic structures that actively inhibit stress-induced activation of these structures, Furthermore, an initial experience with control over stress alters the mPFCv response to subsequent stressors so that mPFCv output is activated even if the subsequent stressor is uncontrollable, thereby making the organism resilient. The general implications of these results for understanding resilience in the face of adversity are discussed. PMID:17290798

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

    PubMed

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

    2015-11-01

    Social pressure influences human behavior including risk taking, but the psychological and neural underpinnings of this process are not well understood. We used the human lesion method to probe the role of ventromedial prefrontal cortex (vmPFC) in resisting adverse social pressure in the presence of risk. Thirty-seven participants (11 with vmPFC damage, 12 with brain damage outside the vmPFC and 14 without brain damage) were tested in driving simulator scenarios requiring left-turn decisions across oncoming traffic with varying time gaps between the oncoming vehicles. Social pressure was applied by a virtual driver who honked aggressively from behind. Participants with vmPFC damage were more likely to select smaller and potentially unsafe gaps under social pressure, while gap selection by the comparison groups did not change under social pressure. Participants with vmPFC damage also showed prolonged elevated skin conductance responses (SCR) under social pressure. Comparison groups showed similar initial elevated SCR, which then declined prior to making left-turn decisions. The findings suggest that the vmPFC plays an important role in resisting explicit and immediately present social pressure with potentially negative consequences. The vmPFC appears to contribute to the regulation of emotional responses and the modulation of decision making to optimize long-term outcomes. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Susceptibility to social pressure following ventromedial prefrontal cortex damage

    PubMed Central

    Rusch, Michelle L.; Dawson, Jeffrey D.; Rizzo, Matthew; Anderson, Steven W.

    2015-01-01

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

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

    PubMed

    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.

  17. The hierarchical organization of the lateral prefrontal cortex

    PubMed Central

    Nee, Derek Evan; D'Esposito, Mark

    2016-01-01

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

  18. Involvement of the Cannabinoid CB1 Receptor in Modulation of Dopamine Output in the Prefrontal Cortex Associated with Food Restriction in Rats

    PubMed Central

    Biggio, Francesca; Utzeri, Cinzia; Lallai, Valeria; Licheri, Valentina; Lutzu, Stefano; Mostallino, Maria Cristina; Secci, Pietro Paolo; Biggio, Giovanni; Sanna, Enrico

    2014-01-01

    Increase in dopamine output on corticolimbic structures, such as medial prefrontal cortex (mPFC) and nucleus accumbens, has been related to reward effects associated with palatable food or food presentation after a fasting period. The endocannabinoid system regulates feeding behavior through a modulatory action on different neurotransmitter systems, including the dopaminergic system. To elucidate the involvement of type 1 cannabinoid receptors in the regulation of dopamine output in the mPFC associated with feeding in hungry rats, we restricted the food availability to a 2-h period daily for 3 weeks. In food-restricted rats the extracellular dopamine concentration in the mPFC increased starting 80 min before food presentation and returned to baseline after food removal. These changes were attenuated in animals treated with the CB1 receptor antagonist SR141716. To better understand how food restriction can change the response of mesocortical dopaminergic neurons, we studied several components of the neuronal circuit that regulates dopamine output in the mPFC. Patch-clamp experiments revealed that the inhibitory effect of the CB1 receptor agonist WIN 55,212-2 on GABAergic sIPSC frequency was diminished in mPFC neurons of FR compared to fed ad libitum rats. The basal sIPSC frequency resulted reduced in mPFC neurons of food-restricted rats, suggestive of an altered regulation of presynaptic GABA release; these changes were accompanied by an enhanced excitability of mPFC and ventral tegmental area neurons. Finally, type 1 cannabinoid receptor expression in the mPFC was reduced in food-restricted rats. Together, our data support an involvement of the endocannabinoid system in regulation of dopamine release in the mPFC through changes in GABA inhibitory synapses and suggest that the emphasized feeding-associated increase in dopamine output in the mPFC of food-restricted rats might be correlated with an altered expression and function of type 1 cannabinoid receptor in this

  19. A dorsolateral prefrontal cortex semi-automatic segmenter

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

  20. ANTIDEPRESSANT EFFECT OF OPTOGENETIC STIMULATION OF THE MEDIAL PREFRONTAL CORTEX

    PubMed Central

    Covington, Herbert E.; Lobo, Mary Kay; Maze, Ian; Vialou, Vincent; Hyman, James M; Zaman, Samir; LaPlant, Quincey; Mouzon, Ezekiel; Ghose, Subroto; Tamminga, Carol A.; Neve, Rachael L.; Deisseroth, Karl; Nestler, Eric J.

    2010-01-01

    Brain stimulation and imaging studies in humans have highlighted a key role for the prefrontal cortex in clinical depression, however, it remains unknown whether excitation or inhibition of prefrontal cortical neuronal activity is associated with antidepressant responses. Here, we examined cellular indicators of functional activity, including the immediate early genes (IEG), zif268 (egr1), c-fos and arc, in the prefrontal cortex of clinically depressed humans obtained postmortem. We also examined these genes in the ventral portion of the medial prefrontal cortex (mPFC) of mice after chronic social defeat stress, a mouse model of depression. In addition, we used viral vectors to overexpress channel rhodopsin 2 (a light-activated cation channel) in mouse mPFC in order to optogenetically drive “burst” patterns of cortical firing in-vivo and examine the behavioral consequences. Prefrontal cortical tissue derived from clinically depressed humans displayed significant reductions in IEG expression, consistent with a deficit in neuronal activity within this brain region. Mice subjected to chronic social defeat stress exhibited similar reductions in levels of IEG expression in mPFC. Interestingly, some of these changes were not observed in defeated mice that escape the deleterious consequences of the stress, i.e., resilient animals. In those mice that expressed a strong depressive-like phenotype, i.e., susceptible animals, optogenetic stimulation of mPFC exerted potent antidepressant-like effects, without affecting general locomotor activity, anxiety-like behaviors, or social memory. These results indicate that the activity of the mPFC is a key determinant of depression-like behavior, as well as antidepressant responses. PMID:21123555

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

    PubMed

    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.

  2. Prefrontal Cortex and Social Cognition in Mouse and Man

    PubMed Central

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

    2015-01-01

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

  3. Olanzapine Causes a Leptin-Dependent Increase in Acetylcholine Release in Mouse Prefrontal Cortex

    PubMed Central

    Wathen, Asheley B.; West, Emily S.; Lydic, Ralph; Baghdoyan, Helen A.

    2012-01-01

    Study Objectives: The atypical antipsychotic olanzapine is used effectively for treating symptoms of schizophrenia and bipolar disorder. Unwanted effects of olanzapine include slowing of the electroencephalogram (EEG) during wakefulness and increased circulating levels of leptin. The mechanisms underlying the desired and undesired effects of olanzapine are poorly understood. Sleep and wakefulness are modulated by acetylcholine (ACh) in the prefrontal cortex, and leptin alters cholinergic transmission. This study tested the hypothesis that olanzapine interacts with leptin to regulate ACh release in the prefrontal cortex. Design: Within/between subjects. Setting: University of Michigan. Patients or Participants: Adult male C57BL/6J (B6) mice (n = 33) and B6.V-Lepob (leptin-deficient) mice (n = 31). Interventions: Olanzapine was delivered to the prefrontal cortex by microdialysis. Leptin-replacement in leptin-deficient mice was achieved using subcutaneous micro-osmotic pumps. Measurements and Results: Olanzapine caused a concentration-dependent increase in ACh release in B6 and leptin-deficient mice. Olanzapine was 230-fold more potent in leptin-deficient than in B6 mice for increasing ACh release, yet olanzapine caused a 51% greater ACh increase in B6 than in leptin-deficient mice. Olanzapine had no effect on recovery time from general anesthesia. Olanzapine increased EEG power in the delta (0.5-4 Hz) range. Thus, olanzapine dissociated the normal coupling between increased cortical ACh release, increased behavioral arousal, and EEG activation. Leptin replacement significantly enhanced (75%) the olanzapine-induced increase in ACh release. Conclusion: Replacing leptin by systemic administration restored the olanzapine-induced enhancement of ACh release in the prefrontal cortex of leptin-deficient mouse. Citation: Wathen AB; West ES; Lydic R; Baghdoyan HA. Olanzapine causes a leptin-dependent increase in acetylcholine release in mouse prefrontal cortex. SLEEP 2012

  4. Prefrontal cortex lesions disrupt the contextual control of response conflict.

    PubMed

    Haddon, Josephine E; Killcross, Simon

    2006-03-15

    The prefrontal cortex has been implicated in multiple forms of goal-directed behavior. Rats with pretraining lesions to the prefrontal cortex (PFC) or specific lesions to the anterior cingulate cortex (ACC) were trained and tested on a novel behavioral procedure measuring aspects of cue and response competition typical of tests of prefrontal function in humans. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two discriminably different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in both contexts, in extinction. These compounds were formed in such way that the individual elements had dictated either the same (congruent trials) or different (incongruent trials) responses during training. Sham-operated rats used the contextual cues to disambiguate the conflicting response information provided by incongruent stimulus compounds. ACC lesions impaired the contextual control of instrumental responding during incongruent cues during only the initial period of cue presentation, whereas larger PFC lesions abolished incongruent cue performance completely. Neither biconditional discrimination acquisition, nor test performance during congruent stimulus compounds, were affected by the lesions. These findings are consistent with human and nonhuman primate studies, indicating a role for the PFC in the processes by which cues come to control behavior in the face of conflicting information and the ACC specifically in processes such as detection of response conflict. This procedure provides a good foundation for an improved understanding of the disruption to goal-directed behavior seen with frontal dysfunction in a number of neuropsychological disorders including schizophrenia.

  5. Authoritarianism, religious fundamentalism, and the human prefrontal cortex

    PubMed Central

    Asp, Erik; Ramchandran, Kanchna; Tranel, Daniel

    2012-01-01

    Objective The psychological processes of doubting and skepticism have recently become topics of neuroscientific investigation. In this context, we developed the False Tagging Theory, a neurobiological model of the belief and doubt process, which proposes that the prefrontal cortex is critical for normative doubt regarding properly comprehended cognitive representations. Here, we put our theory to an empirical test, hypothesizing that patients with prefrontal cortex damage would have a doubt deficit that would manifest as higher authoritarianism and religious fundamentalism. Method Ten patients with bilateral damage to the ventromedial prefrontal cortex (vmPFC), ten patients with damage to areas outside the vmPFC, and sixteen medical comparison patients, who experienced life-threatening (but non-neurological) medical events, completed a series of scales measuring authoritarianism, religious fundamentalism, and specific religious beliefs. Results VMPFC patients reported significantly higher authoritarianism and religious fundamentalism than the other groups. The degrees of authoritarianism and religious fundamentalism in the vmPFC group were significantly higher than normative values, as well; by contrast, the comparison groups did not differ from normative values. Moreover, vmPFC patients reported increased specific religious beliefs after brain injury. Conclusions The findings support the False Tagging Theory, and suggest that the vmPFC is critical for psychological doubt and resistance to authoritarian persuasion. PMID:22612576

  6. Contribution of Dopamine D1/5 Receptor Modulation of Post-Spike/Burst Afterhyperpolarization to Enhance Neuronal Excitability of Layer V Pyramidal Neurons in Prepubertal Rat Prefrontal Cortex

    PubMed Central

    Yi, Feng; Zhang, Xue-Han; Yang, Charles R.; Li, Bao-ming

    2013-01-01

    Dopamine (DA) receptors in the prefrontal cortex (PFC) modulate both synaptic and intrinsic plasticity that may contribute to cognitive processing. However, the ionic basis underlying DA actions to enhance neuronal plasticity in PFC remains ill-defined. Using whole-cell patch-clamp recordings in layer V-VI pyramidal cells in prepubertal rat PFC, we showed that DA, via activation of D1/5, but not D2/3/4, receptors suppress a Ca2+-dependent, apamin-sensitive K+ channel that mediates post-spike/burst afterhyperpolarization (AHP) to enhance neuronal excitability of PFC neurons. This inhibition is not dependent on HCN channels. The D1/5 receptor activation also enhanced an afterdepolarizing potential (ADP) that follows the AHP. Additional single-spike analyses revealed that DA or D1/5 receptor activation suppressed the apamin-sensitive post-spike mAHP, further contributing to the increase in evoked spike firing to enhance the neuronal excitability. Taken together, the D1/5 receptor modulates intrinsic mechanisms that amplify a long depolarizing input to sustain spike firing outputs in pyramidal PFC neurons. PMID:23977170

  7. More is less: a disinhibited prefrontal cortex impairs cognitive flexibility.

    PubMed

    Gruber, Aaron J; Calhoon, Gwendolyn G; Shusterman, Igor; Schoenbaum, Geoffrey; Roesch, Matthew R; O'Donnell, Patricio

    2010-12-15

    The prefrontal cortex (PFC) is critical for decision making, and it becomes dysfunctional in many neuropsychiatric disorders. Studies in schizophrenia patients and relevant animal models suggest loss of PFC inhibitory interneuron function. For instance, rats with a neonatal ventral hippocampal lesion (NVHL) show a deficient modulation of PFC interneurons by dopamine (DA). Whether the PFC becomes disinhibited in this model and alters decision making remains to be determined. Here, we recorded neural activity in the medial PFC of NVHL rats during a reward-discounting choice task that activated DA systems. Rats were trained to sample odors that instructed them to select one of two feeders that delivered unequal amounts of liquid. Putative pyramidal neurons in the PFC were hyperactive whereas task-related field potential oscillations were significantly reduced in NVHL rats, consistent with impaired interneuron activation by DA during odor sampling leading to disorganized processing. Cognitive flexibility was tested by examining response bias and errors after reversing reward outcomes. NVHL rats demonstrated impaired flexibility as they were less able to track changes in reward outcome and made more response errors than controls did. Reducing cortical excitability with the metabotropic glutamate receptor 2/3 agonist LY379268 (1 mg/kg, i.p.) improved behavioral flexibility in NVHL rats but not controls. Furthermore, D2 dopamine receptors were involved, as the antagonist eticlopride (0.02 mg/kg, i.p.) reduced the ability to switch only in control animals. We conclude that NVHL rats present PFC disinhibition, which affects neural information processing and the selection of appropriate behavioral responses.

  8. More is less: a disinhibited prefrontal cortex impairs cognitive flexibility

    PubMed Central

    Gruber, A.J.; Calhoon, G.G.; Shusterman, I.; Schoenbaum, G.; Roesch, M.R.; O’Donnell, P.

    2010-01-01

    The prefrontal cortex (PFC) is critical for decision making, and it becomes dysfunctional in many neuropsychiatric disorders. Studies in schizophrenia patients and relevant animal models suggest loss of PFC inhibitory interneuron function. For instance, rats with a neonatal ventral hippocampal lesion (NVHL) show a deficient modulation of PFC interneurons by dopamine (DA). Whether the PFC becomes disinhibited in this model and alters decision-making remains to be determined. Here, we recorded neural activity in the medial PFC of NVHL rats during a reward-discounting choice task that activates DA systems. Rats were trained to sample odors that instructed them to select one of two feeders that delivered unequal amounts of liquid. Putative pyramidal neurons in the PFC were hyperactive while task-related field potential oscillations were significantly reduced in NVHL rats, consistent with impaired interneuron activation by DA during odor sampling leading to disorganized processing. Cognitive flexibility was tested by examining response bias and errors after reversing reward outcomes. NVHL rats demonstrated impaired flexibility as they were less able to track changes in reward outcome and made more response errors than controls. Reducing cortical excitability with the metabotropic glutamate receptor 2/3 agonist LY379268 (1 mg/kg, i.p.) improved behavioral flexibility in NVHL rats but not controls. Furthermore, D2 dopamine receptors were involved, as the antagonist eticlopride (0.02 mg/kg, i.p.) reduced the ability to switch in only control animals. We conclude that NVHL rats present PFC disinhibition, which affects neural information processing and the selection of appropriate behavioral responses. PMID:21159980

  9. Gentle touch activates the anterior prefrontal cortex: an NIRS study.

    PubMed

    Kida, Tetsuo; Shinohara, Kazuyuki

    2013-01-01

    Gentle touching of the hand activates emotion- and reward-related regions of the brain. The present study investigated activation of the prefrontal cortex by gentle sweeps of the palm or forearm with three materials (wood, velvet, paintbrush) using near-infrared spectroscopy (NIRS). Sweeps of the left palm with a sensuous velvet fabric increased the oxy-hemoglobin (oxy-Hb) concentration in the frontal-polar cortex (FPC) and a part of the orbitofrontal cortex (OFC), compared to a neutral touch produced by rounded wood. Pleasantness ratings were higher for the velvet than wood. In conclusion, the present study revealed the involvement of the FPC/OFC in pleasant emotion produced by gentle touch to the hand. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  10. Dorsolateral and ventromedial prefrontal cortex orchestrate normative choice.

    PubMed

    Baumgartner, Thomas; Knoch, Daria; Hotz, Philine; Eisenegger, Christoph; Fehr, Ernst

    2011-10-02

    Humans are noted for their capacity to over-ride self-interest in favor of normatively valued goals. We examined the neural circuitry that is causally involved in normative, fairness-related decisions by generating a temporarily diminished capacity for costly normative behavior, a 'deviant' case, through non-invasive brain stimulation (repetitive transcranial magnetic stimulation) and compared normal subjects' functional magnetic resonance imaging signals with those of the deviant subjects. When fairness and economic self-interest were in conflict, normal subjects (who make costly normative decisions at a much higher frequency) displayed significantly higher activity in, and connectivity between, the right dorsolateral prefrontal cortex (DLPFC) and the posterior ventromedial prefrontal cortex (pVMPFC). In contrast, when there was no conflict between fairness and economic self-interest, both types of subjects displayed identical neural patterns and behaved identically. These findings suggest that a parsimonious prefrontal network, the activation of right DLPFC and pVMPFC, and the connectivity between them, facilitates subjects' willingness to incur the cost of normative decisions.

  11. Virtual Reality and the Role of the Prefrontal Cortex in Adults and Children

    PubMed Central

    Jäncke, Lutz; Cheetham, Marcus; Baumgartner, Thomas

    2009-01-01

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

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

    PubMed

    Jäncke, Lutz; Cheetham, Marcus; Baumgartner, Thomas

    2009-05-01

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

  13. Characterization of spontaneous, transient adenosine release in the caudate-putamen and prefrontal cortex.

    PubMed

    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 (N(6)-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.

  14. Value, pleasure and choice in the ventral prefrontal cortex.

    PubMed

    Grabenhorst, Fabian; Rolls, Edmund T

    2011-02-01

    Rapid advances have recently been made in understanding how value-based decision-making processes are implemented in the brain. We integrate neuroeconomic and computational approaches with evidence on the neural correlates of value and experienced pleasure to describe how systems for valuation and decision-making are organized in the prefrontal cortex of humans and other primates. We show that the orbitofrontal and ventromedial prefrontal (VMPFC) cortices compute expected value, reward outcome and experienced pleasure for different stimuli on a common value scale. Attractor networks in VMPFC area 10 then implement categorical decision processes that transform value signals into a choice between the values, thereby guiding action. This synthesis of findings across fields provides a unifying perspective for the study of decision-making processes in the brain.

  15. Prefrontal Cortex in Learning to Overcome Generalized Fear

    PubMed Central

    Korzus, Edward

    2015-01-01

    SUMMARY 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 discrimination learning are discussed. These studies suggest that prefrontal N-methyl-D-aspartate receptors expressed in excitatory neurons govern fear discrimination learning via a mechanism involving cAMP response element-binding protein–dependent engagement of acetyltransferase. PMID:26244030

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

    PubMed

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

    2015-10-01

    Neuroimaging and behavioral evidence has suggested that the lateral prefrontal cortex is involved in individual differences in working memory capacity (WMC). However, few studies have localized the neural structures that differentiate high and low WMC individuals, considering the functional architecture of the prefrontal cortex. The present study aimed to identify a frontal region that underlies individual differences from the perspective of the hierarchical architecture of the frontal cortex. By manipulating an episodic factor of cognitive control (control in selecting an appropriate task set according to a temporal context) and using a parametric modulation analysis, we found that both high- and low- WMC individuals have similar activation patterns in the premotor cortex (BA6, 8), caudal prefrontal cortex (BA44, 45), and frontopolar cortex (BA10, 11), but differed in the rostral part of the prefrontal cortex (BA46/47); high WMC individuals showed greater activation in the higher episodic control condition, whereas low WMC individuals showed reduced activation when episodic control was required. Similar patterns of activation were found in the right inferior parietal and middle/inferior temporal cortices. These results indicate that the rostral prefrontal cortex, which supports episodic cognitive control, possibly by sending a weighting signal toward the inferior parietal and middle/inferior temporal cortices that modulate saliency and sensory processing, underlies individual differences in WMC. Episodic control account, which considers the organization of the prefrontal cortex, fits well with previous findings of individual differences in WMC. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    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. PMID:24550789

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

    PubMed

    Kostopoulos, Penelope; Petrides, Michael

    2016-02-16

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

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

    PubMed Central

    Kostopoulos, Penelope; Petrides, Michael

    2016-01-01

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

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

    PubMed

    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.

  1. A Study on a Brain-Computer Interface for Motor Assist by Prefrontal Cortex

    NASA Astrophysics Data System (ADS)

    Misawa, Tadanobu; Takano, Shinya; Shimokawa, Tetsuya; Hirobayashi, Shigeki

    In recent times, considerable research has been conducted on the development of brain-computer interfaces (BCIs). Although there have been several reports on BCIs that assist motor functions by measurement of brain activity in the motor cortex, only a few studies have reported on BCI that assist motor functions by measurement of activity in areas other than the motor cortex. In this study, we experimentally develop a BCI that assists motor functions on the basis of brain activity in the prefrontal cortex. In this BCI system, subjects are shown the labyrinth problem. Concretely, brain activity is measured using fNIRS and the data are acquired in real time. The signal processing module implements low pass filtering of these signals. Further, the pattern classification module used in this system currently is a support vector machine. 22 subjects, both male and female, volunteered to participate in this experiment. 8 of these 22 subjects were able to solve the labyrinth problem. In this experiment, we could not obtain a high distinction. However, these results show that it is possible to develop BCI systems that assist motor functions using information from the prefrontal cortex.

  2. The prefrontal cortex achieves inhibitory control by facilitating subcortical motor pathway connectivity.

    PubMed

    Rae, Charlotte L; Hughes, Laura E; Anderson, Michael C; Rowe, James B

    2015-01-14

    Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control.

  3. The Prefrontal Cortex Achieves Inhibitory Control by Facilitating Subcortical Motor Pathway Connectivity

    PubMed Central

    Hughes, Laura E.; Anderson, Michael C.; Rowe, James B.

    2015-01-01

    Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control. PMID:25589771

  4. Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

    PubMed Central

    Roenker, Nicole L.; Gudelsky, Gary A.; Ahlbrand, Rebecca; Horn, Paul S.; Richtand, Neil M.

    2012-01-01

    Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release. PMID:22579658

  5. The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.

    PubMed

    Shalini, Suku-Maran; Herr, Deron R; Ong, Wei-Yi

    2016-10-01

    Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.

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

    PubMed

    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.

  7. The effects of thioperamide on extracellular levels of glutamate and GABA in the rat prefrontal cortex.

    PubMed

    Welty, Natalie; Shoblock, James R

    2009-12-01

    Histamine H3 receptors (H3R) are presynaptic heteroreceptors that negatively modulate the release of histamine and other neurotransmitters such as acetylcholine. Blocking H3 receptors with antagonists/inverse agonists has been shown to be procognitive and this effect has often been associated with increases in acetylcholine transmission. H3 receptors are abundantly expressed in the prefrontal cortex, an area associated with cognitive performance. While the procognitive effects of H3 receptor antagonists/inverse agonists may depend on alterations to acetylcholine or histamine release, other transmitters involved in cognitive processing such as glutamate and gamma-aminobutyric acid (GABA) may also be involved. The purpose of the present study was to examine the effects of thioperamide, an H3 receptor antagonist, on extracellular levels of glutamate and GABA in the prefrontal cortex. By means of in vivo microdialysis on freely moving Sprague Dawley rats, samples were collected and assayed via high-performance liquid chromatography coupled to electrochemical detection. Replacement of calcium with magnesium revealed that the release of GABA, but not glutamate, was calcium-dependent. Thioperamide (10-20 mg/kg) did not affect basal glutamate or GABA release. Perfusion with a high concentration of potassium (100 mM) increased GABA, but not glutamate, release and thioperamide (20 mg/kg) attenuated the effects of high potassium on GABA release. These data indicate that H3 receptors in the prefrontal cortex can enhance stimulated GABA release, but do not regulate basal levels of glutamate or GABA.

  8. Neural Coding of Tactile Decisions in the Human Prefrontal Cortex

    PubMed Central

    Pleger, Burkhard; Ruff, Christian C.; Blankenburg, Felix; Bestmann, Sven; Wiech, Katja; Stephan, Klaas E.; Capilla, Almudena; Friston, Karl J.; Dolan, Raymond J.

    2009-01-01

    The neural processes underlying tactile decisions in the human brain remain elusive. We addressed this question in a functional magnetic resonance imaging study using a somatosensory discrimination task, requiring participants to compare the frequency of two successive tactile stimuli. Tactile stimuli per se engaged somatosensory, parietal, and frontal cortical regions. Using a statistical model that accounted for the relative difference in frequencies (i.e., Weber fraction) and discrimination accuracy (i.e., correct or incorrect), we show that trial-by-trial relative frequency difference is represented linearly by activity changes in the left dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex, and bilateral anterior insular cortices. However, a circumscribed region within the left DLPFC showed a different response pattern expressed as activity changes that were monotonically related to relative stimulation difference only for correct but not for incorrect trials. Our findings suggest that activity in the left DLPFC encodes stimulus representations that underlie veridical tactile decisions in humans. PMID:17135421

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

    PubMed Central

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

    2015-01-01

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

  10. Cholinergic synaptic circuitry in the macaque prefrontal cortex.

    PubMed

    Mrzljak, L; Pappy, M; Leranth, C; Goldman-Rakic, P S

    1995-07-10

    Surprisingly little is known about the synaptic architecture of the cholinergic innervation in the primate cerebral cortex in spite of its acknowledged relevance to cognitive processing and Alzheimer's disease. To address this knowledge gap, we examined serially sectioned cholinergic axons in supra- and infragranular layers of the macaque prefrontal cortex by using an antibody against the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The tissue bound antibody was visualized with both immunoperoxidase and silver-enhanced diaminobenzidine sulfide (SEDS) techniques. Both methods revealed that cholinergic axons make synapses in all cortical layers and that these synapses are exclusively symmetric. Cholinergic axons formed synapses primarily on dendritic shafts (70.5%), dendritic spines (25%), and, to a lesser extent, cell bodies (4.5%). Both pyramidal neurons and cells exhibiting the morphological features of GABAergic cells were targets of the cholinergic innervation. Some spiny dendritic shafts received multiple, closely spaced synapses, suggesting that a subset of pyramidal neurons may be subject to a particularly strong cholinergic influence. Analysis of synaptic incidence of cholinergic profiles in the supragranular layers of the prefrontal cortex by the SEDS technique revealed that definitive synaptic junctions were formed by 44% of the cholinergic boutons. An unexpected finding was that cholinergic boutons were frequently apposed to spines and small dendrites without making any visible synaptic specializations. These same spines and dendrites often received asymmetric synapses, presumably of thalamocortical or corticocortical origin. Present ultrastructural findings suggest that acetylcholine may have a dual modulatory effect in the neocortex: one through classical synaptic junctions on dendritic shafts and spines, and the other through nonsynaptic appositions in close vicinity to asymmetric synapses. Further physiological studies are

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

    PubMed Central

    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

  12. Action observation activates neurons of the monkey ventrolateral prefrontal cortex

    PubMed Central

    Simone, Luciano; Bimbi, Marco; Rodà, Francesca; Fogassi, Leonardo; Rozzi, Stefano

    2017-01-01

    Prefrontal cortex is crucial for exploiting contextual information for the planning and guidance of behavioral responses. Among contextual cues, those provided by others’ behavior are particularly important, in primates, for selecting appropriate reactions and suppressing the inappropriate ones. These latter functions deeply rely on the ability to understand others’ actions. However, it is largely unknown whether prefrontal neurons are activated by action observation. To address this issue, we recorded the activity of ventrolateral prefrontal (VLPF) neurons of macaque monkeys during the observation of videos depicting biological movements performed by a monkey or a human agent, and object motion. Our results show that a population of VLPF neurons respond to the observation of biological movements, in particular those representing goal directed actions. Many of these neurons also show a preference for the agent performing the action. The neural response is present also when part of the observed movement is obscured, suggesting that these VLPF neurons code a high order representation of the observed action rather than a simple visual description of it. PMID:28290511

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

    PubMed

    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.

  14. Autonomic and prefrontal cortex responses to autobiographical recall of emotions.

    PubMed

    Marci, Carl D; Glick, Debra M; Loh, Rebecca; Dougherty, Darin D

    2007-09-01

    The present study combined measures of regional cerebral blood flow (rCBF) using positron emission tomography (PET) with measures of the autonomic nervous system using skin conductance (SC), heart rate (HR), and the high frequency band of heart rate variability (HRV) in ten healthy participants who were exposed to autobiographical scripts of memories for three target emotions: anger, happiness, and sadness. According to the results, anger was the only emotion to show a significant increase in sympathetic activity, accompanied by a significant decrease in HRV when compared with a neutral script. Anger was also the only emotion to show significant changes in rCBF in the prefrontal cortex. By contrast, the results for the happy and sad conditions showed no significant increase in sympathetic activity and no changes in rCBF in the prefrontal cortex in comparison with the neutral script. The findings suggest that a relative increase in sympathetic activity with a reciprocal decrease in parasympathetic activity may be necessary to generate frontal activity in autobiographical recall of emotions.

  15. Prefrontal Cortex and Neurological Impairments of Active Thought.

    PubMed

    Shallice, Tim; Cipolotti, Lisa

    2017-08-16

    This article reviews the effects of lesions to the frontal cortex on the ability to carry out active thought, namely, to reason, think flexibly, produce strategies, and formulate and realize plans.Wediscuss how and why relevant neuropsychological studies should be carried out. The relationships between active thought and both intelligence and language are considered. The following basic processes necessary for effective active thought are reviewed: concentration, set switching, inhibiting potentiated responses, and monitoring and checking. Different forms of active thought are then addressed: abstraction, deduction, reasoning in well-structured and ill-structured problem spaces, novel strategy generation, and planning. We conclude that neuropsychological findings are valuable for providing information on systems rather than networks, especially information concerning prefrontal lateralization of function. We present a synthesis of the respective roles of the left and right lateral prefrontal cortex in active thought. Expected final online publication date for the Annual Review of Psychology Volume 69 is January 4, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  16. Faces and Eyes in Human Lateral Prefrontal Cortex

    PubMed Central

    Chan, Annie W.-Y.; Downing, Paul E.

    2011-01-01

    Much of the work on face-selective neural activity has focused on posterior, ventral areas of the human and non-human primate brain. However, electrophysiological and fMRI studies have identified face responses in the prefrontal cortex. Here we used fMRI to characterize these responses in the human prefrontal cortex compared with face selectivity in posterior ventral region. We examined a region at the junction of the right inferior frontal sulcus and the precentral sulcus (right inferior frontal junction or rIFJ) that responds more to faces than to several other object categories. We find that the rIFJ and the right fusiform face area (rFFA) are broadly similar in their responses to whole faces, headless bodies, tools, and scenes. Strikingly, however, while the rFFA preferentially responds to the whole face, the rIFJ response to faces appears to be driven primarily by the eyes. This dissociation provides clues to the functional role of the rIFJ face response. We speculate on this role with reference to emotion perception, gaze perception, and to behavioral relevance more generally. PMID:21687796

  17. Dopamine, Salience, and Response Set Shifting in Prefrontal Cortex.

    PubMed

    Shiner, T; Symmonds, M; Guitart-Masip, M; Fleming, S M; Friston, K J; Dolan, R J

    2015-10-01

    Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. L-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease.

  18. Dopamine, Salience, and Response Set Shifting in Prefrontal Cortex

    PubMed Central

    Shiner, T.; Symmonds, M.; Guitart-Masip, M.; Fleming, S. M.; Friston, K. J.; Dolan, R. J.

    2015-01-01

    Dopamine is implicated in multiple functions, including motor execution, action learning for hedonically salient outcomes, maintenance, and switching of behavioral response set. Here, we used a novel within-subject psychopharmacological and combined functional neuroimaging paradigm, investigating the interaction between hedonic salience, dopamine, and response set shifting, distinct from effects on action learning or motor execution. We asked whether behavioral performance in response set shifting depends on the hedonic salience of reversal cues, by presenting these as null (neutral) or salient (monetary loss) outcomes. We observed marked effects of reversal cue salience on set-switching, with more efficient reversals following salient loss outcomes. l-Dopa degraded this discrimination, leading to inappropriate perseveration. Generic activation in thalamus, insula, and striatum preceded response set switches, with an opposite pattern in ventromedial prefrontal cortex (vmPFC). However, the behavioral effect of hedonic salience was reflected in differential vmPFC deactivation following salient relative to null reversal cues. l-Dopa reversed this pattern in vmPFC, suggesting that its behavioral effects are due to disruption of the stability and switching of firing patterns in prefrontal cortex. Our findings provide a potential neurobiological explanation for paradoxical phenomena, including maintenance of behavioral set despite negative outcomes, seen in impulse control disorders in Parkinson's disease. PMID:25246512

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

    PubMed

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

    2015-10-01

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

  20. Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala

    PubMed Central

    Harada, Tokiko; Sadato, Norihiro

    2011-01-01

    Neural correlates involved in the formation of negative impression from face were investigated using event-related functional magnetic resonance imaging and a partial conditioning paradigm. Eighteen normal volunteers underwent imaging while they viewed the faces of two unfamiliar individuals: one individual’s face was partially accompanied by negative emotion but the other’s was not. After the volunteers learned the relationship between the faces and the emotion, they formed a more negative impression of the person’s face when the emotion was presented. Subtraction analysis of the individuals’ neutral faces revealed activation in the dorsal anterior cingulate cortex and superior temporal sulcus, but this activity did not correlate with the change of impression from face. On the other hand, the response in the left amygdala negatively correlated with the change of impression from face in the first run. Time modulation analysis revealed that activity in the dorsomedial prefrontal cortex associated with negative emotion was the largest in the initial part of the acquisition. These results suggest that a negative impression from face may be formed by orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior cingulate cortex and amygdala, and that the activity has a prominent role in the initial acquisition of negative emotion. PMID:20693390

  1. Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala.

    PubMed

    Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

    2011-09-01

    Neural correlates involved in the formation of negative impression from face were investigated using event-related functional magnetic resonance imaging and a partial conditioning paradigm. Eighteen normal volunteers underwent imaging while they viewed the faces of two unfamiliar individuals: one individual's face was partially accompanied by negative emotion but the other's was not. After the volunteers learned the relationship between the faces and the emotion, they formed a more negative impression of the person's face when the emotion was presented. Subtraction analysis of the individuals' neutral faces revealed activation in the dorsal anterior cingulate cortex and superior temporal sulcus, but this activity did not correlate with the change of impression from face. On the other hand, the response in the left amygdala negatively correlated with the change of impression from face in the first run. Time modulation analysis revealed that activity in the dorsomedial prefrontal cortex associated with negative emotion was the largest in the initial part of the acquisition. These results suggest that a negative impression from face may be formed by orchestrated activity in the dorsomedial prefrontal cortex, dorsal anterior cingulate cortex and amygdala, and that the activity has a prominent role in the initial acquisition of negative emotion.

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  4. Distributed value representation in the medial prefrontal cortex during intertemporal choices.

    PubMed

    Wang, Qiang; Luo, Shan; Monterosso, John; Zhang, Jintao; Fang, Xiaoyi; Dong, Qi; Xue, Gui

    2014-05-28

    The ability to resist current temptations in favor of long-term benefits is a critical human capacity. Despite the extensive studies on the neural mechanisms of intertemporal choices, how the subjective value of immediate and delayed rewards is represented and compared in the brain remains to be elucidated. The present fMRI study addressed this question by simultaneously and independently manipulating the magnitude of immediate and delayed rewards in an intertemporal decision task, combined with univariate analysis and multiple voxel pattern analysis. We found that activities in the posterior portion of the dorsal medial prefrontal cortex (DmPFC) were modulated by the value of immediate options, whereas activities in the adjacent anterior DmPFC were modulated by the subjective value of delayed options. Brain signal change in the ventral mPFC was positively correlated with the "relative value" (the absolute difference of subjective value between two intertemporal alternatives). In contrast, the dorsal anterior cingulate cortex activity was negatively correlated with the relative value. These results suggest that immediate and delayed rewards are separately represented in the dorsal mPFC and compared in the ventral mPFC to guide decisions. The functional dissociation of posterior and anterior DmPFC in representing immediate and delayed reward is consistent with the general structural and functional architecture of the prefrontal cortex and may provide a neural basis for human's unique capacity to delayed gratification. Copyright © 2014 the authors 0270-6474/14/347522-09$15.00/0.

  5. Neural structures underlying set-shifting: roles of medial prefrontal cortex and anterior cingulate cortex.

    PubMed

    Bissonette, Gregory B; Powell, Elizabeth M; Roesch, Matthew R

    2013-08-01

    Impaired attentional set-shifting and inflexible decision-making are problems frequently observed during normal aging and in several psychiatric disorders. To understand the neuropathophysiology of underlying inflexible behavior, animal models of attentional set-shifting have been developed to mimic tasks such as the Wisconsin Card Sorting Task (WCST), which tap into a number of cognitive functions including stimulus-response encoding, working memory, attention, error detection, and conflict resolution. Here, we review many of these tasks in several different species and speculate on how prefrontal cortex and anterior cingulate cortex might contribute to normal performance during set-shifting. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Capturing the temporal evolution of choice across prefrontal cortex

    PubMed Central

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

    2015-01-01

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

  7. Extinction circuits for fear and addiction overlap in prefrontal cortex

    PubMed Central

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

    2009-01-01

    Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is critical for the extinction of both fear and drug-seeking behaviors. Moreover, a dorsal-ventral distinction is apparent within the mPFC, such that the prelimbic (PL-mPFC) cortex drives the expression of fear and drug seeking, whereas the infralimbic (IL-mPFC) cortex suppresses these behaviors after extinction. For conditioned fear, the dorsal-ventral dichotomy is accomplished via divergent projections to different subregions of the amygdala, whereas for drug seeking, it is accomplished via divergent projections to the subregions of the nucleus accumbens. Given that the mPFC represents a common node in the extinction circuit for these behaviors, treatments that target this region may help alleviate symptoms of both anxiety and addictive disorders by enhancing extinction memory. PMID:19380710

  8. Affective ambiguity for a group recruits ventromedial prefrontal cortex.

    PubMed

    Simmons, Alan; Stein, Murray B; Matthews, Scott C; Feinstein, Justin S; Paulus, Martin P

    2006-01-15

    Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.

  9. NIRS-based neurofeedback learning systems for controlling activity of the prefrontal cortex.

    PubMed

    Sakatani, Kaoru; Takemoto, N; Tsujii, T; Yanagisawa, K; Tsunashima, H

    2013-01-01

    The aim of this study was to develop a NIRS-based neurofeedback system to modulate activity in the prefrontal cortex (PFC). We evaluated the effectiveness of the system in terms of separability of changes in oxy-Hb and its derivative. Training with neurofeedback resulted in higher separability than training without neurofeedback or no training, suggesting that the neurofeedback system could enhance self-control of PFC activity. Interestingly, the dorsolateral PFC exhibited enhanced activity and high separability after neurofeedback training. These observations suggest that the neurofeedback system might be useful for training subjects to regulate emotions by self-control of dorsolateral PFC activity.

  10. The vigilance promoting drug modafinil modulates serotonin transmission in the rat prefrontal cortex and dorsal raphe nucleus. Possible relevance for its postulated antidepressant activity.

    PubMed

    Ferraro, Luca; Antonelli, Tiziana; Beggiato, Sarah; Cristina Tomasini, Maria; Fuxe, Kjell; Tanganelli, Sergio

    2013-04-01

    Modafinil, (RS)-2-(diphenylmethylsulfinyl)acetamide derivative (Modiodal, Provigil), is a vigilance-promoting agent which reduces sleep episodes by improving wakefulness. It is approved by the USA FDA for narcolepsy, shiftwork sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure. Unlike classical psychostimulants such as amphetamine and amphetamine-like compounds, the awaking effect of modafinil is not associated with a disturbance of nighttime sleep, tolerance, and sensitization. Its precise mechanism of action is still unclear. In animal studies, modafinil and its analogues have been shown to modify dopaminergic, noradrenergic, glutamatergic, GABAergic, serotoninergic, orexinergic, and histaminergic pathways. Besides the approved use in sleep disorders, modafinil has been investigated for the treatment of fatigue, impaired cognition and some symptoms in a number of other disorders. In particular, clinical studies seem to indicate that the drug could be particularly successful in the treatment of depression and its use in major depressive and bipolar disorders, has been suggested. However, the molecular mechanisms underlying this possible effect are still unknown. The present review firstly summarizes the structure-activity relationship studies and the mechanism of action of modafinil and its related compounds. Then, it focuses on data demonstrating that modafinil interacts with serotonin neuronal activity in rat frontal cortex and dorsal raphe nucleus, two brain areas linked together and involved in depression. Preclinical and clinical evidence of a positive interaction between modafinil and classical antidepressant drugs, is also summarized.

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

    PubMed Central

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

    2011-01-01

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

  12. Human cognition. Foundations of human reasoning in the prefrontal cortex.

    PubMed

    Donoso, Maël; Collins, Anne G E; Koechlin, Etienne

    2014-06-27

    The prefrontal cortex (PFC) subserves reasoning in the service of adaptive behavior. Little is known, however, about the architecture of reasoning processes in the PFC. Using computational modeling and neuroimaging, we show here that the human PFC has two concurrent inferential tracks: (i) one from ventromedial to dorsomedial PFC regions that makes probabilistic inferences about the reliability of the ongoing behavioral strategy and arbitrates between adjusting this strategy versus exploring new ones from long-term memory, and (ii) another from polar to lateral PFC regions that makes probabilistic inferences about the reliability of two or three alternative strategies and arbitrates between exploring new strategies versus exploiting these alternative ones. The two tracks interact and, along with the striatum, realize hypothesis testing for accepting versus rejecting newly created strategies.

  13. Intact discourse cohesion and coherence following bilateral ventromedial prefrontal cortex.

    PubMed

    Kurczek, Jake; Duff, Melissa C

    2012-12-01

    Discourse cohesion and coherence give communication its continuity providing the grammatical and lexical links that hold an utterance or text together and give it meaning. Researchers often link cohesion and coherence deficits to the frontal lobes by drawing attention to frontal lobe dysfunction in populations where discourse cohesion and coherence deficits are reported and through attribution of these deficits to underlying cognitive impairments putatively associated with the frontal lobes. We examined the distinct contribution of a region of the frontal lobes, the ventromedial prefrontal cortex (vmPFC), to discourse cohesion and coherence across a range of discourse tasks. We found that bilateral vmPFC damage does not impair cohesion and coherence in spoken discourse. This study provides insights into the contribution of the major anatomical subdivisions of the frontal lobes to language use and furthers our understanding of the neural and cognitive underpinnings of discourse cohesion and coherence.

  14. Behavioral effects of congenital ventromedial prefrontal cortex malformation

    PubMed Central

    2011-01-01

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

  15. Medial prefrontal cortex predicts internally driven strategy shifts

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  17. Prefrontal cortex is involved in internal decision of forthcoming saccades.

    PubMed

    Milea, Dan; Lobel, Elie; Lehéricy, Stéphane; Leboucher, Pierre; Pochon, Jean-Baptiste; Pierrot-Deseilligny, Charles; Berthoz, Alain

    2007-08-06

    Deciding where to look is mandatory to explore the visual world. To study the neural correlates subserving the cognitive phase of self-initiated eye movements in humans, we tested 12 healthy participants, using event-related functional MRI. Changes in the frontal-cortical activity preceding voluntary saccades were studied when the participants freely decided the direction of a forthcoming saccade, compared with a condition in which they had only to prepare an externally cued saccade. Self-initiation of saccades, before their execution, was specifically associated with frontal-lobe activation in the dorsolateral prefrontal cortex, and in the right presupplementary eye field and frontal eye fields, suggesting the roles of these areas in the decision process of where to look when facing two possible visual targets.

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

    PubMed

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

    2015-08-19

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

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

    PubMed Central

    Szczepanski, Sara M.; Knight, Robert T.

    2014-01-01

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

  20. Executive Functions and Prefrontal Cortex: A Matter of Persistence?

    PubMed Central

    Ball, Gareth; Stokes, Paul R.; Rhodes, Rebecca A.; Bose, Subrata K.; Rezek, Iead; Wink, Alle-Meije; Lord, Louis-David; Mehta, Mitul A.; Grasby, Paul M.; Turkheimer, Federico E.

    2011-01-01

    Executive function is thought to originates from the dynamics of frontal cortical networks. We examined the dynamic properties of the blood oxygen level dependent time-series measured with functional MRI (fMRI) within the prefrontal cortex (PFC) to test the hypothesis that temporally persistent neural activity underlies performance in three tasks of executive function. A numerical estimate of signal persistence, the Hurst exponent, postulated to represent the coherent firing of cortical networks, was determined and correlated with task performance. Increasing persistence in the lateral PFC was shown to correlate with improved performance during an n-back task. Conversely, we observed a correlation between persistence and increasing commission error – indicating a failure to inhibit a prepotent response – during a Go/No-Go task. We propose that persistence within the PFC reflects dynamic network formation and these findings underline the importance of frequency analysis of fMRI time-series in the study of executive functions. PMID:21286223

  1. Sleep Deprivation Alters Valuation Signals in the Ventromedial Prefrontal Cortex

    PubMed Central

    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. PMID:22028686

  2. Maternal prefrontal cortex activation by newborn infant odors.

    PubMed

    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.

  3. Circuit-based Localization of Ferret Prefrontal Cortex

    PubMed Central

    Duque, Alvaro

    2010-01-01

    We examined the extent of the ferret prefrontal cortex (PFC) and its reciprocal connections with the mediodorsal nucleus of the thalamus (MD) by anterograde and retrograde labeling in 6- to 14-week-old male ferrets. Our results indicate that in the ferret, as in other species, MD projects heavily to the PFC although it also projects to other cortical and subcortical structures. The MD projection to PFC terminates largely in layer IV with lighter innervation of layers II, III, V, and VI. The cells projecting back to MD are mostly in layer VI. The parvocellular component of MD projects to and receives projections from the more caudal and dorsomedial component of the PFC, whereas the magnocellular portion of MD projects to and receives projections from the more rostral and lateral component of the PFC. With these results we have localized the ferret PFC, defined as a frontal cortical region with heavy reciprocal connections with the MD. PMID:19737780

  4. Damage to the ventromedial prefrontal cortex reduces interpersonal disgust

    PubMed Central

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

    2013-01-01

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

  5. Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia.

    PubMed

    Leitman, David I; Wolf, Daniel H; Loughead, James; Valdez, Jeffrey N; Kohler, Christian G; Brensinger, Colleen; Elliott, Mark A; Turetsky, Bruce I; Gur, Raquel E; Gur, Ruben C

    2011-01-01

    Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.

  6. Prefrontal Cortex and Somatosensory Cortex in Tactile Crossmodal Association: An Independent Component Analysis of ERP Recordings

    PubMed Central

    Wang, Liping; Lenz, Fred A.; Hsiao, Steven S.; Bodner, Mark; Hong, Bo; Zhou, Yong-Di

    2007-01-01

    Our previous studies on scalp-recorded event-related potentials (ERPs) showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA) to the ERP data, we found independent components (ICs) located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC) and the primary somatosensory cortex (SI). The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex) that are involved in sensation and perception of various stimuli. PMID:17712419

  7. Improving memory following prefrontal cortex damage with the PQRST method

    PubMed Central

    Ciaramelli, Elisa; Neri, Francesco; Marini, Luca; Braghittoni, Davide

    2015-01-01

    We tested (1) whether the PQRST method, involving Preview (P), Question (Q), Read (R), State (S), and Test (T) phases, is effective in enhancing long-term memory in patients with mild memory problems due to prefrontal cortex lesions, and (2) whether patients also benefit from a more self-initiated version of the PQRST. Seven patients with prefrontal lesions encoded new texts under three different conditions: the Standard condition, requiring to read texts repeatedly, the PQRST-Other condition, in which the experimenter formulated questions about the text (Q phase), and the PQRST-Self condition, in which patients formulated the relevant questions on their own. Compared to the Standard condition, both the PQRST-Other and the PQRST-Self condition resulted in higher immediate and delayed recall rates, as well as a higher ability to answer questions about the texts. Importantly, the two PQRST conditions did not differ in efficacy. These results confirm that the PQRST method is effective in improving learning of new material in brain-injured populations with mild memory problems. Moreover, they indicate that the PQRST proves effective even under conditions with higher demands on patients’ autonomy and self-initiation, which encourages its application to real-life situations. PMID:26321932

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

    PubMed

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

    2012-01-01

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

  9. Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion

    PubMed Central

    McKlveen, Jessica M.; Myers, Brent; Flak, Jonathan N.; Bundzikova, Jana; Solomon, Matia B.; Seroogy, Kim B.; Herman, James P.

    2013-01-01

    Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation. Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field. Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyper-locomotion in the open field, but did not affect stress sensitization or helplessness behavior. Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation. PMID:23683655

  10. Medial Prefrontal Cortex Activation Is Commonly Invoked by Reputation of Self and Romantic Partners

    PubMed Central

    Kawamichi, Hiroaki; Sasaki, Akihiro T.; Matsunaga, Masahiro; Yoshihara, Kazufumi; Takahashi, Haruka K.; Tanabe, Hiroki C.; Sadato, Norihiro

    2013-01-01

    The reputation of others influences partner selection in human cooperative behaviors through verbal reputation representation. Although the way in which humans represent the verbal reputations of others is a pivotal issue for social neuroscience, the neural correlates underlying the representation of verbal reputations of others are unclear. Humans primarily depend on self-evaluation when assessing reputation of self. Likewise, humans might primarily depend on self-evaluation of others when representing their reputation. As interaction promotes the formation of more nuanced, individualized impressions of an interaction partner, humans tend to form self-evaluations of persons with whom they are intimate in their daily life. Thus, we hypothesized that the representation of reputation of others is modulated by intimacy due to one’s own evaluation formation of that person. To test this hypothesis, we conducted a functional magnetic resonance imaging experiment with 11 pairs of romantic partners while they viewed an evaluation of a target person (self, partner [intimate other], or stranger [non-intimate other]), made by other evaluators. When compared with strangers, viewing evaluations of self and partner activated overlapping regions in the medial prefrontal cortex. Verbal reputation of self-specific activation was found in the precuneus, which represents self-related processing. The data suggest that midline structures represent reputation of self. In addition, intimacy-modulated activation in the medial prefrontal cortex suggests that the verbal reputation of intimate others is represented similarly to reputation of self. These results suggest that the reputation representation in the medial prefrontal cortex is engaged by verbal reputation of self and intimate others stemming from both own and other evaluators’ judgments. PMID:24086409

  11. Medial prefrontal cortex activation is commonly invoked by reputation of self and romantic partners.

    PubMed

    Kawamichi, Hiroaki; Sasaki, Akihiro T; Matsunaga, Masahiro; Yoshihara, Kazufumi; Takahashi, Haruka K; Tanabe, Hiroki C; Sadato, Norihiro

    2013-01-01

    The reputation of others influences partner selection in human cooperative behaviors through verbal reputation representation. Although the way in which humans represent the verbal reputations of others is a pivotal issue for social neuroscience, the neural correlates underlying the representation of verbal reputations of others are unclear. Humans primarily depend on self-evaluation when assessing reputation of self. Likewise, humans might primarily depend on self-evaluation of others when representing their reputation. As interaction promotes the formation of more nuanced, individualized impressions of an interaction partner, humans tend to form self-evaluations of persons with whom they are intimate in their daily life. Thus, we hypothesized that the representation of reputation of others is modulated by intimacy due to one's own evaluation formation of that person. To test this hypothesis, we conducted a functional magnetic resonance imaging experiment with 11 pairs of romantic partners while they viewed an evaluation of a target person (self, partner [intimate other], or stranger [non-intimate other]), made by other evaluators. When compared with strangers, viewing evaluations of self and partner activated overlapping regions in the medial prefrontal cortex. Verbal reputation of self-specific activation was found in the precuneus, which represents self-related processing. The data suggest that midline structures represent reputation of self. In addition, intimacy-modulated activation in the medial prefrontal cortex suggests that the verbal reputation of intimate others is represented similarly to reputation of self. These results suggest that the reputation representation in the medial prefrontal cortex is engaged by verbal reputation of self and intimate others stemming from both own and other evaluators' judgments.

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

    PubMed Central

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

    2016-01-01

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

  13. Exon Microarray Analysis of Human Dorsolateral Prefrontal Cortex in Alcoholism

    PubMed Central

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

    2014-01-01

    Background Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Methods Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC, Brodmann area 9) of 7 adult Alcoholic (6 males, 1 female, mean age 48 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST Array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using qRT-PCR, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Results Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN) and signaling (e.g., RASGRP, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease, and development including cellular assembly and organization impacting on psychological disorders. Conclusions Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation and signaling that targets white matter of the brain. PMID:24890784

  14. Ventromedial prefrontal cortex and the regulation of physiological arousal

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex.

    PubMed

    Bryden, Daniel W; Burton, Amanda C; Barnett, Brian R; Cohen, Valerie J; Hearn, Taylor N; Jones, Emily A; Kariyil, Reshma J; Kunin, Alice; Kwak, Sae In; Lee, Jessica; Lubinski, Brooke L; Rao, Gautam K; Zhan, Ashley; Roesch, Matthew R

    2016-02-01

    Prenatal nicotine exposure (PNE) is linked to numerous psychiatric disorders including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex. Yet, it is unclear how neural activity in the medial prefrontal cortex (mPFC) is modulated during tasks that assess response inhibition or if these neural correlates, along with behavior, are affected by PNE. To address this issue, we recorded from single mPFC neurons in control and PNE rats as they performed a stop-signal task. We found that PNE rats were faster for all trial-types, made more premature responses, and were less likely to inhibit behavior on 'STOP' trials during which rats had to inhibit an already initiated response. Activity in mPFC was modulated by response direction and was positively correlated with accuracy and movement time in control but not PNE rats. Although the number of single neurons correlated with response direction was significantly reduced by PNE, neural activity observed on general STOP trials was largely unaffected. However, dramatic behavioral deficits on STOP trials immediately following non-conflicting (GO) trials in the PNE group appear to be mediated by the loss of conflict monitoring signals in mPFC. We conclude that prenatal nicotine exposure makes rats impulsive and disrupts firing of mPFC neurons that carry signals related to response direction and conflict monitoring.

  19. The role of the dorsolateral prefrontal cortex in early threat processing: a TMS study.

    PubMed

    Sagliano, Laura; D'Olimpio, Francesca; Panico, Francesco; Gagliardi, Serena; Trojano, Luigi

    2016-12-01

    Previous studies demonstrated that excitatory (high frequency) offline transcranial magnetic stimulation (TMS) over the left and right dorsolateral prefrontal cortex (DLPFC) modulates attention allocation on threatening stimuli in non-clinical samples. These studies only employed offline TMS protocol that did not allow investigating the effect of the stimulation on the early stage of threat processing. In this study, the role of the right and left dorsolateral prefrontal cortex in early threat processing was investigated in high and low anxious individuals by means of an inhibitory single-pulse online TMS protocol. Our results demonstrated the role of the left DLPFC in an early stage of threat processing and that this effect is modulated by individuals' anxiety level. The inhibitory stimulation of the left DLPFC determined a disengagement bias in high anxious individuals, while the same stimulation determined an attentional avoidance in low anxious individuals. The findings of the present study suggest that right and left DLPFC are differently involved in early threat processing of healthy individuals.

  20. Demonstration of short-term plasticity in the dorsolateral prefrontal cortex with theta burst stimulation: A TMS-EEG study.

    PubMed

    Chung, Sung Wook; Lewis, Benjamin P; Rogasch, Nigel C; Saeki, Takashi; Thomson, Richard H; Hoy, Kate E; Bailey, Neil W; Fitzgerald, Paul B

    2017-07-01

    To examine the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) on cortical reactivity in the dorsolateral prefrontal cortex. 10 healthy participants were stimulated with either iTBS, cTBS or sham at F3 electrode. Single- and paired-pulse TMS and concurrent electroencephalography (EEG) were used to assess change in cortical reactivity and long-interval intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked oscillations. Significant increases in N120 amplitudes (p<0.01) were observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta oscillations and LICI of theta oscillations were also observed following iTBS (increase) and cTBS (decrease). Change in LICI of theta oscillations correlated with change in N120 amplitude following TBS (r=-0.670, p=0.001). This study provides preliminary evidence that TBS produces direct changes in cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a useful approach to optimise stimulation paradigms prior to the conduct of clinical trials. TBS is able to modulate cortical reactivity and cortical inhibition in the prefrontal cortex. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2015-10-01

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

  2. Prefrontal cortex white matter tracts in prodromal Huntington disease

    PubMed Central

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

    2015-01-01

    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 (ATR), 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. PMID:26179962

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

    PubMed

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

    2013-03-01

    While it is well accepted that the left prefrontal cortex plays a critical role in planning and problem-solving tasks, very little is known about the role of the right prefrontal cortex. We addressed this issue by testing five neurological patients with focal lesions to right prefrontal cortex on a real-world travel planning task, and compared their performance with the performance of five neurological patients with focal lesions to left prefrontal cortex, five neurological patients with posterior lesions, and five normal controls. Only patients with lesions to right prefrontal cortex generated substandard solutions compared to normal controls. Examination of the underlying cognitive processes and strategies revealed that patients with lesions to right prefrontal cortex approached the task at an excessively precise, concrete level compared to normal controls, and very early locked themselves into substandard solutions relative to the comparison group. In contrast, the behavior of normal controls was characterized by a judicious interplay of concrete and abstract levels/modes of representations. We suggest that damage to the right prefrontal system impairs the encoding and processing of more abstract and vague representations that facilitate lateral transformations, resulting in premature commitment to precise concrete patterns, and hasty albeit substandard conclusions (because the space of possibilities has not been properly explored). Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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.

  6. Prefrontal Cortex to Accumbens Projections in Sleep Regulation of Reward

    PubMed Central

    Liu, Zheng; Wang, Yao; Cai, Li; Li, Yizhi; Chen, Bo; Dong, Yan

    2016-01-01

    Sleep profoundly affects the emotional and motivational state. In humans and animals, loss of sleep often results in enhanced motivation for reward, which has direct implications for health risks as well as potential benefits. Current study aims at understanding the mechanisms underlying sleep deprivation (SDe)-induced enhancement of reward seeking. We found that after acute SDe, mice had an increase in sucrose seeking and consumption but not food intake, suggesting a selective enhancement of motivation for reward. In the nucleus accumbens (NAc), a key brain region regulating emotional and motivational responses, we observed a decrease in the ratio of the overall excitatory over inhibitory synaptic inputs onto NAc principle neurons after SDe. The shift was partly mediated by reduced glutamatergic transmission of presynaptic origin. Further analysis revealed that there was selective reduction of the glutamate release probability at the medial prefrontal cortex (mPFC)-to-NAc synapses, but not those from the hippocampus, thalamus, or the basal lateral amygdala. To reverse this SDe-induced synaptic alteration, we expressed the stabilized step function opsin (SSFO) in the mPFC; optogenetic stimulation of SSFO at mPFC-to-NAc projection terminals persistently enhanced the action potential-dependent glutamate release. Intra-NAc optogenetic stimulation of SSFO selectively at mPFC-to-NAc terminals restored normal sucrose seeking in mice after SDe without affecting food intake. These results highlight the mPFC-to-NAc projection as a key circuit-based target for sleep to regulate reward-motivated behaviors. SIGNIFICANCE STATEMENT Sleep loss, a costly challenge of modern society, has profound physiological and psychological consequences, including altered reward processing of the brain. The current study aims at understanding the mechanisms underlying sleep deprivation-induced enhancement of reward seeking. We identify that the medial prefrontal cortex (m

  7. Prefrontal Cortex to Accumbens Projections in Sleep Regulation of Reward.

    PubMed

    Liu, Zheng; Wang, Yao; Cai, Li; Li, Yizhi; Chen, Bo; Dong, Yan; Huang, Yanhua H

    2016-07-27

    Sleep profoundly affects the emotional and motivational state. In humans and animals, loss of sleep often results in enhanced motivation for reward, which has direct implications for health risks as well as potential benefits. Current study aims at understanding the mechanisms underlying sleep deprivation (SDe)-induced enhancement of reward seeking. We found that after acute SDe, mice had an increase in sucrose seeking and consumption but not food intake, suggesting a selective enhancement of motivation for reward. In the nucleus accumbens (NAc), a key brain region regulating emotional and motivational responses, we observed a decrease in the ratio of the overall excitatory over inhibitory synaptic inputs onto NAc principle neurons after SDe. The shift was partly mediated by reduced glutamatergic transmission of presynaptic origin. Further analysis revealed that there was selective reduction of the glutamate release probability at the medial prefrontal cortex (mPFC)-to-NAc synapses, but not those from the hippocampus, thalamus, or the basal lateral amygdala. To reverse this SDe-induced synaptic alteration, we expressed the stabilized step function opsin (SSFO) in the mPFC; optogenetic stimulation of SSFO at mPFC-to-NAc projection terminals persistently enhanced the action potential-dependent glutamate release. Intra-NAc optogenetic stimulation of SSFO selectively at mPFC-to-NAc terminals restored normal sucrose seeking in mice after SDe without affecting food intake. These results highlight the mPFC-to-NAc projection as a key circuit-based target for sleep to regulate reward-motivated behaviors. Sleep loss, a costly challenge of modern society, has profound physiological and psychological consequences, including altered reward processing of the brain. The current study aims at understanding the mechanisms underlying sleep deprivation-induced enhancement of reward seeking. We identify that the medial prefrontal cortex (mPFC)-to-nucleus accumbens (NAc) glutamatergic

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

    PubMed Central

    McGarry, Laura M.

    2016-01-01

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

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

    PubMed

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

    2017-05-10

    Selective attention is known to interact with perceptual organization. In visual scenes, individual objects that are distinct and discriminable may occur on their own, or in groups such as a stack of books. The main objective of this study is to probe the neural interaction that occurs between individual objects when attention is directed toward one or more objects. Here we record steady-state visual evoked potentials via electrocorticography to directly assess the responses to individual stimuli and to their interaction. When human participants attend to two adjacent stimuli, prefrontal and parietal cortex shows a selective enhancement of only the neural interaction between stimuli, but not the responses to individual stimuli. When only one stimulus is attended, the neural response to that stimulus is selectively enhanced in prefrontal and parietal cortex. In contrast, early visual areas generally manifest responses to individual stimuli and to their interaction regardless of attentional task, although a subset of the responses is modulated similarly to prefrontal and parietal cortex. Thus, the neural representation of the visual scene as one progresses up the cortical hierarchy becomes more highly task-specific and represents either individual stimuli or their interaction, depending on the behavioral goal. Attention to multiple objects facilitates an integration of objects akin to perceptual grouping.SIGNIFICANCE STATEMENT Individual objects in a visual scene are seen as distinct entities or as parts of a whole. Here we examine how attention to multiple objects affects their neural representation. Previous studies measured single-cell or fMRI responses and obtained only aggregate measures that combined the activity to individual stimuli as well as their potential interaction. Here, we directly measure electrocorticographic steady-state responses corresponding to individual objects and to their interaction using a frequency-tagging technique. Attention to two

  10. Psychostimulants Act within the Prefrontal Cortex to Improve Cognitive Function

    PubMed Central

    Spencer, Robert C.; Klein, Raymond M.; Berridge, Craig W.

    2011-01-01

    Background At low and clinically-relevant doses, psychostimulants enhance cognitive and behavioral function dependent on the prefrontal cortex (PFC) and extended frontostriatal circuitry. These actions are observed in individuals with attention deficit hyperactivity disorder (ADHD) as well as in normal human and animal subjects. Despite the widespread use of these drugs, the sites of action involved in their cognition-enhancing and therapeutic effects are poorly understood. Indirect and/or correlative evidence suggests the cognition-enhancing/therapeutic effects of psychostimulants may involve actions directly within the PFC or extended frontostriatal circuitry. The current studies examined the degree to which methylphenidate (MPH; Ritalin®) acts within distinct frontostriatal subfields to improve PFC-dependent cognition as measured in a delayed-response test of spatial working memory. Methods Working memory performance was assessed following microinfusion of vehicle or varying doses of MPH (0.03-8.0 μg/500 nl) directly into the dorsomedial PFC (dorsal prelimbic and dorsal anterior cingulate cortex), the ventromedial PFC (infralimbic) and the dorsomedial striatum of rats (n=69). Results MPH infusion into the dorsomedial PFC, but not ventromedial PFC, elicited an inverted-U shaped facilitation of PFC-dependent cognition as measured in this task. The magnitude of this improvement was comparable to that seen with systemic administration. Additional studies demonstrated that although the dorsomedial striatum is necessary for accurate performance in this task, MPH infusion into this region did not affect working memory performance. Conclusions These observations provide the first definitive evidence that the PFC is a site of action in the cognition-enhancing and presumably therapeutic actions of low-dose psychostimulants. PMID:22209638

  11. microRNA Profiles in Parkinson's Disease Prefrontal Cortex

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-06-01

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

  13. Impact of anxiety on prefrontal cortex encoding of cognitive flexibility.

    PubMed

    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.

  14. Reward value comparison via mutual inhibition in ventromedial prefrontal cortex

    PubMed Central

    Strait, Caleb E.; Blanchard, Tommy C.; Hayden, Benjamin Y.

    2014-01-01

    Recent theories suggest that reward-based choice reflects competition between value signals in the ventromedial prefrontal cortex (vmPFC). We tested this idea by recording vmPFC neurons while macaques performed a gambling task with asynchronous offer presentation. We found that neuronal activity shows four patterns consistent with selection via mutual inhibition. (1) Correlated tuning for probability and reward size, suggesting that vmPFC carries an integrated value signal, (2) anti-correlated tuning curves for the two options, suggesting mutual inhibition, (3) neurons rapidly come to signal the value of the chosen offer, suggesting the circuit serves to produce a choice, (4) after regressing out the effects of option values, firing rates still could predict choice – a choice probability signal. In addition, neurons signaled gamble outcomes, suggesting that vmPFC contributes to both monitoring and choice processes. These data suggest a possible mechanism for reward-based choice and endorse the centrality of vmPFC in that process. PMID:24881835

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

    PubMed

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

    2015-07-14

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

  16. Architecture of Explanatory Inference in the Human Prefrontal Cortex

    PubMed Central

    Barbey, Aron K.; Patterson, Richard

    2011-01-01

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

  17. Inhibitory deficits in the dorsolateral prefrontal cortex in psychopathic offenders.

    PubMed

    Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Stirpe, Tania; Fitzgerald, Paul B; Voineskos, Aristotle N; Schutter, Dennis J L G; Daskalakis, Zafiris J

    2013-05-01

    Often typified as cunning social predators, psychopathic offenders show a persistent pattern of impulsive and reckless behavior, the pathophysiology of which has been related to dysfunction in the dorsolateral prefrontal cortex (DLPFC). That is, the DLPFC is important for the regulatory control of impulses and emotion as well as working memory and psychopathic offenders show impairments in all three dimensions. In the present study, we used combined transcranial magnetic stimulation and electroencephalography to compare the physiology of the DLPFC in 13 psychopathic offenders and 15 healthy subjects vis à vis excitability and inhibition. In addition, working memory performance was measured through the letter-number sequencing test. Results showed that compared to healthy subjects, psychopathic offenders had inhibition not excitability deficits in the DLPFC that was accompanied by deficits in working memory performance. In healthy controls and psychopathic offenders working memory performance correlated with the extent of inhibition over the DLPFC. Taken together, these findings suggest that psychopathic offenders suffer from dysfunctional inhibitory neurotransmission in the DLPFC and impaired working memory which may account for the behavioral impairments associated with this disorder. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Disrupting the right prefrontal cortex alters moral judgement.

    PubMed

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

    2012-03-01

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

  19. Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding.

    PubMed

    Guise, Kevin G; Shapiro, Matthew L

    2017-04-05

    The prefrontal cortex (PFC) is crucial for accurate memory performance when prior knowledge interferes with new learning, but the mechanisms that minimize proactive interference are unknown. To investigate these, we assessed the influence of medial PFC (mPFC) activity on spatial learning and hippocampal coding in a plus maze task that requires both structures. mPFC inactivation did not impair spatial learning or retrieval per se, but impaired the ability to follow changing spatial rules. mPFC and CA1 ensembles recorded simultaneously predicted goal choices and tracked changing rules; inactivating mPFC attenuated CA1 prospective coding. mPFC activity modified CA1 codes during learning, which in turn predicted how quickly rats adapted to subsequent rule changes. The results suggest that task rules signaled by the mPFC become incorporated into hippocampal representations and support prospective coding. By this mechanism, mPFC activity prevents interference by "teaching" the hippocampus to retrieve distinct representations of similar circumstances.

  20. Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex

    PubMed Central

    McEwen, Bruce S; Nasca, Carla; Gray, Jason D

    2016-01-01

    The hippocampus provided the gateway into much of what we have learned about stress and brain structural and functional plasticity, and this initial focus has expanded to other interconnected brain regions, such as the amygdala and prefrontal cortex. Starting with the discovery of adrenal steroid, and later, estrogen receptors in the hippocampal formation, and subsequent discovery of dendritic and spine synapse remodeling and neurogenesis in the dentate gyrus, mechanistic studies have revealed both genomic and rapid non-genomic actions of circulating steroid hormones in the brain. Many of these actions occur epigenetically and result in ever-changing patterns of gene expression, in which there are important sex differences that need further exploration. Moreover, glucocorticoid and estrogen actions occur synergistically with an increasing number of cellular mediators that help determine the qualitative nature of the response. The hippocampus has also been a gateway to understanding lasting epigenetic effects of early-life experiences. These findings in animal models have resulted in translation to the human brain and have helped change thinking about the nature of brain malfunction in psychiatric disorders and during aging, as well as the mechanisms of the effects of early-life adversity on the brain and the body. PMID:26076834

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

    PubMed Central

    Morrison, Samantha

    2014-01-01

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

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

    PubMed

    Barbey, Aron K; Patterson, Richard

    2011-01-01

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

  3. Regulation of prefrontal cortex myelination by the microbiota.

    PubMed

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

    2016-04-05

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

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

    PubMed

    Molenberghs, Pascal; Morrison, Samantha

    2014-03-01

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

  5. Do sex differences affect prefrontal cortex associated cognition in schizophrenia?

    PubMed

    Roesch-Ely, Daniela; Hornberger, Eva; Weiland, Stephan; Hornstein, Christiane; Parzer, Peter; Thomas, Christine; Weisbrod, Matthias

    2009-02-01

    Cognitive deficits in schizophrenia, especially those related to prefrontal cortex (PFC) functions, influence functional outcome. There is evidence for sex differences in cognition in schizophrenia, but the results in the literature are still controversial. This study evaluated different modalities of working memory (WM) and executive control (EC), functions that are both associated with the PFC, between sexes in schizophrenic patients and controls. We used a battery of neuropsychological tests for assessing auditory, spatial, and visual-matching WM and used a dual task for assessing EC. The study included 50 inpatients (25 female) partially remitted and taking atypical neuroleptics, as well as 40 controls (20 female) matched for age and education. Significant sex differences were found in the dual task; female patients detected fewer correct trials than male patients and controls did. Moreover, female patients performed significantly worse in the single visual subtest of the dual task. For the controls, no sex differences were found. Males showed higher positive symptoms than females, but no other differences in psychopathology, disease characteristics, or extrapyramidal symptoms were found between sexes. The present study shows an absence of sex differences in WM in healthy subjects and in patients with schizophrenia. However, in the dual task and in the single visual subtest, female patients performed worse than males. This finding suggests that in contrast to males, nonacute female inpatients show an underlying attentional deficit that may contribute to impairment in higher-order functions such as EC.

  6. Regulation of prefrontal cortex myelination by the microbiota

    PubMed Central

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

    2016-01-01

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

  7. Reward value comparison via mutual inhibition in ventromedial prefrontal cortex.

    PubMed

    Strait, Caleb E; Blanchard, Tommy C; Hayden, Benjamin Y

    2014-06-18

    Recent theories suggest that reward-based choice reflects competition between value signals in the ventromedial prefrontal cortex (vmPFC). We tested this idea by recording vmPFC neurons while macaques performed a gambling task with asynchronous offer presentation. We found that neuronal activity shows four patterns consistent with selection via mutual inhibition: (1) correlated tuning for probability and reward size, suggesting that vmPFC carries an integrated value signal; (2) anti-correlated tuning curves for the two options, suggesting mutual inhibition; (3) neurons rapidly come to signal the value of the chosen offer, suggesting the circuit serves to produce a choice; and (4) after regressing out the effects of option values, firing rates still could predict choice-a choice probability signal. In addition, neurons signaled gamble outcomes, suggesting that vmPFC contributes to both monitoring and choice processes. These data suggest a possible mechanism for reward-based choice and endorse the centrality of vmPFC in that process. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. A general role for medial prefrontal cortex in event prediction

    PubMed Central

    Alexander, William H.; Brown, Joshua W.

    2014-01-01

    A recent computational neural model of medial prefrontal cortex (mPFC), namely the predicted response-outcome (PRO) model (Alexander and Brown, 2011), suggests that mPFC learns to predict the outcomes of actions. The model accounted for a wide range of data on the mPFC. Nevertheless, numerous recent findings suggest that mPFC may signal predictions and prediction errors even when the predicted outcomes are not contingent on prior actions. Here we show that the existing PRO model can learn to predict outcomes in a general sense, and not only when the outcomes are contingent on actions. A series of simulations show how this generalized PRO model can account for an even broader range of findings in the mPFC, including human ERP, fMRI, and macaque single-unit data. The results suggest that the mPFC learns to predict salient events in general and provides a theoretical framework that links mPFC function to model-based reinforcement learning, Bayesian learning, and theories of cognitive control. PMID:25071539

  9. Lie-specific involvement of dorsolateral prefrontal cortex in deception.

    PubMed

    Priori, Alberto; Mameli, F; Cogiamanian, F; Marceglia, S; Tiriticco, M; Mrakic-Sposta, S; Ferrucci, R; Zago, S; Polezzi, D; Sartori, G

    2008-02-01

    Lies are intentional distortions of event knowledge. No experimental data are available on manipulating lying processes. To address this issue, we stimulated the dorsolateral prefrontal cortex (DLPFC) using transcranial direct current stimulation (tDCS). Fifteen healthy volunteers were tested before and after tDCS (anodal, cathodal, and sham). Two types of truthful (truthful selected: TS; truthful unselected: TU) and deceptive (lie selected: LS; lie unselected: LU) responses were evaluated using a computer-controlled task. Reaction times (RTs) and accuracy were collected and used as dependent variables. In the baseline task, the RT was significantly longer for lie responses than for true responses ([mean +/- standard error] 1153.4 +/- 42.0 ms vs. 1039.6 +/- 36.6 ms; F(1,14) = 27.25, P = 0.00013). At baseline, RT for selected pictures was significantly shorter than RT for unselected pictures (1051.26 +/- 39.0 ms vs. 1141.76 +/- 41.1 ms; F(1,14) = 34.85, P = 0.00004). Whereas after cathodal and sham stimulation, lie responses remained unchanged (cathodal 5.26 +/- 2.7%; sham 5.66 +/- 3.6%), after anodal tDCS, RTs significantly increased but did so only for LS responses (16.86 +/- 5.0%; P = 0.002). These findings show that manipulation of brain function with DLPFC tDCS specifically influences experimental deception and that distinctive neural mechanisms underlie different types of lies.

  10. Nature experience reduces rumination and subgenual prefrontal cortex activation

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

  12. Proinflammatory Cytokines in the Prefrontal Cortex of Teenage Suicide Victims

    PubMed Central

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

    2011-01-01

    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. PMID:21906753

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

    PubMed

    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.

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

    ERIC Educational Resources Information Center

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

    1997-01-01

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

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

    ERIC Educational Resources Information Center

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

    1997-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. The lateral prefrontal cortex mediates the hyperalgesic effects of negative cognitions in chronic pain patients

    PubMed Central

    Loggia, Marco L.; Berna, Chantal; Kim, Jieun; Cahalan, Christine M.; Martel, Marc-Olivier; Gollub, Randy L.; Wasan, Ajay D.; Napadow, Vitaly; Edwards, Robert R.

    2015-01-01

    While high levels of negative affect and cognitions have been associated in chronic pain conditions with greater pain sensitivity, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation, and that 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing, in fibromyalgia (FM) patients. Using functional Magnetic Resonance Imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex (IPFC). A bootstrapped mediation analysis revealed that pain-anticipatory activity in lateral prefrontal cortex (IPFC) mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of IPFC in the pathophysiology of FM related hyperalgesia, and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well validated measure of negative cognitions and psychological distress. Perspective This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neurofeedback-based techniques aimed at modifying patients' negative affect and cognitions towards pain. PMID:25937162

  18. Cathodal tDCS over the left prefrontal cortex diminishes choice-induced preference change.

    PubMed

    Mengarelli, Flavia; Spoglianti, Silvia; Avenanti, Alessio; di Pellegrino, Giuseppe

    2015-05-01

    In everyday life, people often find themselves facing difficult decisions between options that are equally attractive. Cognitive dissonance theory states that after making a difficult choice between 2 equally preferred options, individuals no longer find the alternatives similarly desirable. Rather, they often change their existing preferences to align more closely with the choice they have just made. Despite the relevance of cognitive dissonance in modulating behavior, little is known about the brain processes crucially involved in choice-induced preference change. In the present study, we applied cathodal transcranial Direct Current Stimulation (tDCS) with the aim of downregulating the activity of the left or the right dorsolateral prefrontal cortex (DLPFC) during a revised version of Brehm's (in 1956. Post-decision changes in the desirability of alternatives. J Abnorm Soc Psychol. 52:384-389) free-choice paradigm. We found that cathodal tDCS over the left, but not over the right, DLPFC caused a reduction of the typical behavior-induced preference change relative to sham stimulation. Our findings highlight the role of prefrontal cortex in cognitive dissonance and provide evidence that left DLPFC plays a necessary role in the implementation of choice-induced preference change. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

    PubMed Central

    Gacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae G; Tamburini, Sabrina; Andrade, Monica; Zhang, Fan; Shen, Nan; Tolstikov, Vladimir; Kiebish, Michael A; Dupree, Jeffrey L; Zachariou, Venetia; Clemente, Jose C; Casaccia, Patrizia

    2016-01-01

    Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior. DOI: http://dx.doi.org/10.7554/eLife.13442.001 PMID:27097105

  20. Prelimbic prefrontal cortex mediates respiratory responses to mild and potent prolonged, but not brief, stressors.

    PubMed

    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.

  1. Plasticity at hippocampal to prefrontal cortex synapses: dual roles in working memory and consolidation.

    PubMed

    Laroche, S; Davis, S; Jay, T M

    2000-01-01

    The involvement of the hippocampus and the prefrontal cortex in cognitive processes and particularly in learning and memory has been known for a long time. However, the specific role of the projection which connects these two structures has remained elusive. The existence of a direct monosynaptic pathway from the ventral CA1 region of the hippocampus and subiculum to specific areas of the prefrontal cortex provides a useful model for conceptualizing the functional operations of hippocampal-prefrontal cortex communication in learning and memory. It is known now that hippocampal to prefrontal cortex synapses are modifiable synapses and can express different forms of plasticity, including long-term potentiation, long-term depression, and depotentiation. Here we review these findings and focus on recent studies that start to relate synaptic plasticity in the hippocampo-prefrontal cortex pathway to two specific aspects of learning and memory, i.e., the consolidation of information and working memory. The available evidence suggests that functional interactions between the hippocampus and prefrontal cortex in cognition and memory are more complex than previously anticipated, with the possibility for bidirectional regulation of synaptic strength as a function of the specific demands of tasks.

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

    PubMed

    Moriya, M; Aoki, C; Sakatani, K

    2016-01-01

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

  3. Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal-prefrontal coherence.

    PubMed

    Insel, Nathan; Pilkiw, Maryna; Nobrega, José N; Hutchison, William D; Takehara-Nishiuchi, Kaori; Hamani, Clement

    2015-07-01

    Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation.

  4. Aversive learning in adolescents: modulation by amygdala-prefrontal and amygdala-hippocampal connectivity and neuroticism.

    PubMed

    Tzschoppe, Jelka; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J; Büchel, Christian; Conrod, Patricia J; Garavan, Hugh; Heinz, Andreas; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Smolka, Michael N; Gallinat, Jürgen; Ströhle, Aandreas; Struve, Maren; Rietschel, Marcella; Schumann, Gunter; Flor, Herta

    2014-03-01

    Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS- never followed by the US). During acquisition (CS+/- differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders.

  5. Aversive Learning in Adolescents: Modulation by Amygdala–Prefrontal and Amygdala–Hippocampal Connectivity and Neuroticism

    PubMed Central

    Tzschoppe, Jelka; Nees, Frauke; Banaschewski, Tobias; Barker, Gareth J; Büchel, Christian; Conrod, Patricia J; Garavan, Hugh; Heinz, Andreas; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Smolka, Michael N; Gallinat, Jürgen; Ströhle, Aandreas; Struve, Maren; Rietschel, Marcella; Schumann, Gunter; Flor, Herta

    2014-01-01

    Neuroticism involves a tendency for enhanced emotional and cognitive processing of negative affective stimuli and a propensity to worry and be anxious. It is known that this trait modulates fear learning and the activation of brain regions involved in it such as the amygdala, hippocampus, and prefrontal cortex and their connectivity. Thirty-nine (21 female) 14-year-old healthy adolescents participated in functional magnetic resonance imaging (fMRI) of aversive pavlovian differential delay conditioning. An unpleasant sound served as unconditioned stimulus (US) and pictures of neutral male faces as conditioned stimuli (CS+ followed by the US in 50% of the cases; CS− never followed by the US). During acquisition (CS+/− differentiation), higher levels of neuroticism were associated with a stronger interaction between the right amygdala and the right hippocampus as well as the right amygdala and prefrontal cortical regions, specifically ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate cortex. The association of stronger conditionability of fear and connectivity of brain regions related to consolidation of fear associations and neuroticism points to underlying mechanisms of the enhanced propensity for anxiety disorders in highly neurotic participants. This is especially important in adolescence, a vulnerable time for the onset of mental disorders such as anxiety disorders. PMID:24126454

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

    PubMed Central

    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

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

    PubMed

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

    2016-07-01

    A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Auditory belt and parabelt projections to the prefrontal cortex in the rhesus monkey.

    PubMed

    Romanski, L M; Bates, J F; Goldman-Rakic, P S

    1999-01-11

    Recent anatomical and electrophysiological studies have expanded our knowledge of the auditory cortical system in primates and have described its organization as a series of concentric circles with a central or primary auditory core, surrounded by a lateral and medial belt of secondary auditory cortex with a tertiary parabelt cortex just lateral to this belt. Because recent studies have shown that rostral and caudal belt and parabelt cortices have distinct patterns of connections and acoustic responsivity, we hypothesized that these divergent auditory regions might have distinct targets in the frontal lobe. We, therefore, placed discrete injections of wheat germ agglutinin-horseradish peroxidase or fluorescent retrograde tracers into the prefrontal cortex of macaque monkeys and analyzed the anterograde and retrograde labeling in the aforementioned auditory areas. Injections that included rostral and orbital prefrontal areas (10, 46 rostral, 12) labeled the rostral belt and parabelt most heavily, whereas injections including the caudal principal sulcus (area 46), periarcuate cortex (area 8a), and ventrolateral prefrontal cortex (area12vl) labeled the caudal belt and parabelt. Projections originating in the parabelt cortex were denser than those arising from the lateral or medial belt cortices in most cases. In addition, the anterior third of the superior temporal gyrus and the dorsal bank of the superior temporal sulcus were also labeled after prefrontal injections, confirming previous studies. The present topographical results suggest that acoustic information diverges into separate streams that target distinct rostral and caudal domains of the prefrontal cortex, which may serve different acoustic functions.

  9. Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder

    PubMed Central

    Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

    2017-01-01

    Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the ‘responsivity’ of the E–I system to pharmacologic challenge; or whether E–I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E–I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal ‘Inhibitory Index’—the GABA fraction within the pool of glutamate plus GABA metabolites—post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E–I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E–I flux can be ‘shifted’ with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be ‘normalised’ by targeting E–I, even in adults. PMID:28534874

  10. Involvement of the prefrontal cortex in problem solving.

    PubMed

    Mushiake, Hajime; Sakamoto, Kazuhiro; Saito, Naohiro; Inui, Toshiro; Aihara, Kazuyuki; Tanji, Jun

    2009-01-01

    To achieve a behavioral goal in a complex environment, such as problem-solving situations, we must plan multiple steps of action. On planning a series of actions, we anticipate future events that will occur as a result of each action, and mentally organize the temporal sequence of events. To investigate the involvement of the lateral prefrontal cortex (PFC) in such multistep planning, we examined neuronal activity in the PFC while monkeys performed a maze path-finding task. In this task, we set monkeys the job of capturing a goal in the maze by moving a cursor on the screen. Cursor movement was linked to movements of each wrist. To dissociate the outcomes of the intended action from the motor commands, we trained the monkeys to use three different hand-cursor assignments. We found that monkeys were able to perform this task in a flexible manner. This report first introduces a problem-solving framework for studying the function of the PFC, from the view point of cognitive science. Then, this chapter will cover the neuronal representation of a series of actions, goal subgoal transformation, and synchrony of PFC neurons. We reported PFC neurons reflected final goals and immediate goals during the preparatory period. We also found some PFC neurons reflected each of all forthcoming steps of actions during the preparatory period and increased their activity step by step during the execution period. Recently, we found that the transient increase in synchronous activity of PFC neurons was involved in goal subgoal transformations. Our data suggest that the PFC is involved primarily in the dynamic representation of multiple future events that occur as a consequence of behavioral actions in problem-solving situations.

  11. Ventromedial Prefrontal Cortex Thinning in Preschool-Onset Depression

    PubMed Central

    Marrus, Natasha; Belden, Andrew; Nishino, Tomoyuki; Handler, Ted; Ratnanather, J Tilak; Miller, Michael; Barch, Deanna; Luby, Joan; Botteron, Kelly

    2016-01-01

    Background The ventromedial prefrontal cortex (VMPFC) is a key center of affect regulation and processing, fundamental aspects of emotional competence which are disrupted in mood disorders. Structural alterations of VMPFC have consistently been observed in adult major depression and are associated with depression severity, yet it is unknown whether young children with depression demonstrate similar abnormalities. We investigated cortical thickness differences in the VMPFC of children with a history of preschool-onset depression (PO-MDD). Methods Participants in a longitudinal study of PO-MDD underwent structural brain imaging between the ages of 7 to 12 years. Using local cortical distance metrics, cortical thickness of the VMPFC was compared in children with and without a history of PO-MDD. Results Children previously diagnosed with PO-MDD (n=34) had significantly thinner right VMPFC versus children without a history of PO-MDD [(n=95); F(1,126)=5.97, p=0.016)]. This effect was specific to children with a history of PO-MDD vs. other psychiatric conditions and was independent of comorbid anxiety or externalizing disorders. Decreases in right VMPFC thickness were predicted by preschool depressive symptoms independent of depressive symptoms in school age. Limitations Results are cross-sectional and cannot distinguish whether thinner right VMPFC represents a vulnerability marker of MDD, consequence of MDD, or marker of remitted MDD. Longitudinal imaging is needed to contextualize how this difference relates to normative VMPFC structural development. Conclusions Onset of depression at preschool age was associated with decreased cortical thickness of right VMPFC. This finding implicates the VMPFC in depression from very early stages of brain development. PMID:25881284

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

    PubMed Central

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

    2013-01-01

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

  13. Reward Sensitivity Enhances Ventrolateral Prefrontal Cortex Activation during Free Choice

    PubMed Central

    Cho, Catherine; Smith, David V.; Delgado, Mauricio R.

    2016-01-01

    Expressing one's preference via choice can be rewarding, particularly when decisions are voluntarily made as opposed to being forced. An open question is whether engaging in choices involving rewards recruits distinct neural systems as a function of sensitivity to reward. Reward sensitivity is a trait partly influenced by the mesolimbic dopamine system, which can impact an individual's neural and behavioral response to reward cues. Here, we investigated how reward sensitivity contributes to neural activity associated with free and forced choices. Participants underwent a simple decision-making task, which presented free- or forced-choice trials in the scanner. Each trial presented two cues (i.e., points or information) that led to monetary reward at the end of the task. In free-choice trials, participants were offered the opportunity to choose between different reward cues (e.g., points vs. information), whereas forced-choice trials forced individuals to choose within a given reward cue (e.g., information vs. information, or points vs. points). We found enhanced ventrolateral prefrontal cortex (VLPFC) activation during free choice compared to forced choice in individuals with high reward sensitivity scores. Next, using the VLPFC as a seed, we conducted a PPI analysis to identify brain regions that enhance connectivity with the VLPFC during free choice. Our PPI analyses on free vs. forced choice revealed increased VLPFC connectivity with the posterior cingulate and precentral gyrus in reward sensitive individuals. These findings suggest reward sensitivity may recruit attentional control processes during free choice potentially supporting goal-directed behavior and action selection. PMID:27917106

  14. The prefrontal cortex and the executive control of attention

    PubMed Central

    Rossi, Andrew F.; Pessoa, Luiz; Desimone, Robert

    2009-01-01

    We review two studies aimed at understanding the role of prefrontal cortex (PFC) in the control of attention. The first study examined which attentional functions are critically dependent on PFC by removing PFC unilaterally and transecting the forebrain commissures in two macaques. The monkeys fixated a central cue and discriminated the orientation of a colored target grating presented among colored distracter gratings in either the hemifield affected by the PFC lesion or the normal control hemifield. When the cue was held constant for many trials, task performance in the affected hemifield was nearly normal. However, performance was severely impaired when the cue was switched frequently across trials. The monkeys were unimpaired in a pop-out task with changing targets that did not require top-down attentional control. Thus, the PFC lesion resulted in selective impairment in the monkeys’ ability to switch top-down control. In the second study, we used fMRI to investigate the neural correlates of top-down control in humans performing tasks identical to those used in the monkey experiments. Several fronto-parietal and posterior visual areas showed enhanced activation when attention was switched, which was greater on color cueing (top-down) trials relative to pop-out trials. Taken together, our findings indicate that both frontal and parietal cortices are involved in generating top-down control signals for attentive switching, which may then be fed back to visual processing areas. The PFC in particular plays a critical role in the ability to switch attentional control on the basis of changing task demands. PMID:19030851

  15. Prefrontal cortex function in remitted major depressive disorder.

    PubMed

    Nixon, N L; Liddle, P F; Worwood, G; Liotti, M; Nixon, E

    2013-06-01

    Recent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence. Method Baseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patients versus controls and recurrence versus non-recurrence versus control groups. Analysis of patients (n = 20) versus controls (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence. Convergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.

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

    PubMed

    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.

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

    PubMed

    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.

  18. Interareal Spike-Train Correlations of Anterior Cingulate and Dorsal Prefrontal Cortex during Attention Shifts.

    PubMed

    Oemisch, Mariann; Westendorff, Stephanie; Everling, Stefan; Womelsdorf, Thilo

    2015-09-23

    The anterior cingulate cortex (ACC) and prefrontal cortex (PFC) are believed to coactivate during goal-directed behavior to identify, select, and monitor relevant sensory information. Here, we tested whether coactivation of neurons across macaque ACC and PFC would be evident at the level of pairwise neuronal correlations during stimulus selection in a spatial attention task. We found that firing correlations emerged shortly after an attention cue, were evident for 50-200 ms time windows, were strongest for neuron pairs in area 24 (ACC) and areas 8 and 9 (dorsal PFC), and were independent of overall firing rate modulations. For a subset of cell pairs from ACC and dorsal PFC, the observed functional spike-train connectivity carried information about the direction of the attention shift. Reliable firing correlations were evident across area boundaries for neurons with broad spike waveforms (putative excitatory neurons) as well as for pairs of putative excitatory neurons and neurons with narrow spike waveforms (putative interneurons). These findings reveal that stimulus selection is accompanied by slow time scale firing correlations across those ACC/PFC subfields implicated to control and monitor attention. This functional coupling was informative about which stimulus was selected and thus indexed possibly the exchange of task-relevant information. We speculate that interareal, transient firing correlations reflect the transient coordination of larger, reciprocally interacting brain networks at a characteristic 50-200 ms time scale. Significance statement: Our manuscript identifies interareal spike-train correlations between primate anterior cingulate and dorsal prefrontal cortex during a period where attentional stimulus selection is likely controlled by these very same circuits. Interareal correlations emerged during the covert attention shift to one of two peripheral stimuli, proceeded on a slow 50-200 ms time scale, and occurred between putative pyramidal and

  19. Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients

    PubMed Central

    Lim, Manyoel; Kim, June Sic; Kim, Dajung J.; Chung, Chun Kee

    2016-01-01

    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 (MEG) activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control (HC) 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 (S2) 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. PMID:27014041

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    PubMed Central

    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. PMID:25698942

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

    PubMed

    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.

  4. Suppression of Striatal Prediction Errors by the Prefrontal Cortex in Placebo Hypoalgesia.

    PubMed

    Schenk, Lieven A; Sprenger, Christian; Onat, Selim; Colloca, Luana; Büchel, Christian

    2017-10-04

    Classical learning theories predict extinction after the discontinuation of reinforcement through prediction errors. However, placebo hypoalgesia, although mediated by associative learning, has been shown to be resistant to extinction. We tested the hypothesis that this is mediated by the suppression of prediction error processing through the prefrontal cortex (PFC). We compared pain modulation through treatment cues (placebo hypoalgesia, treatment context) with pain modulation through stimulus intensity cues (stimulus context) during functional magnetic resonance imaging in 48 male and female healthy volunteers. During acquisition, our data show that expectations are correctly learned and that this is associated with prediction error signals in the ventral striatum (VS) in both contexts. However, in the nonreinforced test phase, pain modulation and expectations of pain relief persisted to a larger degree in the treatment context, indicating that the expectations were not correctly updated in the treatment context. Consistently, we observed significantly stronger neural prediction error signals in the VS in the stimulus context compared with the treatment context. A connectivity analysis revealed negative coupling between the anterior PFC and the VS in the treatment context, suggesting that the PFC can suppress the expression of prediction errors in the VS. Consistent with this, a participant's conceptual views and beliefs about treatments influenced the pain modulation only in the treatment context. Our results indicate that in placebo hypoalgesia contextual treatment information engages prefrontal conceptual processes, which can suppress prediction error processing in the VS and lead to reduced updating of treatment expectancies, resulting in less extinction of placebo hypoalgesia.SIGNIFICANCE STATEMENT In aversive and appetitive reinforcement learning, learned effects show extinction when reinforcement is discontinued. This is thought to be mediated by

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

    PubMed

    Chafee, Matthew V; Crowe, David A

    2017-10-11

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

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

    PubMed Central

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

    2015-01-01

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

  7. Amygdala and dorsomedial prefrontal cortex responses to appearance-based and behavior-based person impressions.

    PubMed

    Baron, Sean G; Gobbini, M I; Engell, Andrew D; Todorov, Alexander

    2011-10-01

    We explored the neural correlates of learning about people when the affective value of both facial appearance and behavioral information is manipulated. Participants were presented with faces that were either rated as high or low on trustworthiness. Subsequently, we paired these faces with positive, negative, or no behavioral information. Prior to forming face-behavior associations, a cluster in the right amygdala responded more strongly to untrustworthy than to trustworthy faces. During learning, a cluster in the dorsomedial prefrontal cortex (dmPFC) responded more strongly to faces paired with behaviors than faces not paired with behaviors. We also observed that the activity in the dmPFC was correlated with behavioral learning performance assessed after scanning. Interestingly, individual differences in the initial amygdala response to face trustworthiness prior to learning modulated the relationship between dmPFC activity and learning. This finding suggests that the activity of the amygdala can affect the interaction between dmPFC activity and learning.

  8. Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

    PubMed Central

    Gonzalez, María C.; Kramar, Cecilia P.; Tomaiuolo, Micol; Katche, Cynthia; Weisstaub, Noelia; Cammarota, Martín; Medina, Jorge H.

    2014-01-01

    Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus. PMID:25506318

  9. Amygdala and dorsomedial prefrontal cortex responses to appearance-based and behavior-based person impressions

    PubMed Central

    Gobbini, M. I.; Engell, Andrew D.; Todorov, Alexander

    2011-01-01

    We explored the neural correlates of learning about people when the affective value of both facial appearance and behavioral information is manipulated. Participants were presented with faces that were either rated as high or low on trustworthiness. Subsequently, we paired these faces with positive, negative, or no behavioral information. Prior to forming face–behavior associations, a cluster in the right amygdala responded more strongly to untrustworthy than to trustworthy faces. During learning, a cluster in the dorsomedial prefrontal cortex (dmPFC) responded more strongly to faces paired with behaviors than faces not paired with behaviors. We also observed that the activity in the dmPFC was correlated with behavioral learning performance assessed after scanning. Interestingly, individual differences in the initial amygdala response to face trustworthiness prior to learning modulated the relationship between dmPFC activity and learning. This finding suggests that the activity of the amygdala can affect the interaction between dmPFC activity and learning. PMID:21030482

  10. Transcranial direct current stimulation of the prefrontal cortex increases attention to visual target stimuli.

    PubMed

    Vierheilig, Nina; Mühlberger, Andreas; Polak, Thomas; Herrmann, Martin J

    2016-10-01

    Both functional imaging or EEG studies and studies including neurological patients found the dorsolateral prefrontal cortex (dLPFC) to be an important brain area for the processing of emotion and attention. The aim of the present study was to investigate whether emotion and attention can be modulated through bilateral transcranial direct current stimulation (tDCS) of the dLPFC. Therefore, we measured electroencephalographic occipital (early posterior negativity, EPN) and parietal ERPs (late positive potential, LPP) during an emotional picture viewing paradigm with an additional attentional instruction while applying bilateral anodal and cathodal tDC-stimulation to the left and right dLPFC. Beyond the well-known emotion and attention effects for both EPN and LPP, we found that left cathodal/right anodal tDCS leads to increased LPP amplitudes to target stimuli. In contrast to our hypothesis bilateral tDCS over the dLPFC did not influence emotional processing.

  11. Role of the medial prefrontal cortex in coping and resilience *

    PubMed Central

    Maier, Steven F.; Watkins, Linda R.

    2010-01-01

    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. PMID:20727864

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

    PubMed Central

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

    2009-01-01

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

  13. Tempering Proactive Cognitive Control by Transcranial Direct Current Stimulation of the Right (but Not the Left) Lateral Prefrontal Cortex.

    PubMed

    Gómez-Ariza, Carlos J; Martín, María C; Morales, Julia

    2017-01-01

    Behavioral and neuroimaging data support the distinction of two different modes of cognitive control: proactive, which involves the active and sustained maintenance of task-relevant information to bias behavior in accordance with internal goals; and reactive, which entails the detection and resolution of interference at the time it occurs. Both control modes may be flexibly deployed depending on a variety of conditions (i.e., age, brain alterations, motivational factors, prior experience). Critically, and in line with specific predictions derived from the dual mechanisms of control account (Braver, 2012), findings from neuroimaging studies indicate that the same lateral prefrontal regions (i.e., left dorsolateral cortex and right inferior frontal junction) may implement different control modes on the basis of temporal dynamics of activity, which would be modulated in response to external or internal conditions. In the present study, we aimed to explore whether transcraneal direct current stimulation over either the left dorsolateral prefrontal cortex or the right inferior frontal junction would differentially modulate performance on the AX-CPT, a well-validated task that provides sensitive and reliable behavioral indices of proactive/reactive control. The study comprised six conditions of real stimulation [3 (site: left dorsolateral, right dorsolateral and right inferior frontal junction) × 2 (polarity: anodal and cathodal)], and one sham condition. The reference electrode was always placed extracephalically. Performance on the AX-CPT was assessed through two blocks of trials. The first block took place while stimulation was being delivered, whereas the second block was administered after stimulation completion. The results indicate that both offline cathodal stimulation of the right dorsolateral prefrontal cortex and online anodal stimulation of the right inferior frontal junction led participants to be much less proactive, with such a dissociation suggesting

  14. Prior expectation modulates the interaction between sensory and prefrontal regions in the human brain.

    PubMed

    Rahnev, Dobromir; Lau, Hakwan; de Lange, Floris P

    2011-07-20

    How do expectations about the identity of a forthcoming visual stimulus influence the neural mechanisms of perceptual decision making in the human brain? Previous investigations into this issue have mostly involved changing the subjects' attentional focus or the behavioral relevance of certain targets but rarely manipulated subjects' prior expectation about the likely identity of the stimulus. Also, because perceptual decisions were often paired with specific motor responses, it has been difficult to dissociate neural activity that reflects perceptual decisions from motor preparatory activity. Here we designed a task in which we induced prior expectations about the direction of a moving-dot pattern and withheld the stimulus-response mapping until the subjects were prompted to respond. In line with current models of perceptual decision making, we found that subjects' performance was influenced by their expectation about upcoming motion direction. The integration of such information into the decision process was reflected by heightened activity in the dorsolateral prefrontal cortex. Activity in this area reflected the degree to which subjects adjusted their decisions based on the prior expectation cue. Furthermore, there was increased effective connectivity between sensory regions (motion-sensitive medial temporal area MT+) and dorsolateral prefrontal cortex when subjects had a prior expectation about the upcoming motion direction. Dynamic causal modeling suggested that stimulus expectation modulated both the feedforward and feedback connectivity between MT+ and prefrontal cortex. These results provide a mechanism of how prior expectations may affect perceptual decision making, namely by changing neural activity in, and sensory drive to, prefrontal areas.

  15. Inhibition processes are dissociable and lateralized in human prefrontal cortex.

    PubMed

    Cipolotti, Lisa; Spanò, Barbara; Healy, Colm; Tudor-Sfetea, Carina; Chan, Edgar; White, Mark; Biondo, Francesca; Duncan, John; Shallice, Tim; Bozzali, Marco

    2016-12-01

    The prefrontal cortex (PFC) is known to make fundamental contributions to executive functions. However, the precise nature of these contributions is incompletely understood. We focused on a specific executive function, inhibition, the ability to suppress a pre-potent response. Functional imaging and animal studies have studied inhibition. However, there are only few lesion studies, typically reporting discrepant findings. For the first time, we conducted cognitive and neuroimaging investigations on patients with focal unilateral PFC lesions across two widely used inhibitory tasks requiring a verbal response: The Hayling Part 2 and Stroop Colour-Word Tests. We systematically explored the relationship between inhibition, fluid intelligence and lesion location using voxel-based lesion symptom mapping (VLSM). We found that PFC patients were significantly impaired compared with healthy comparison group (HC) on both suppression measures of the Hayling and on the Stroop, even when performance on a fluid intelligence test was covaried. No significant relationship was found between patients' performance on each Hayling suppression measure and the Stroop, once fluid intelligence was partialled out, suggesting that the two tests may involve different kinds of inhibition. After accounting for fluid intelligence, we found a significant interaction between tests, Hayling or Stroop, and site, left or right, of PFC damage. This finding suggesting lateralized functional organization was complemented and extended by our VLSM results. We found that performance on both Hayling suppression measures significantly relied on the integrity of a similar and relatively circumscribed region within the right lateral PFC, in the right lateral superior and middle frontal gyri. In stark contrast, performance on the Stroop relies on the integrity of left lateral superior and middle frontal gyri. Thus, lesion location, right or left PFC, is critical in producing impairments on two inhibitory tasks

  16. Chronic infusions of GABA into the medial prefrontal cortex induce spatial alternation deficits in aged rats.

    PubMed

    Meneses, S; Galicia, O; Brailowsky, S

    1993-10-21

    It has been proposed that functions associated with the prefrontal cortex could change as a consequence of aging. Previous experiments in young rats have demonstrated that anatomical lesions or chronic GABA infusions into this area produce deficits in spatial delayed alternation tasks. The present study examines the effect of chronic (7 days) GABA or saline infusion into the prefrontal cortex on the performance of delayed alternation task in old rats (24 months). The results suggested that aged rats needed more sessions to acquire the delayed alternation task. GABA infusions into the prefrontal cortex produced deficits in spatial alternation tasks similar to those previously observed in young rats. Performance rapidly recovered after the infusion period. Histological analysis showed similar lesion size in both groups. The results suggest that aged prefrontal cortex and/or related areas participating in the acquisition of the delayed alternation task are more sensitive to aging processes. Furthermore, the prefrontal cortex is important for the retention of a previously learned spatial delayed alternation task. The structures involved in functional recovery from these deficits appear to be fully functional in aged rats.

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

    PubMed

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

    2017-03-03

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

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

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

  19. Role of the prefrontal cortex in attentional control over bistable vision.

    PubMed

    Windmann, Sabine; Wehrmann, Michaela; Calabrese, Pasquale; Güntürkün, Onur

    2006-03-01

    The primary source of top-down attentional control in object perception is the prefrontal cortex. This region is involved in the maintenance of goal-related information as well as in attentional selection and set shifting. Recent approaches have emphasized the role of top-down processes during elementary visual processes as exemplified in bistable vision where perception oscillates automatically between two mutually exclusive states. The prefrontal cortex might influence this process either by maintaining the dominant pattern while protecting it against the competing representation, or by facilitating perceptual switches between the two competing representations. To address this issue, we investigated reported perceptual reversals in patients with circumscribed lesions of the prefrontal cortex and healthy control participants in three experimental conditions: hold (maintaining the dominant view), speed (inducing as many perceptual switches as possible), and neutral (no intervention). Results indicated that although the patients showed normal switching rates in the neutral condition and were able to control perceptual switches in the hold condition as much as control subjects were, they were less able to facilitate reversals specifically in the speed condition. These results suggest that the prefrontal cortex is necessary to bias the selection of visual representations in accord with current goals, but is less essential for maintaining selected information active that is continuously available in the environment. As for attentional selection, the present results suggest that the prefrontal cortex initiates perceptual reversals by withdrawing top-down support from the dominant representation without (or prior to) boosting the suppressed view.

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

    PubMed

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

    2015-08-01

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

  1. [Reward information encoded by power of local field potentials in the primate prefrontal cortex and striatum].

    PubMed

    Chen, Yu-Ying; Pan, Xiao-Chuan; Wang, Ru-Bin; Sakagami, Masamichi

    2017-08-25

    Prefrontal cortex and striatum are two major areas in the brain. Some research reports suggest that both areas are involved in many advanced cognitive processes, such as learning and memory, reward processing, and behavioral decision. Single-unit recording experiments have found that neurons in the prefrontal cortex and striatum can represent reward information, but it remains elusive whether and how local field potentials (LFPs) in the two areas encode reward information. To investigate these issues, we recorded LFPs simultaneously in the prefrontal cortex and striatum of two monkeys by performing a reward prediction task (a large amount reward vs a small amount reward). Recorded LFP signals were transformed from the time domain to the time and frequency domain using the method of short-time Fourier transform (STFT). We calculated the power in each frequency and time, and examined whether they were different in the two reward conditions. The results showed that power of LFPs in both the prefrontal cortex and striatum distinguished one reward condition from the other one. And the power in small reward trials was greater than that in large reward trials. Furthermore, it was found that the LFPs better encoded reward information in the beta band (14-30 Hz) rather than other frequency bands. Our results suggest that the LFPs in the prefrontal cortex and striatum effectively represent reward information, which would help to further understand functional roles of LFPs in reward processing.

  2. Lost in transition: aging-related changes in executive control by the medial prefrontal cortex.

    PubMed

    Caetano, Marcelo S; Horst, Nicole K; Harenberg, Linda; Liu, Benjamine; Arnsten, Amy F T; Laubach, Mark

    2012-03-14

    Neural correlates of aging in the medial prefrontal cortex (mPFC) were studied using an operant delayed response task. The task used blocks of trials with memory-guided (delayed alternation) and visually-guided (stimulus-response) responding. Older rats (24 months) performed at a slow pace compared with younger rats (6 months). They wasted time engaged in nonessential behaviors (e.g., licking on spouts beyond the period of reward delivery) and were slow to respond at the end of the delay period. Aged mPFC neurons showed normal spatial processing. They differed from neurons in younger rats by having reduced modulations by imperative stimuli indicating reward availability and reduced activity associated with response latencies for reward collection. Older rats showed reduced sensitivity to imperative stimuli at three levels of neural activity: reduced fractions of neurons with changes in firing rate around the stimulus, reduced correlation over neurons at the time of the stimulus as measured with analysis of population activity, and reduced amplitudes of event-related fluctuations in intracortical field potentials at the time of the imperative stimulus. Our findings suggest that aging alters the encoding of time-sensitive information and impairs the ability of prefrontal networks to keep subjects "on task."

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

    PubMed

    Cheng, Gordon L F; Lee, Tatia M C

    2016-01-01

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

  4. Biological and social influences on cognitive control processes dependent on prefrontal cortex

    PubMed Central

    Diamond, Adele

    2014-01-01

    Cognitive control functions (“executive functions” [EFs] such as attentional control, self-regulation, working memory, and inhibition) that depend on prefrontal cortex (PFC) are critical for success in school and in life. Many children begin school lacking needed EF skills. Disturbances in EFs occur in many mental health disorders, such as ADHD and depression. This chapter addresses modulation of EFs by biology (genes and neurochemistry) and the environment (including school programs) with implications for clinical disorders and for education. Unusual properties of the prefrontal dopamine system contribute to PFC’s vulnerability to environmental and genetic variations that have little effect elsewhere. EFs depend on a late-maturing brain region (PFC), yet they can be improved even in infants and preschoolers, without specialists or fancy equipment. Research shows that activities often squeezed out of school curricula (play, physical education, and the arts) rather than detracting from academic achievement help improve EFs and enhance academic outcomes. Such practices may also head off problems before they lead to diagnoses of EF impairments, including ADHD. Many issues are not simply education issues or health issues; they are both. PMID:21489397

  5. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    PubMed

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  6. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    PubMed Central

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer’s patients. PMID:24339807

  7. Differential localization of protein phosphatase-1alpha, beta and gamma1 isoforms in primate prefrontal cortex.

    PubMed

    Bordelon, Jill R; Smith, Yoland; Nairn, Angus C; Colbran, Roger J; Greengard, Paul; Muly, E Chris

    2005-12-01

    Prefrontal cortical functioning depends on D1 family receptors and their complex signal transduction cascade, including protein phosphatase-1 (PP1). Three PP1 isoforms are prominent in the brain: PP1alpha, PP1beta and PP1gamma1. PP1 localization by a variety of scaffolding proteins is critical for dopamine-mediated modulation of glutamatergic neurotransmission. We have quantified the subcellular distribution of each isoform in primate prefrontal cortex using immunoelectron microscopy. All three are found in spines, dendrites, axon terminals, axons and glia. However, PP1alpha and PP1gamma1 labeling is enriched in spines, whereas PP1beta label is enriched in dendrites. Using post-embedding immunogold labeling, we further examined the distribution of PP1alpha and PP1gamma1 within spines. PP1gamma1 is highly and specifically concentrated in the postsynaptic density (PSD) of these spines, while PP1alpha is enriched in the PSD but also found subjacent to the PSD in moderate amounts. Thus, PP1 isoforms are heterogeneously distributed in the cortical neuropil and within spines. These results suggest that each PP1 isoform has access to a different set of substrates and, furthermore, they demonstrate that the composition of signal transduction proteins varies in different parts of the neuron and even in different regions of a dendritic spine in the primate PFC.

  8. Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments.

    PubMed

    George, Olivier; Mandyam, Chitra D; Wee, Sunmee; Koob, George F

    2008-09-01

    Humans with drug addiction exhibit compulsive drug-seeking associated with impairment of prefrontal cortex cognitive function. Whether prefrontal cortex dysfunction is a consequence of chronic drug exposure, or mediates the transition from drug use to drug dependence, is unknown. The current study investigates whether a history of escalated vs controlled cocaine intake is associated with specific working memory impairments, and long-lasting alterations of the dorsomedial prefrontal cortex and orbitofrontal cortex in rats. Working memory was assessed in rats with a history of extended (6 h per session) or limited (1 h per session) access to cocaine (0.5 mg/kg per injection), 3-17 days after the last self-administration session, using a delayed nonmatching-to-sample task. The density of neurons, oligodendrocytes, and astrocytes was quantified in the dorsomedial prefrontal cortex and orbitofrontal prefrontal cortex 2 months after the last self-administration session. Working memory impairments were observed after a history of chronic and escalated cocaine intake, but not after repeated limited access to cocaine. Moreover, working memory impairments were correlated with a decreased density of neurons and oligodendrocytes but not astrocytes in the dorsomedial prefrontal cortex, and with a decreased density of oligodendrocytes in the orbitofrontal cortex. Considering the role of the prefrontal cortex in goal-directed behavior, the prefrontal cortex dysfunctions observed here may exacerbate the loss of control associated with increased drug use and facilitate the progression to drug addiction.

  9. Alterations of attention and emotional processing following childhood-onset damage to the prefrontal cortex

    PubMed Central

    Sánchez-Navarro, Juan P.; Driscoll, David; Anderson, Steven W.; Tranel, Daniel; Bechara, Antoine; Buchanan, Tony W.

    2015-01-01

    The prefrontal cortex (PFC), especially the medial sector, plays a crucial role in emotional processing. Damage to this region results in impaired processing of emotional information, perhaps due to an inability to initiate and maintain attention toward emotional materials, a process that is normally automatic. Childhood onset damage to the PFC impairs emotional processing more than adult-onset PFC damage. The aim of this work was to study the involvement of the PFC in attention to emotional stimuli, and to explore how age at lesion onset affects this involvement. To address these issues, we studied both the emotional and attentional modulation of the startle reflex. Our sample was composed of 4 patients with childhood-onset PFC damage, 6 patients with adult-onset PFC damage, and 10 healthy comparison participants. Subjects viewed 54 affective pictures; acoustic startle probes were presented at 300 ms after picture onset in 18 pictures (as an index of attentional modulation) and at 3,800 ms after picture onset in 18 pictures (as an index of emotional modulation). Childhood-onset PFC patients did not show attentional or emotional modulation of the response, in contrast to adult-onset PFC damage and comparison participants. Early-onset damage to the PFC results, therefore, in more severe dysfunction in the processing of affective stimuli than adult-onset PFC damage, perhaps reflecting limited plasticity in the neural systems that support these processes. PMID:24377423

  10. Hypocretin and nicotine excite the same thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat.

    PubMed

    Lambe, Evelyn K; Olausson, Peter; Horst, Nicole K; Taylor, Jane R; Aghajanian, George K

    2005-05-25

    Thalamic projections to prefrontal cortex are important for executive aspects of attention. Using two-photon imaging in prefrontal brain slices, we show that nicotine and the wakefulness neuropeptide hypocretin (orexin) excite the same identified synapses of the thalamocortical arousal pathway within the prefrontal cortex. Although it is known that attention can be improved when nicotine is infused directly into the midlayer of the prefrontal cortex in the rat, the effects of hypocretin on attention are not known. The overlap in thalamocortical synapses excited by hypocretin and nicotine and the lack of direct postsynaptic effects prompted us to compare their effects on a sustained and divided attention task in the rat. Similar to nicotine, infusions of hypocretin-2 peptide into the prefrontal cortex significantly improved accuracy under high attentional demand without effects on other performance measures. We show for the first time that hypocretin can improve attentional processes relevant to executive functions of the prefrontal cortex.

  11. Dorsomedial prefrontal cortex mediates rapid evaluations predicting the outcome of romantic interactions

    PubMed Central

    Cooper, Jeffrey C.; Dunne, Simon; Furey, Teresa; O’Doherty, John P.

    2012-01-01

    Humans frequently make real-world decisions based on rapid evaluations of minimal information – for example, should we talk to an attractive stranger at a party? Little is known, however, about how the brain makes rapid evaluations with real and immediate social consequences. To address this question, we scanned participants with FMRI while they viewed photos of individuals that they subsequently met at real-life “speed-dating” events. Neural activity in two areas of dorsomedial prefrontal cortex, paracingulate cortex and rostromedial prefrontal cortex (RMPFC), was predictive of whether each individual would be ultimately pursued for a romantic relationship or rejected. Activity in these areas was attributable to two distinct components of romantic evaluation: either consensus judgments about physical beauty (paracingulate cortex) or individualized preferences based on a partner’s perceived personality (RMPFC). These data identify novel computational roles for these regions of the dorsomedial prefrontal cortex in even very rapid social evaluations. Even a first glance, then, can accurately predict romantic desire, but that glance involves a mix of physical and psychological judgments that depend on specific regions of dorsomedial prefrontal cortex. PMID:23136406

  12. NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.

    PubMed

    de Freitas, Renato Leonardo; Salgado-Rohner, Carlos José; Biagioni, Audrey Francisco; Medeiros, Priscila; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Coimbra, Norberto Cysne

    2014-06-01

    The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.

  13. Prefrontal cortex and manipulatory go left-go right differentiation to acoustic directional cues in dogs.

    PubMed

    Stepień, I; Stepień, L; Toeplitz, Z

    1975-01-01

    In 20 dogs the manipulatory go left – go right differentiation to acoustic directional cues was elaborated. All dogs received total prefrontal, or dorsolateral (total or partial) or medial (total or partial) cortical ablations. All total ablations markedly affected performance of the task, whereas the partial removals produced moderate or no impairment. Thus, both the dorsolateral and medial prefrontal cortex are involved in this type of differentiation.

  14. Sleep-Dependent Gene Expression in the Hippocampus and Prefrontal Cortex Following Long-Term Potentiation

    PubMed Central

    Romcy-Pereira, Rodrigo N.; Erraji-Benchekroun, Loubna; Smyrniotopoulos, Peggy; Ogawa, Sonoko; Mello, Claudio V.; Sibille, Etienne; Pavlides, Constantine

    2009-01-01

    The activity-dependent transcription factor zif268 is re-activated in sleep following hippocampal long-term potentiation (LTP). However, the activation of secondary genes, possibly involved in modifying local synaptic strengths and ultimately stabilizing memory traces during sleep, has not yet been studied. Here, we investigated changes in hippocampal and cortical gene expression at a time point subsequent to the previously reported initial zif268 re-activation during sleep. Rats underwent unilateral hippocampal LTP and were assigned to SLEEP or AWAKE groups. Eighty minutes after a long rapid-eye-movement sleep (REMS) episode (or an equivalent amount of time for awake group) animals had their hippocampi dissected and processed for gene microarray hybridization. Prefrontal and parietal cortices were also collected for qRT-PCR analysis. The microarray analysis identified 28 up-regulated genes in the hippocampus: 11 genes were enhanced in the LTPed hemisphere of sleep animals; 13 genes were enhanced after sleep, regardless of hemisphere; and 4 genes were enhanced in LTPed hemisphere, regardless of behavioral state. qRT-PCR analysis confirmed the upregulation of aif-1 and sc-65 during sleep. Moreover, we observed a down-regulation of the purinergic receptor, P2Y4R in the LTP hemisphere of awake animals and a trend for the protein kinase, CaMKI to be up-regulated in the LTP hemisphere of sleep animals. In the prefrontal cortex, we showed a significant LTP-dependent down-regulation of gluR1 and spinophilin specifically during sleep. Zif268 was downregulated in sleep regardless of the hemisphere. No changes in gene expression were observed in the parietal cortex. Our findings indicate that a set of synaptic plasticity-related genes have their expression modulated during sleep following LTP, which can reflect biochemical events associated with reshaping of synaptic connections in sleep following learning. PMID:19389414

  15. Dose-Dependent Changes in Auditory Sensory Gating in the Prefrontal Cortex of the Cynomolgus Monkey

    PubMed Central

    Huang, Hui; Ya, Jinrong; Wu, Zhe; Wen, Chunmei; Zheng, Suyue; Tian, Chaoyang; Ren, Hui; Carlson, Synnöve; Yu, Hualin; Chen, Feng; Wang, Jianhong

    2016-01-01

    Background Sensory gating, often described as the ability to filter out irrelevant information that is repeated in close temporal proximity, is essential for the selection, processing, and storage of more salient information. This study aimed to test the effect of sensory gating under anesthesia in the prefrontal cortex (PFC) of monkeys following injection of bromocriptine, haloperidol, and phencyclidine (PCP). Material/Methods We used an auditory evoked potential that can be elicited by sound to examine sensory gating during treatment with haloperidol, bromocriptine, and PCP in the PFC in the cynomolgus monkey. Scalp electrodes were located in the bilateral PFC and bilateral temporal, bilateral parietal, and occipital lobes. Administration of bromocriptine (0.313 mg/kg, 0.625 mg/kg, and 1.25 mg/kg), haloperidol (0.001 mg/kg, 0.01 mg/kg, and 0.05 mg/kg), and the N-methyl-D-aspartic acid receptor antagonist PCP (0.3 mg/kg) influenced sensory gating. Results We demonstrated the following: (1) Administration of mid-dose bromocriptine disrupted sensory gating (N100) in the right temporal lobe, while neither low-dose nor high-dose bromocriptine impaired gating. (2) Low-dose haloperidol impaired gating in the right prefrontal cortex. Mid-dose haloperidol disrupted sensory gating in left occipital lobe. High-dose haloperidol had no obvious effect on sensory gating. (3) Gating was impaired by PCP in the left parietal lobe. Conclusions Our studies showed that information processing was regulated by the dopaminergic system, which might play an important role in the PFC. The dopaminergic system influenced sensory gating in a dose- and region-dependent pattern, which might modulate the different stages that receive further processing due to novel information. PMID:27218151

  16. Glutamatergic contributions to nicotinic acetylcholine receptor agonist-evoked cholinergic transients in the prefrontal cortex.

    PubMed

    Parikh, Vinay; Man, Kingson; Decker, Michael W; Sarter, Martin

    2008-04-02

    Because modulation of cortical cholinergic neurotransmission has been hypothesized to represent a necessary mechanism mediating the beneficial cognitive effects of nicotine and nicotinic acetylcholine receptor (nAChR) subtype-selective agonists, we used choline-sensitive microelectrodes for the real-time measurement of ACh release in vivo, to characterize cholinergic transients evoked by nicotine and the alpha4beta2*-selective nAChR partial agonist 2-methyl-3-(2-(S)-pyrrolindinylmethoxy)pyridine dihydrochloride (ABT-089), a clinically effective cognition enhancer. In terms of cholinergic signal amplitudes, ABT-089 was significantly more potent than nicotine in evoking ACh cholinergic transients. Moreover, cholinergic signals evoked by ABT-089 were characterized by faster signal rise time and decay rate. The nAChR antagonist mecamylamine attenuated the cholinergic signals evoked by either compound. Cholinergic signals evoked by ABT-089 were more efficaciously attenuated by the relatively beta2*-selective nAChR antagonist dihydro-beta-erythroidine. The alpha7 antagonist methyllycaconitine did not affect choline signal amplitudes but partly attenuated the relatively slow decay rate of nicotine-evoked cholinergic signals. Furthermore, the AMPA receptor antagonist DNQX as well as the NMDA receptor antagonist APV more potently attenuated cholinergic signals evoked by ABT-089. Using glutamate-sensitive microelectrodes to measure glutamatergic transients, ABT-089 was more potent than nicotine in evoking glutamate release. Glutamatergic signals were highly sensitive to tetrodotoxin-induced blockade of voltage-regulated sodium channels. Together, the present evidence indicates that compared with nicotine, ABT-089 evokes more potent and sharper cholinergic transients in prefrontal cortex. Glutamatergic mechanisms necessarily mediate the cholinergic effects of nAChR agonists in the prefrontal cortex.

  17. Contributions of subregions of the prefrontal cortex to the theory of mind and decision making.

    PubMed

    Xi, Chunhua; Zhu, Youling; Niu, Chaoshi; Zhu, Chunyan; Lee, Tatia M C; Tian, Yanghua; Wang, Kai

    2011-08-10

    Recent works have suggested an association between the ventromedial prefrontal cortex (VMPC) and social cognition or decision making. The aim of this study is to investigate the theory of mind and decision making in patients with VMPC lesions and in those with dorsolateral prefrontal cortex (DLPC) lesions. Patients with VMPC lesions (n=16) and those with DLPC lesions (n=14) were compared with healthy controls (HC) on faux pas recognition and 2 decision-making tasks. Consistent with previous data, patients with VMPC lesions performed worse on the theory of mind and decision making. Patients with DLPC lesions showed impairments of the theory of mind but performed at control levels on the 2 decision-making tasks. The results supported the view that a separation of function of 2 distinct subregions of the prefrontal cortex is important to the theory of mind and decision making. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. [SOUND SIGNALS OF DANGER ACTIVATE THE NITRERGIC SYSTEM OF THE MEDIAL PREFRONTAL CORTEX].

    PubMed

    Sudorgina, P V; Saulskaya, N B

    2015-07-01

    In Sprague-Dawley rats by means of in vivo microdialysis, we have shown that presentation to rats-during conditioned fear expression of a sound conditioned stimulus previously paired with footshock (CS+) produces an increase in extracellular levels of citrulline (an NO co-product) in the medial prefrontal cortex. Presentation to the same rats of a different sound stimulus (not associated with footshock) (CS-) causes a very small increase in extracellular citrulline level. CS+ induced citrulline increase is prevented by infusions into the medial prefrontal cortex of Nomega-propyl-L-arginine (1 mM), a neuronal NO synthase inhibitor and it is not observed in control rats (same procedure, no footshock). These data indicate for the first time that sound signals of danger, but not safety signals activate nitrergic system of the medial prefrontal cortex.

  19. Magnetic Field Homogenization of the Human Prefrontal Cortex with a Set of Localized Electrical Coils

    PubMed Central

    Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Rothman, Douglas L.; de Graaf, Robin A.

    2011-01-01

    The prefrontal cortex is a common target brain structure in psychiatry and neuroscience due to its role in working memory and cognitive control. Large differences in magnetic susceptibility between the air-filled sinuses and the tissue/bone in the frontal part of the human head cause a strong and highly localized magnetic field focus in the prefrontal cortex. As a result, image distortion and signal dropout are observed in MR imaging. A set of external, electrical coils is presented that provides localized and high amplitude shim fields in the prefrontal cortex with minimum impact on the rest of the brain when combined with regular zero-to-second order spherical harmonics shimming. The experimental realization of the new shim method strongly minimized or even eliminated signal dropout in gradient-echo images acquired at settings typically used in functional magnetic resonance at 4 Tesla. PMID:19918909

  20. The role of the medial prefrontal cortex in human religious activity.

    PubMed

    Muramoto, Osamu

    2004-01-01

    Although religious practices are ubiquitous and universal throughout human history, their biological basis is little understood, particularly at the neural level. In this paper, I will first review the current understanding of the neural basis of human religious activity, and then present a hypothesis that the medial prefrontal cortex plays a vital role in the integrity of religious activity. In this hypothesis, optimal functions of the medial prefrontal cortex, such as error detection, compliance to social norms, self-reflection, and theory of mind, are a key prerequisite to the maintenance of integrated religious activity. Hyperreligiosity may result from the hyperfunction of the medial prefrontal cortex, including rigid legalism (excessive error detection), excessive concern over one's existence (excessive self-reflection), and delusional interpretation of God's mind (excess of theory of mind). Future research based on this hypothesis is proposed, and the potential implication of this hypothesis on our society is also discussed.

  1. Two principles of organization in the prefrontal cortex are cognitive hierarchy and degree of automaticity.

    PubMed

    Jeon, Hyeon-Ae; Friederici, Angela D

    2013-01-01

    The lateral prefrontal cortex is known to be organized by cognitive hierarchies following a posterior-to-anterior gradient. Here we test whether this model applies across different cognitive domains by varying levels of cognitive hierarchy in first language, second language and non-language domains. These domains vary in their degree of automaticity with first language being the most automatic. For second language/non-language a clear gradient pattern of activation depending on the level of hierarchy is observed in the prefrontal cortex with the highest level of hierarchy recruiting its most anterior region, whereas for first language the highest level of hierarchy recruits its most posterior region. Moreover, second language/non-language and first language differ in the structural connectivity of their underlying networks. The current data strongly suggest that functional segregation of the prefrontal cortex is determined by cognitive hierarchy and the degree of automaticity.

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

    PubMed

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

    2011-06-01

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

  3. Attenuation of dopamine-modulated prefrontal value signals underlies probabilistic reward learning deficits in old age.

    PubMed

    de Boer, Lieke; Axelsson, Jan; Riklund, Katrine; Nyberg, Lars; Dayan, Peter; Bäckman, Lars; Guitart-Masip, Marc

    2017-09-05

    Probabilistic reward learning is characterised by individual differences that become acute in aging. This may be due to age-related dopamine (DA) decline affecting neural processing in striatum, prefrontal cortex, or both. We examined this by administering a probabilistic reward learning task to younger and older adults, and combining computational modelling of behaviour, fMRI and PET measurements of DA D1 availability. We found that anticipatory value signals in ventromedial prefrontal cortex (vmPFC) were attenuated in older adults. The strength of this signal predicted performance beyond age and was modulated by D1 availability in nucleus accumbens. These results uncover that a value-anticipation mechanism in vmPFC declines in aging, and that this mechanism is associated with DA D1 receptor availability.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

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

  7. A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

    PubMed Central

    Wang, Huaixing; Stradtman, George G.; Wang, Xiao-Jing; Gao, Wen-Jun

    2008-01-01

    In the prefrontal cortex, NMDA receptors are important for normal prefrontal functions such as working memory, and their dysfunction plays a key role in the pathological processes of psychiatric disorders such as schizophrenia. Little is known, however, about the synaptic properties of NMDA receptors in the local circuits of recurrent excitation, a leading candidate mechanism underlying working memory. We investigated the NMDA receptor-mediated currents at monosynaptic connections between pairs of layer 5 pyramidal neurons. We found that NMDA receptor-mediated currents at prefrontal synapses in the adult, but not young, rats exhibit a twofold longer decay time-constant and temporally summate a train of stimuli more effectively, compared to those in the primary visual cortex. Experiments with pharmacological, immunocytochemical, and biochemical approaches further suggest that, in the adult animals, neurons express significantly more NR2B subunits in the prefrontal cortex than the visual cortex. The NR2B-rich synapses in the prefrontal circuitry may be critically implicated in online cognitive computations and plasticity in learning, as well as psychiatric disorders. PMID:18922773

  8. Action-value comparisons in the dorsolateral prefrontal cortex control choice between goal-directed actions

    PubMed Central

    Morris, Richard W.; Dezfouli, Amir; Griffiths, Kristi R.; Balleine, Bernard W.

    2014-01-01

    It is generally assumed that choice between different actions reflects the difference between their action values yet little direct evidence confirming this assumption has been reported. Here we assess whether the brain calculates the absolute difference between action values or their relative advantage, that is, the probability that one action is better than the other alternatives. We use a two-armed bandit task during functional magnetic resonance imaging and modelled responses to determine both the size of the difference between action values (D) and the probability that one action value is better (P). The results show haemodynamic signals corresponding to P in right dorsolateral prefrontal cortex (dlPFC) together with evidence that these signals modulate motor cortex activity in an action-specific manner. We find no significant activity related to D. These findings demonstrate that a distinct neuronal population mediates action-value comparisons, and reveals how these comparisons are implemented to mediate value-based decision-making. PMID:25055179

  9. Adolescent earthquake survivors' show increased prefrontal cortex activation to masked earthquake images as adults.

    PubMed

    Du, Xue; Wei, Dongtao; Ganzel, Barbara L; Kim, Pilyoung; Zhang, Qinglin; Qiu, Jiang

    2015-03-01

    The great Sichuan earthquake in China on May 12, 2008 was a traumatic event to many who live near the earthquake area. However, at present, there are few studies that explore the long-term impact of the adolescent trauma exposure on adults' brain function. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the brain activation evoked by masked trauma-related stimuli (earthquake versus neutral images) in 14 adults who lived near the epicenter of the great Sichuan earthquake when they were adolescents (trauma-exposed group) and 14 adults who lived farther from the epicenter of the earthquake when they were adolescents (control group). Compared with the control group, the trauma-exposed group showed significant elevation of activation in the right anterior cingulate cortex (ACC) and the medial prefrontal cortex (MPFC) in response to masked earthquake-related images. In the trauma-exposed group, the right ACC activation was negatively correlated with the frequency of symptoms of post-traumatic stress disorder (PTSD). These findings differ markedly from the long-term effects of trauma exposure in adults. This suggests that trauma exposure during adolescence may have a unique long-term impact on ACC/MPFC function, top-down modulation of trauma-related information, and subsequent symptoms of PTSD.

  10. Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory

    PubMed Central

    Brennan, Avis R.; Dolinsky, Beth; Vu, Mai-Anh T.; Stanley, Marion; Yeckel, Mark F.; Arnsten, Amy F.T.

    2008-01-01

    Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP3-PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP3 receptor (IP3R)-evoked calcium release results in SK channel-dependent hyperpolarization of prefrontal neurons. However, the effects of IP3R signaling on prefrontal function have not been investigated. The present findings demonstrate that blockade of IP3R or SK channels in the prefrontal cortex enhances WM performance in rats, suggesting that both arms of the PI cascade influence prefrontal cognitive function. PMID:18285467

  11. Reduced Global Functional Connectivity of the Medial Prefrontal Cortex in Major Depressive Disorder

    PubMed Central

    Murrough, James W.; Abdallah, Chadi G.; Anticevic, Alan; Collins, Katherine A.; Geha, Paul; Averill, Lynnette A.; Schwartz, Jaclyn; DeWilde, Kaitlin E.; Averill, Christopher; Yang, Genevieve Jia-wei; Wong, Edmund; Tang, Cheuk Y.; Krystal, John H.; Iosifescu, Dan V.; Charney, Dennis S.

    2016-01-01

    Background Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity. Methods A total of 82 subjects, including medication-free patients with major depression (n=57) and healthy volunteers (n=25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel’s time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation. Results Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges’ g = −1.48, p<0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = −0.47, p=0.0005). Conclusions Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. PMID:27144347

  12. Dissociable Roles of Ventromedial Prefrontal Cortex (vmPFC) and Rostral Anterior Cingulate Cortex (rACC) in Value Representation and Optimistic Bias

    PubMed Central

    Blair, Karina S.; Otero, Marcela; Teng, Cindy; Jacobs, Madeline; Odenheimer, Stephanie; Pine, Daniel S.; Blair, R. J. R.

    2013-01-01

    Optimistic bias (OB) is seen when individuals underestimate their probability of experiencing negative life events and overestimate their probability of experiencing positive life events. A reduced OB has been linked with increased depression symptoms . However, given the relevance of this information to mood and anxiety disorders, little is currently known regarding the neurobiology of OB. In the current study, we examine the neural basis of OB in healthy individuals (n=33) during probability estimation of future positive and negative events occurring to themselves relative to other, comparable individuals. In line with previous work, subjects showed significant OB; they considered themselves significantly more likely to experience future positive and significantly less likely to experience future negative events relative to comparable others. Positive, relative to negative events, un-modulated by subjects’ probability estimates, were associated with significantly greater activity within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Moreover, responses within both regions to positive events negatively related to the healthy subjects’ self reports of depression symptoms. However, there was no significant modulation of activity in either region by the subject’s OB, objectified as the level to which they thought the event was more likely [positive events] or less likely [negative events] to occur to them relative to comparable others. In contrast, activity within rostral anterior cingulate cortex (rACC) was positively modulated by OB for positive events and activity within anterior insula and dorsomedial prefrontal cortex (dmPFC) was negatively modulated by OB for negative events. However, there was no significant relationship between responsiveness within these regions and self reports of depression symptoms. The data are discussed with reference to current models of vmPFC, rACC and anterior insula functioning. PMID:23567883

  13. NORADRENERGIC, BUT NOT CHOLINERGIC, DEAFFERENTATION OF PREFRONTAL CORTEX IMPAIRS ATTENTIONAL SET-SHIFTING

    PubMed Central

    McGAUGHY, J.; ROSS, R. S.; EICHENBAUM, H.

    2008-01-01

    Both norepinephrine and acetylcholine have been shown to be critically involved in mediating attention but there remains debate about whether they serve similar or unique functions. Much of what is known about the role of these neurochemicals in cognition is based on manipulations done at the level of the cell body but these findings are difficult to reconcile with data regarding the unique contribution of cortical subregions, e.g. the dorsolateral prefrontal cortex, to attention. In the current study, we directly compared the effects of noradrenergic and cholinergic deafferentation of the rat medial prefrontal cortex, the homologue of primate dorsolateral prefrontal cortex, using an intradimensional/extradimensional attentional set shifting task, a task previously shown to be able to dissociate the function of the primate dorsolateral prefrontal cortex from orbitofrontal cortex. We found that noradrenergic, but not cholinergic, deafferentation produces specific impairments in the ability to shift attentional set. We also clarified the nature of the attentional deficits by assessing the ability of rats to disregard irrelevant stimuli. Noradrenergic lesions did not alter the ability of rats to ignore irrelevant stimuli, suggesting that the attentional deficit results from an overly focused attentional state that retards learning that a new stimulus dimension predicts reward. PMID:18355972

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

    PubMed

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

    2015-06-26

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

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

    PubMed Central

    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. What the rodent prefrontal cortex can teach us about attention-deficit/hyperactivity disorder: the critical role of early developmental events on prefrontal function.

    PubMed

    Sullivan, Ron M; Brake, Wayne G

    2003-11-30

    The present review surveys a broad range of findings on the functions of the rodent prefrontal cortex (PFC) in the context of the known pathophysiology of attention-deficit/hyperactivity disorder (ADHD). An overview of clinical findings concludes that dysfunction of the right PFC plays a critical role in ADHD and that a number of early developmental factors conspire to increase the risk of the disorder. Rodent studies are described which go far in explaining how the core processes which are deficient in ADHD are mediated by the PFC and that the mesocortical dopamine (DA) system plays a central role in modulating these functions. These studies also demonstrate a surprising degree of cerebral lateralization of prefrontal function in the rat. Importantly, the PFC is highly vulnerable to a wide variety of early developmental insults, which parallel the known risk factors for ADHD. It is suggested that the regulation of physiological and behavioral arousal is a fundamental role of the PFC, upon which many "higher" prefrontal functions are dependent or at least influenced. These right hemispheric arousal systems, of which the mesocortical DA system is a component, are greatly affected by early adverse events, both peri- and postnatally. Abnormal development, particularly of the right PFC and its DAergic afferents, is suggested to contribute directly to the core deficits of ADHD through dysregulation of the right frontostriatal system.

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

    PubMed Central

    Chan, Annie W.-Y.

    2013-01-01

    Recent neuroimaging studies in both human and non-human primates have identified face selective activation in the ventral lateral prefrontal cortex (VLPFC) even in the absence of working memory (WM) 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 VLPFC remain unclear. 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 VLPFC? What is the future direction for investigating visual representations in this cortex? This review focuses on the function, topography, and circuitry of the VLPFC to enhance our understanding of the evolution and development of this cortex. PMID:23847558

  18. Chronic Stress Alters Neural Activity in Medial Prefrontal Cortex During Retrieval of Extinction

    PubMed Central

    Wilber, Aaron A.; Walker, Adam G.; Southwood, Christopher J.; Farrell, Mollee R.; Lin, Grant L.; Rebec, George V.; Wellman, Cara L.

    2010-01-01

    Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). Rats then underwent fear conditioning and extinction while activity of neurons in infralimbic or prelimbic cortex was recorded. Percent freezing and neural activity were assessed during all phases of training. Chronic stress enhanced freezing during acquisition of conditioned fear, and altered both prelimbic and infralimbic activity during this phase. Stress did not alter initial extinction or conditioned stimulus (CS)-related activity during this phase. However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. In prelimbic cortex, unstressed rats showed decreased activity in response to CS presentation, whereas stressed rats showed no change. In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction. PMID:21044660

  19. Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women☆

    PubMed Central

    Chen, Yang-Kun; Xiao, Wei-Min; Wang, Defeng; Shi, Lin; Chu, Winnie CW; Mok, Vincent CT; Wong, Ka Sing; Ungvari, Gabor S; Tang, Wai Kwong

    2013-01-01

    This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged ≥ 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke. PMID:25206675

  20. Cellular resolution optical access to brain regions in fissures: imaging medial prefrontal cortex and grid cells in entorhinal cortex.

    PubMed

    Low, Ryan J; Gu, Yi; Tank, David W

    2014-12-30

    In vivo two-photon microscopy provides the foundation for an array of powerful techniques for optically measuring and perturbing neural circuits. However, challenging tissue properties and geometry have prevented high-resolution optical access to regions situated within deep fissures. These regions include the medial prefrontal and medial entorhinal cortex (mPFC and MEC), which are of broad scientific and clinical interest. Here, we present a method for in vivo, subcellular resolution optical access to the mPFC and MEC using microprisms inserted into the fissures. We chronically imaged the mPFC and MEC in mice running on a spherical treadmill, using two-photon laser-scanning microscopy and genetically encoded calcium indicators to measure network activity. In the MEC, we imaged grid cells, a widely studied cell type essential to memory and spatial information processing. These cells exhibited spatially modulated activity during navigation in a virtual reality environment. This method should be extendable to other brain regions situated within deep fissures, and opens up these regions for study at cellular resolution in behaving animals using a rapidly expanding palette of optical tools for perturbing and measuring network structure and function.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1996-02-01

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

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

    PubMed Central

    Ray, Rebecca; Zald, David H.

    2011-01-01

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

  4. The influence of dopaminergic system in medial prefrontal cortex on ketamine-induced amnesia in passive avoidance task in mice.

    PubMed

    Farahmandfar, Maryam; Bakhtazad, Atefeh; Akbarabadi, Ardeshir; Zarrindast, Mohammad-Reza

    2016-06-15

    Dopaminergic modulations of glutamate receptors are essential for the prefrontal cortical (PFC) behavioral and cognitive functions. In order to understand the effect of dopamine/glutamate interactions on learning and memory, we investigated the effects of intra medial prefrontal cortex (mPFC) injections of dopaminergic agents on ketamine-induced amnesia by using a one-trial passive avoidance task in mice. Pre-training administration of ketamine (5, 10 and 15mg/kg, i.p.) dose-dependently decreased the memory acquisition of a one-trial passive avoidance task. Pre-training intra-mPFC administration of SKF 38393, D1 receptor agonist and quinpirol D2 receptor agonist, alone did not affect memory acquisition. However, amnesia induced by pre-training ketamine (15mg/kg) significantly decreased by pretreatment of SKF 38393 (2 and 4µg/mouse) and quinpirol (0.3, 1 and 3µg/mouse). Pre-training administration of SCH 23390, D1 receptor antagonist (0.75 and 1μg/mouse, intra-mPFC), and sulpiride D2 receptor antagonist (3μg/mouse, intra-mPFC) impaired memory acquisition. In addition, co-pretreatment of different doses of SCH 23390 and sulpiride with lower dose of ketamine (5mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. It may be concluded that dopaminergic system of medial prefrontal cortex is involved in the ketamine-induced impairment of memory acquisition.

  5. Remote sensing of prefrontal cortex function with diffusive light

    NASA Astrophysics Data System (ADS)

    Zhao, Zhongyao; Wang, Xin C.; Chance, Britton

    2004-12-01

    A data bank on prefrontal imaging under stressful conditions including deceit, has been gathered over several years on National and International populations using a contact imager pad consisting of 16 detectors and 4 sources, validating the concept of imaging prefrontal responses to stress, not only following the response of the PFC to imaging stress but especially of precognitive activations. We designed a new portable and non-invasive optical detecting system for remote sensing of deceit at 1~2m distance. The signals of pre- and post-cognitive function in deceit can be detected with very high sensitivity for blood volume and blood oxygenation detection at depths sufficient for PFC imaging and sensitivities of sub-micromolar oxy-hemoglobin and blood concentration detection. Thus, remote imaging of the process of decision making seems possible and examples will be presented using both contact and flying spot remote sensing.

  6. Desynchronization and rebound of beta oscillations during conscious and unconscious local neuronal processing in the macaque lateral prefrontal cortex

    PubMed Central

    Panagiotaropoulos, Theofanis I.; Kapoor, Vishal; Logothetis, Nikos K.

    2013-01-01

    Accumulating evidence indicates that control mechanisms are not tightly bound to conscious perception since both conscious and unconscious information can trigger control processes, probably through the activation of higher-order association areas like the prefrontal cortex. Studying the modulation of control-related prefrontal signals in a microscopic, neuronal level during conscious and unconscious neuronal processing, and under control-free conditions could provide an elementary understanding of these interactions. Here we performed extracellular electrophysiological recordings in the macaque lateral prefrontal cortex (LPFC) during monocular physical alternation (PA) and binocular flash suppression (BFS) and studied the local scale relationship between beta (15–30 Hz) oscillations, a rhythmic signal believed to reflect the current sensory, motor, or cognitive state (status-quo), and conscious or unconscious neuronal processing. First, we show that beta oscillations are observed in the LPFC during resting state. Both PA and BFS had a strong impact on the power of this spontaneous rhythm with the modulation pattern of beta power being identical across these two conditions. Specifically, both perceptual dominance and suppression of local neuronal populations in BFS were accompanied by a transient beta desynchronization followed by beta activity rebound, a pattern also observed when perception occurred without any underlying visual competition in PA. These results indicate that under control-free conditions, at least one rhythmic signal known to reflect control processes in the LPFC (i.e., beta oscillations) is not obstructed by local neuronal, and accordingly perceptual, suppression, thus being independent from temporally co-existing conscious and unconscious local neuronal representations. Future studies could reveal the additive effects of motor or cognitive control demands on prefrontal beta oscillations during conscious and unconscious processing. PMID

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  9. Anxiety Evokes Hypofrontality and Disrupts Rule-Relevant Encoding by Dorsomedial Prefrontal Cortex Neurons

    PubMed Central

    Park, Junchol; Wood, Jesse; Bondi, Corina; Del Arco, Alberto

    2016-01-01

    Anxiety is a debilitating symptom of most psychiatric disorders, including major depression, post-traumatic stress disorder, schizophrenia, and addiction. A detrimental aspect of anxiety is disruption of prefrontal cortex (PFC)-mediated executive functions, such as flexible decision making. Here we sought to understand how anxiety modulates PFC neuronal encoding of flexible shifting between behavioral strategies. We used a clinically substantiated anxiogenic treatment to induce sustained anxiety in rats and recorded from dorsomedial PFC (dmPFC) and orbitofrontal cortex (OFC) neurons while they were freely moving in a home cage and while they performed a PFC-dependent task that required flexible switches between rules in two distinct perceptual dimensions. Anxiety elicited a sustained background “hypofrontality” in dmPFC and OFC by reducing the firing rate of spontaneously active neuronal subpopulations. During task performance, the impact of anxiety was subtle, but, consistent with human data, behavior was selectively impaired when previously correct conditions were presented as conflicting choices. This impairment was associated with reduced recruitment of dmPFC neurons that selectively represented task rules at the time of action. OFC rule representation was not affected by anxiety. These data indicate that a neural substrate of the decision-making deficits in anxiety is diminished dmPFC neuronal encoding of task rules during conflict-related actions. Given the translational relevance of the model used here, the data provide a neuronal encoding mechanism for how anxiety biases decision making when the choice involves overcoming a conflict. They also demonstrate that PFC encoding of actions, as opposed to cues or outcome, is especially vulnerable to anxiety. SIGNIFICANCE STATEMENT A debilitating aspect of anxiety is its impact on decision making and flexible control of behavior. These cognitive constructs depend on proper functioning of the prefrontal cortex

  10. Transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex alters P50 gating.

    PubMed

    Terada, Hidenori; Kurayama, Taichi; Nakazawa, Ken; Matsuzawa, Daisuke; Shimizu, Eiji

    2015-08-18

    Transcranial direct current stimulation (tDCS) has been reported to modify cortical function by inducing alterations in the underlying brain function. P50auditory evoked potentials, as assessed using a paired auditory stimulus (S1 and S2) paradigm, are thought to reflect a sensory gating process in which the functional involvement of the dorsolateral prefrontal cortex (DLPFC) is suggested. P50 sensory gating has also been reported to be associated with the pathogenesis of psychiatric diseases such as schizophrenia and anxiety-related disorders. Here we investigated whether the tDCS over the DLPFC could modulate the cortical function leading to alteration of the P50 sensory gating. P50 gating indices (the S2/S1 ratio and S1-S2 difference) were measured during the tDCS (current 1.0 mA, duration 15 min) over the DLPFC with different conditions (anodal, cathodal and sham). Ten male healthy volunteers were studied on separate days in a single blinded paradigm. We observed that the cathodaltDCS significantly altered the mean P50 gating indices compared to the other two conditions. Our results suggest that sensory gating could be modulated by cathodaltDCS on the left DLPFC but not by anodal/sham tDCS.

  11. Prefrontal cortex rTMS enhances action naming in progressive non-fluent aphasia.

    PubMed

    Cotelli, M; Manenti, R; Alberici, A; Brambilla, M; Cosseddu, M; Zanetti, O; Miozzo, A; Padovani, A; Miniussi, C; Borroni, B

    2012-11-01

    Progressive non-fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non-fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimer's disease. To investigate whether the modulation of DLPFC circuits by rTMS modifies naming performance in patients with PNFA. Ten patients with a diagnosis of PNFA were enrolled. High-frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group. A repeated-measure anova with stimulus site (sham, left and right rTMS) showed significant effects. Action-naming performances during stimulation of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported. Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  12. Emotion, Cognition, and Mental State Representation in Amygdala and Prefrontal Cortex

    PubMed Central

    Salzman, C. Daniel; Fusi, Stefano

    2011-01-01

    Neuroscientists have often described cognition and emotion as separable processes implemented by different regions of the brain, such as the amygdala for emotion and the prefrontal cortex for cognition. In this framework, functional interactions between the amygdala and prefrontal cortex mediate emotional influences on cognitive processes such as decision-making, as well as the cognitive regulation of emotion. However, neurons in these structures often have entangled representations, whereby single neurons encode multiple cognitive and emotional variables. Here we review studies using anatomical, lesion, and neurophysiological approaches to investigate the representation and utilization of cognitive and emotional parameters. We propose that these mental state parameters are inextricably linked and represented in dynamic neural networks composed of interconnected prefrontal and limbic brain structures. Future theoretical and experimental work is required to understand how these mental state representations form and how shifts between mental states occur, a critical feature of adaptive cognitive and emotional behavior. PMID:20331363

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Moriguchi, Yusuke; Hiraki, Kazuo

    2013-01-01

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

  15. [Is the prefrontal cortex the center of the universe?].

    PubMed

    Garcia-Molina, A; Ensenat, A

    2015-10-16

    Introduccion. Actualmente, cuando reflexionamos sobre cual es la estructura mas relevante del encefalo humano invariablemente pensamos en las regiones anteriores de la corteza cerebral, concretamente en la corteza prefrontal. Si bien este ha sido el dogma predominante a lo largo de mas de 150 años, investigadores de reconocido prestigio han cuestionado abiertamente tal supuesto. Desarrollo. A caballo entre los siglos XIX y XX, diversos investigadores consideraron que las regiones corticales posteriores son la sede neuroanatomica de las mas altas facultades intelectuales. Entre todos ellos destaco, por la elaboracion de sus propuestas e impacto en la comunidad cientifica, el neuroanatomista aleman Paul Emil Flechsig (1847-1929). Wilder Graves Penfield (1891-1976) fue otro detractor del dogma que considera la corteza prefrontal el sustrato anatomico de los procesos mentales mas complejos y sublimes del ser humano. A mediados del siglo XX, Penfield mantuvo la hipotesis de la existencia de lo que denomino el sistema de integracion centrencefalico, responsable del nivel mas elevado de integracion del sistema nervioso central. Conclusiones. Las concepciones corticocentricas otorgan el preciado cetro de 'estructura mas importante del encefalo' a la corteza prefrontal. Sin embargo, no han faltado propuestas alternativas que, con mayor o menor exito, han intentado arrebatarselo en favor de otras estructuras encefalicas.

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

    ERIC Educational Resources Information Center

    Gilbert, Sam J.; Burgess, Paul W.

    2008-01-01

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

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

    ERIC Educational Resources Information Center

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

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

    ERIC Educational Resources Information Center

    Gilbert, Sam J.; Burgess, Paul W.

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  2. Neuronal activity in the primate dorsomedial prefrontal cortex contributes to strategic selection of response tactics

    PubMed Central

    Matsuzaka, Yoshiya; Akiyama, Tetsuya; Tanji, Jun; Mushiake, Hajime

    2012-01-01

    The functional roles of the primate posterior medial prefrontal cortex have remained largely unknown. Here, we show that this region participates in the regulation of actions in the presence of multiple response tactics. Monkeys performed a forelimb task in which a visual cue required prompt decision of reaching to a left or a right target. The location of the cue was either ipsilateral (concordant) or contralateral (discordant) to the target. As a result of extensive training, the reaction times for the concordant and discordant trials were indistinguishable, indicating that the monkeys developed tactics to overcome the cue-response conflict. Prefrontal neurons exhibited prominent activity when the concordant and discordant trials were randomly presented, requiring rapid selection of a response tactic (reach toward or away from the cue). The following findings indicate that these neurons are involved in the selection of tactics, rather than the selection of action or monitoring of response conflict: (i) The response period activity of neurons in this region disappeared when the monkeys performed the task under the behavioral condition that required a single tactic alone, whereas the action varied across trials. (ii) The neuronal activity was found in the dorsomedial prefrontal cortex but not in the anterior cingulate cortex that has been implicated for the response conflict monitoring. These results suggest that the medial prefrontal cortex participates in the selection of a response tactic that determines an appropriate action. Furthermore, the observation of dynamic, task-dependent neuronal activity necessitates reconsideration of the conventional concept of cortical motor representation. PMID:22371582

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Peters, Gregory J.; David, Christopher N.; Marcus, Madison D.; Smith, David M.

    2013-01-01

    The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC…

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

    ERIC Educational Resources Information Center

    Poletti, Michele; Bonuccelli, Ubaldo

    2012-01-01

    A recent paper (Zald & Andreotti, 2010) reviewed neuropsychological tasks that assess the function of the orbital and ventromedial portions of the prefrontal cortex (OMPFC). Neuropathological studies have shown that the function of the OMPFC should be preserved in the early stages of Parkinson's disease (PD) but becomes affected in the advanced…

  6. When "Happy" Means "Sad": Neuropsychological Evidence for the Right Prefrontal Cortex Contribution to Executive Semantic Processing

    ERIC Educational Resources Information Center

    Samson, Dana; Connolly, Catherine; Humphreys, Glyn W.

    2007-01-01

    The contribution of the left inferior prefrontal cortex in semantic processing has been widely investigated in the last decade. Converging evidence from functional imaging studies shows that this region is involved in the "executive" or "controlled" aspects of semantic processing. In this study, we report a single case study of a patient, PW, with…

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

    ERIC Educational Resources Information Center

    Peters, Gregory J.; David, Christopher N.; Marcus, Madison D.; Smith, David M.

    2013-01-01

    The prefrontal cortex (PFC) is known to be critically involved in strategy switching, attentional set shifting, and inhibition of prepotent responses. A central feature of this kind of behavioral flexibility is the ability to resolve conflicting response tendencies, suggesting a general role of the PFC in resolving interference. If so, the PFC…

  8. The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories

    PubMed Central

    Jeye, Brittany M.; Karanian, Jessica M.; Slotnick, Scott D.

    2017-01-01

    False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC) and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI) study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the “left” or “right” visual field followed by an “unsure”–“sure”–“very sure” confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right–“left”–“very sure” responses) from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories. PMID:28124986

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

    ERIC Educational Resources Information Center

    Poletti, Michele; Bonuccelli, Ubaldo

    2012-01-01

    A recent paper (Zald & Andreotti, 2010) reviewed neuropsychological tasks that assess the function of the orbital and ventromedial portions of the prefrontal cortex (OMPFC). Neuropathological studies have shown that the function of the OMPFC should be preserved in the early stages of Parkinson's disease (PD) but becomes affected in the advanced…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

  14. The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories.

    PubMed

    Jeye, Brittany M; Karanian, Jessica M; Slotnick, Scott D

    2017-01-23

    False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC) and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI) study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the "left" or "right" visual field followed by an "unsure"-"sure"-"very sure" confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right-"left"-"very sure" responses) from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories.

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

    ERIC Educational Resources Information Center

    Lee, Inah; Shin, Ji Yun

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

    2012-01-01

    Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Tronel, Sophie; Feenstra, Matthijs G. P.; Sara, Susan J.

    2004-01-01

    These experiments investigated the role of the noradrenergic system in the late stage of memory consolidation and in particular its action at beta receptors in the prelimbic region (PL) of the prefrontal cortex in the hours after training. Rats were trained in a rapidly acquired, appetitively motivated foraging task based on olfactory…

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

    Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

    2012-01-01

    Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

  3. Distinct roles for lateral and medial anterior prefrontal cortex in contextual recollection.

    PubMed

    Simons, Jon S; Gilbert, Sam J; Owen, Adrian M; Fletcher, Paul C; Burgess, Paul W

    2005-07-01

    A key feature of human recollection is the ability to remember details of the context in which events were experienced, as well as details of the events themselves. Previous studies have implicated a number of regions of prefrontal cortex in contextual recollection, but the role of anterior prefrontal cortex has so far resisted detailed characterization. We used event-related functional MRI (fMRI) to contrast recollection of two forms of contextual information: 1) decisions one had previously made about stimuli (task memory) and 2) which of two temporally distinct lists those stimuli had been presented in (list memory). In addition, a retrieval cue manipulation permitted evaluation of the stage of the retrieval process in which the activated regions might be involved. The results indicated that anterior prefrontal cortex responded significantly more during recollection of task than list context details. Furthermore, activation profiles for lateral and medial aspects of anterior prefrontal cortex suggested differing roles in recollection. Lateral regions seem to be more involved in the early retrieval specification stages of recollection, with medial regions contributing to later stages (e.g., monitoring and verification).

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

    ERIC Educational Resources Information Center

    Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

    2010-01-01

    Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Baran, Sarah E.; Armstrong, Charles E.; Niren, Danielle C.; Conrad, Cheryl D.

    2010-01-01

    Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague-Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h…

  8. The impact of age on prefrontal cortex integrity during spatial working memory retrieval.

    PubMed

    Toepper, Max; Markowitsch, Hans J; Gebhardt, Helge; Beblo, Thomas; Bauer, Eva; Woermann, Friedrich G; Driessen, Martin; Sammer, Gebhard

    2014-07-01

    Healthy aging is accompanied by a decline in spatial working memory that is related to functional cerebral changes within the spatial working memory network. In the last decade, important findings were presented concerning the location (e.g., prefrontal), kind (e.g., 'underactivation,' 'overactivation'), and meaning (e.g., functional deficits, compensation) of these changes. Less is known about how functional connections between specific brain regions are affected by age and how these changes are related to behavioral performance. To address these issues, we used functional magnetic resonance imaging to examine retrieval-related brain activation and functional connectivity in 18 younger individuals and 18 older individuals. We assessed working memory with a modified version of the Corsi Block-Tapping test, which requires the storage and reproduction of spatial target sequences. Analyses of group differences in brain activation and functional connectivity included comparisons between younger individuals, older individuals, older high-performers, and older low-performers. In addition, we conducted a functional connectivity analysis by using a seed region approach. In comparison to younger individuals, older individuals showed lower right-hemispheric dorsolateral prefrontal activation and lower functional connectivity between the right dorsolateral prefrontal cortex and the bilateral orbitofrontal cortex. Older high-performers showed higher right dorsolateral and anterior prefrontal cortex activation than older low-performers, as well as higher functional connectivity between these brain regions. The present results suggest age-related reductions of prefrontal activation during spatial working memory retrieval. Moreover, task-related functional connectivity appears to be lower in older adults. Performance accuracy in older adults is associated with right dorsolateral and anterior prefrontal cortex activation, and with the functional connection between these regions.

  9. Human orbital and anterior medial prefrontal cortex: Intrinsic connectivity parcellation and functional organization.

    PubMed

    Samara, Zoe; Evers, Elisabeth A T; Goulas, Alexandros; Uylings, Harry B M; Rajkowska, Grazyna; Ramaekers, Johannes G; Stiers, Peter

    2017-03-02

    The orbital and medial prefrontal cortex (OMPFC) has been implicated in decision-making, reward and emotion processing, and psychopathology, such as depression and obsessive-compulsive disorder. Human and monkey anatomical studies indicate the presence of various cortical subdivisions and suggest that these are organized in two extended networks, a medial and an orbital one. Attempts have been made to replicate these neuroanatomical findings in vivo using MRI techniques for imaging connectivity. These revealed several consistencies, but also many inconsistencies between reported results. Here, we use fMRI resting-state functional connectivity (FC) and data-driven modularity optimization to parcellate the OMPFC to investigate replicability of in vivo parcellation more systematically. By collecting two resting-state data sets per participant, we were able to quantify the reliability of the observed modules and their boundaries. Results show that there was significantly more than chance overlap in modules and their boundaries at the level of individual data sets. Moreover, some of these consistent boundaries significantly co-localized across participants. Hierarchical clustering showed that the whole-brain FC profiles of the OMPFC subregions separate them in two networks, a medial and orbital one, which overlap with the organization proposed by Barbas and Pandya (J Comp Neurol 286:353-375, 1989) and Ongür and Price (Cereb Cortex 10:206-219, 2000). We conclude that in vivo resting-state FC can delineate reliable and neuroanatomically plausible subdivisions that agree with established cytoarchitectonic trends and connectivity patterns, while other subdivisions do not show the same consistency across data sets and studies.

  10. Altered Markers of Tonic Inhibition in the Dorsolateral Prefrontal Cortex of Subjects With Schizophrenia

    PubMed Central

    Maldonado-Avilés, Jaime G.; Curley, Allison A.; Hashimoto, Takanori; Morrow, A. Leslie; Ramsey, Amy J.; O’Donnell, Patricio; Volk, David W.; Lewis, David A.

    2010-01-01

    Objective Cognitive impairments in schizophrenia are associated with lower expression of markers of γ-aminobutyric acid (GABA) synthesis in the prefrontal cortex. The effects of GABA are mediated by GABAA receptors that mediate either phasic or tonic inhibition. The authors assessed the expression of GABAA receptor α4 and δ subunits, which coassemble to form receptors mediating tonic inhibition, in schizophrenia. Method The authors used in situ hybridization to quantify expression patterns of GABAA receptor α4 and δ subunits in pre-frontal cortex from 23 matched pairs of schizophrenia and comparison subjects. Results Levels of δ mRNA were significantly lower in schizophrenia subjects regardless of medication use, whereas α4 mRNA levels were lower only in subjects with schizophrenia receiving certain medications at the time of death. To understand the nature of this unexpected dissociation between α 4 and δ subunit expression in schizophrenia, the authors used similar methods to quantify α4 and δ mRNA levels in multiple animal models. During postnatal development of monkey prefrontal cortex, levels of α4 mRNA decreased, whereas δ mRNA levels increased. In addition, δ mRNA levels, but not α4 mRNA levels, were lower in the medial frontal cortex of mice with a genetic deletion of the GABAA receptor α1 subunit, and neither δ nor α4 mRNA levels were altered in rodent models of altered excitatory neurotransmission. Conclusions Since GABAA receptor α1 subunits also have lower mRNA levels in schizophrenia, show increased expression with age in monkey prefrontal cortex, and can coassemble with δ subunits to form functional GABAA receptors, lower δ mRNA levels in schizophrenia might reflect a reduced number of α1βxδ GABAA receptors that could contribute to deficient tonic inhibition and prefrontal cortical dysfunction in schizophrenia. PMID:19289452

  11. Localization of DARPP-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex

    PubMed Central

    Glausier, Jill R.; Maddox, Marcelia; Hemmings, Hugh C.; Nairn, Angus C.; Greengard, Paul; Muly, E. Chris

    2010-01-01

    The actions of dopamine D1 family receptors (D1R) depend upon a signal transduction cascade that modulates the phosphorylation state of important effector proteins, such as glutamate receptors and ion channels. This is accomplished both through activation of protein kinase A (PKA) and the inhibition of protein phosphatase-1 (PP1). Inhibition of PP1 occurs through PKA-mediated phosphorylation of DARPP-32 or the related protein inhibitor-1 (I-1), and the availability of DARPP-32 is essential to the functional outcome of D1R activation in the basal ganglia. While D1R activation is critical for prefrontal cortex (PFC) function, especially working memory, the functional role played by DARPP-32 or I-1 is less clear. In order to examine this more thoroughly, we have utilized immunoelectron microscopy to quantitatively determine the localization of DARPP-32 and I-1 in the neuropil of the rhesus monkey PFC. Both were distributed widely in the different components of the neuropil, but were enriched in dendritic shafts. I-1 label was more frequently identified in axon terminals than was DARPP-32, and DARPP-32 label was more frequently identified in glia than was I-1. We also quantified the extent to which these proteins were found in dendritic spines. DARPP-32 and I-1 were present in small subpopulations of dendritic spines, (4.4 and 7.7% and respectively), which were substantially smaller than observed for D1R in our previous studies (20%). Double-label experiments did not find evidence for colocalization of D1R and DARPP-32 or I-1 in spines or terminals. Thus, at the least, not all prefrontal spines which contain D1R also contain I-1 or DARPP-32, suggesting important differences in D1R signaling in the PFC compared to the striatum. PMID:20156529

  12. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice.

    PubMed

    Cui, Yihui; Jin, Jing; Zhang, Xuliang; Xu, Hao; Yang, Liguo; Du, Dan; Zeng, Qingwen; Tsien, Joe Z; Yu, Huiting; Cao, Xiaohua

    2011-01-01

    Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory.

  13. Orbital and medial prefrontal cortex and psychostimulant abuse: studies in animal models.

    PubMed

    Porrino, L J; Lyons, D

    2000-03-01

    One approach to pursuing questions about the neural substrates that support substance abuse-related behaviors involves the use of animal models. Carefully controlled animal experiments can be conducted without the confounds commonly found in studies of human addicts, such as polydrug abuse, variable drug history and premorbid psychiatric conditions. The present paper considers the orbitofrontal and related limbic prefrontal cortex in the context of such models of substance abuse. First, the importance of recognizing the heterogeneous structural and functional nature of orbitofrontal cortex in both rodents and primates is addressed, and the results of studies involving the prefrontal cortex in substance abuse-related behaviors are considered in light of this diversity. Second, data from metabolic mapping studies are described that indicate that the pattern of functional activity within medial and orbitofrontal cortex shifts as the duration of exposure to drugs such as cocaine is extended. These functional differences, in turn, may reflect progressive phases of the addictive process. In order to understand the neurobiological consequences of long-term drug use, it will be important to establish the differing roles played by distinct anatomical territories within orbital and medial prefrontal cortex during the course of chronic substance abuse.

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

    PubMed

    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.

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

    PubMed

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

    2014-03-27

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

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

    PubMed

    Yaoi, Ken; Osaka, Naoyuki; Osaka, Mariko

    2009-01-01

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

  17. Development of thalamocortical connections between the mediodorsal thalamus and the prefrontal cortex and its implication in cognition

    PubMed Central

    Ferguson, Brielle R.; Gao, Wen-Jun

    2015-01-01

    The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the prefrontal cortex (PFC), and is thought to be highly implicated in modulation of cognitive performance. Additionally, it undergoes highly conserved developmental stages, which, when dysregulated, can have detrimental consequences. Embryonically, the MD experiences a tremendous surge in neurogenesis and differentiation, and disruption of this process may underlie the pathology in certain neurodevelopmental disorders. However, during the postnatal period, a vast amount of cell loss in the MD occurs. These together may represent an extended critical period for postnatal development, in which disturbances in the normal growth or reduction of the MD afferents to the PFC, can result in PFC-dependent cognitive, affective, or psychotic abnormalities. In this review, we explore the current knowledge supporting this hypothesis of a protracted critical period, and propose how developmental changes in the MD contribute to successful prefrontal cortical development and function. Specifically, we elaborate on the unique properties of MD-PFC connections compared with other thalamocortical afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic transmission in the local prefrontal circuitry, and speculate on what occurs during postnatal development, particularly within the early neonatal stage, as well as juvenile and adolescent periods. Finally, we discuss the questions that remain and propose future experiments in order to provide perspective and novel insights into the cause of neuropsychiatric disorders associated with MD-PFC development. PMID:25620923

  18. Specific EEG sleep pattern in the prefrontal cortex in primary insomnia.

    PubMed

    Perrier, Joy; Clochon, Patrice; Bertran, Françoise; Couque, Colette; Bulla, Jan; Denise, Pierre; Bocca, Marie-Laure

    2015-01-01

    To assess the specific prefrontal activity in comparison to those in the other main cortical areas in primary insomnia patients and in good sleepers. Fourteen primary insomnia patients and 11 good sleepers were included in the analysis. Participants completed one night of polysomnography in the sleep lab. Power spectra were calculated during the NREM (Non-rapid eyes movements) and the REM (Rapid eyes movements) sleep periods at prefrontal, occipital, temporal and central electrode positions. During the NREM sleep, the power spectra did not differ between groups in the prefrontal cortex; while primary insomnia patients exhibited a higher beta power spectrum and a lower delta power spectrum compared to good sleepers in other areas. During the REM sleep, the beta1 power spectrum was lower in the prefrontal cortex in primary insomnia patients compared to good sleepers; while no significant difference between groups was obtained for the other areas. The present study shows a specific prefrontal sleep pattern during the whole sleep period. In addition, we suggest that primary insomnia patients displayed a dysfunction in the reactivation of the limbic system during the REM sleep and we give additional arguments in favor of a sleep-protection mechanism displayed by primary insomnia patients.

  19. Impairment in Delayed Non-Matching to Sample Following Lesions of Dorsal Prefrontal Cortex

    PubMed Central

    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 lesions in this study included dorsolateral and dorsomedial aspects of the PFC. In a previous report, we published evidence of an impairment on the CSST as a consequence of DPFC lesions (Moore et al, 2009). Here we report that monkeys with lesions of the DPFC were also markedly impaired relative to controls on both the acquisition (rule learning) and performance (recognition memory) conditions of trial-unique DNMS. The presence and extent of the deficits that we observed were of some surprise and support the possibility that the dorsal prefrontal cortex plays a more direct role in learning and recognition memory than had been previously thought. PMID:23088539

  20. Reduced anterior prefrontal cortex activation in young binge drinkers during a visual working memory task.

    PubMed

    Crego, Alberto; Rodriguez-Holguín, Socorro; Parada, María; Mota, Nayara; Corral, Montserrat; Cadaveira, Fernando

    2010-06-01

    Working memory (WM) is a major cognitive function that is altered by chronic alcohol consumption. This impairment has been linked to alterations in the hippocampus and prefrontal cortex (PFC). Animal and human studies have shown that the adolescent brain is more sensitive to the neurotoxic effects of alcohol than the adult brain, particularly those structures that mature late on in development, such as the hippocampus and prefrontal brain. The aim of the present study was to assess visual working memory and its neural correlates in young university students who partake in intermittent consumption of large amounts of alcohol (binge drinkers). A sample of 42 binge drinkers and 53 corresponding control subjects performed an identical pairs continuous performance task (IP-CPT) in a combined event-related potential (ERP) and exact low-resolution brain electromagnetic tomography (eLORETA) study. The results revealed that, despite adequate performance, binge drinkers showed a smaller late positive component (LPC) associated with hypoactivation of the right anterior prefrontal cortex (aPFC) for matching stimuli, in comparison with control subjects. These findings may reveal binge drinking-related functional alteration in recognition working memory processes and suggest that impaired prefrontal cortex function may occur at an early age in binge drinkers.

  1. Impairment in delayed nonmatching to sample following lesions of dorsal prefrontal cortex.

    PubMed

    Moore, Tara L; Schettler, Stephen P; Killiany, Ronald J; Rosene, Douglas L; Moss, Mark B

    2012-12-01

    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 Nonmatching to Sample (DNMS) task, a benchmark test of rule learning and recognition memory. The DPFC lesions in this study included dorsolateral and dorsomedial aspects of the PFC. In a previous report, we published evidence of an impairment on the CSST as a consequence of DPFC lesions (Moore, Schettler, Killiany, Rosene, & Moss, 2009). Here we report that monkeys with lesions of the DPFC were also markedly impaired relative to controls on both the acquisition (rule learning) and performance (recognition memory) conditions of trial-unique DNMS. The presence and extent of the deficits that we observed were of some surprise and support the possibility that the dorsal prefrontal cortex plays a more direct role in learning and recognition memory than had been previously thought.

  2. Anterior prefrontal cortex contributes to action selection through tracking of recent reward trends

    PubMed Central

    Kovach, Christopher K.; Daw, Nathaniel; Rudrauf, David; Tranel, Daniel; O’Doherty, John P.; Adolphs, Ralph

    2012-01-01

    The functions of prefrontal cortex remain enigmatic, especially so for its anterior sectors, putatively ranging from planning to self-initiated behavior, social cognition, task-switching and memory. A predominant current theory regarding the most anterior sector, frontopolar cortex (FPC), is that it is involved in exploring alternate courses of action, but the detailed causal mechanisms remain unknown. Here we investigated this issue using the lesion method together with a novel model-based analysis. Eight patients with anterior prefrontal brain lesions including the FPC performed a 4-armed bandit task known from neuroimaging studies to activate FPC. Model-based analyses of learning demonstrated a selective deficit in the ability to extrapolate the most recent trend, despite an intact general ability to learn from past rewards. Whereas both brain-damaged and healthy controls used comparisons between the two most recent choice outcomes to infer trends that influenced their decision about the next choice, the group with anterior prefrontal lesions showed a complete absence of this component and instead based their choice entirely on the cumulative reward history. Given that the FPC is thought to be the most evolutionarily recent expansion of primate prefrontal cortex, we suggest that its function may reflect uniquely human adaptations to select and update models of reward contingency in dynamic environments. PMID:22723683

  3. Infralimbic Prefrontal Cortex is Responsible for Inhibiting Cocaine Seeking in Extinguished Rats

    PubMed Central

    Peters, Jamie; LaLumiere, Ryan T.; Kalivas, Peter W.

    2008-01-01

    The rat prelimbic prefrontal cortex and nucleus accumbens core are critical for initiating cocaine seeking. In contrast, the neural circuitry responsible for inhibiting cocaine seeking during extinction is unknown. The present findings using inhibition of selected brain nuclei with GABA agonists show that the suppression of cocaine seeking produced by prior extinction training required activity in the rat infralimbic cortex. Conversely, the reinstatement of drug seeking by a cocaine injection in extinguished animals was suppressed by increasing neuronal activity in infralimbic cortex with the glutamate agonist AMPA. The cocaine seeking induced by inactivating infralimbic cortex resembled other forms of reinstated drug seeking by depending on activity in prelimbic cortex and the basolateral amygdala. A primary efferent projection from the infralimbic cortex is to the nucleus accumbens shell. Akin to infralimbic cortex, inhibition of the accumbens shell induced cocaine seeking in extinguished rats. However, bilateral inhibition of the shell also elicited increased locomotor activity. Nonetheless, unilateral inhibition of the accumbens shell did not increase motor activity, and simultaneous unilateral inactivation of the infralimbic cortex and shell induced cocaine seeking, suggesting that an interaction between these two structures is necessary for extinction training to inhibit cocaine seeking. The infralimbic cortex and accumbens shell appear to be recruited by extinction learning because inactivation of these structures prior to extinction training did not alter cocaine seeking. Together, these findings suggest that a neuronal network involving the infralimbic cortex and accumbens shell is recruited by extinction training to suppress cocaine seeking. PMID:18524910

  4. Infralimbic prefrontal cortex is responsible for inhibiting cocaine seeking in extinguished rats.

    PubMed

    Peters, Jamie; LaLumiere, Ryan T; Kalivas, Peter W

    2008-06-04

    The rat prelimbic prefrontal cortex and nucleus accumbens core are critical for initiating cocaine seeking. In contrast, the neural circuitry responsible for inhibiting cocaine seeking during extinction is unknown. The present findings using inhibition of selected brain nuclei with GABA agonists show that the suppression of cocaine seeking produced by previous extinction training required activity in the rat infralimbic cortex. Conversely, the reinstatement of drug seeking by a cocaine injection in extinguished animals was suppressed by increasing neuronal activity in infralimbic cortex with the glutamate agonist AMPA. The cocaine seeking induced by inactivating infralimbic cortex resembled other forms of reinstated drug seeking by depending on activity in prelimbic cortex and the basolateral amygdala. A primary efferent projection from the infralimbic cortex is to the nucleus accumbens shell. Akin to infralimbic cortex, inhibition of the accumbens shell induced cocaine seeking in extinguished rats. However, bilateral inhibition of the shell also elicited increased locomotor activity. Nonetheless, unilateral inhibition of the accumbens shell did not increase motor activity, and simultaneous unilateral inactivation of the infralimbic cortex and shell induced cocaine seeking, suggesting that an interaction between these two structures is necessary for extinction training to inhibit cocaine seeking. The infralimbic cortex and accumbens shell appear to be recruited by extinction learning because inactivation of these structures before extinction training did not alter cocaine seeking. Together, these findings suggest that a neuronal network involving the infralimbic cortex and accumbens shell is recruited by extinction training to suppress cocaine seeking.

  5. Neurons responsive to face-view in the Primate Ventrolateral Prefrontal Cortex

    PubMed Central

    Romanski, Lizabeth M.; Diehl, Maria M.

    2011-01-01

    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 non-human 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

  6. Remote effects of hypothalamic lesions in the prefrontal cortex of craniopharygioma patients.

    PubMed

    Ozyurt, Jale; Lorenzen, Anna; Gebhardt, Ursel; Warmuth-Metz, Monika; Müller, Hermann L; Thiel, Christiane M

    2014-05-01

    Albeit histologically low grade (WHO I(o)) brain tumors, craniopharyngiomas and/or their surgical removal frequently affect the hypothalamus, amongst other brain regions at risk. Due to rich hypothalamic connections with prefrontal and limbic regions, hypothalamic injury may adversely affect neural substrates of emotion processing and higher cognitive control, including memory and executive functions. The current study is the first to investigate the consequences of hypothalamic involvement on neural substrates of emotional and cognitive functioning. Ten patients with childhood craniopharyngioma and known hypothalamic involvement and fifteen age- and intelligence matched control subjects (median age: 17.8 and 17.3 yrs.) were studied with functional magnetic resonance imaging and an emotional face recognition task. During encoding, participants were asked to classify neutral and emotional faces. In a subsequent recognition phase, participants had to recognize these old faces within a set of new faces. Behavioral performance was comparable between patients and controls. Neural activity revealed, however, differential recruitment of fronto-limbic brain regions during recognition. Patients exhibited an abnormal pattern of task-induced activation and deactivation in the anterior and posterior rostral medial prefrontal cortex and a higher functional coupling between anterior rostral medial prefrontal cortex and the thalamus. Additionally, we found a higher reactivity in the patients' amygdala to emotional relative to neutral faces when compared to healthy controls. Our data provide first evidence that hypothalamic damage impacts neural correlates of memory retrieval in medial prefrontal cortex, indicating a less efficient use of an area involved in executive control processes. We propose that the deactivation failure in the patients' anterior rostral medial prefrontal cortex is related to an increased coupling with the thalamus and reflects a reduced efficiency to

  7. Reducing the Harm of Stress: Medications to Rescue the Prefrontal Cortex and Overcome Bad Habits

    PubMed Central

    Jin, Lu E.

    2011-01-01

    Our brain is sensitive to stress. Both acute and chronic stress cause cognitive deficits and induce chronic disorders such as drug addiction. In a June 2011 conference at Yale entitled “The Science of Stress: Focus on the Brain, Breaking Bad Habits, and Chronic Disease,” Drs. Amy Arnsten and Sherry Mckee discussed the roles of prefrontal cortex in the treatment of stress impairments and addiction. Medications to strengthen the prefrontal function, such as prazosin and guanfacine, may reduce the harm of stress and help overcome smoking and alcohol abuse. PMID:22180685

  8. 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.

    PubMed

    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.

  9. A combined TMS-EEG study of short-latency afferent inhibition in the motor and dorsolateral prefrontal cortex.

    PubMed

    Noda, Yoshihiro; Cash, Robin F H; Zomorrodi, Reza; Dominguez, Luis Garcia; Farzan, Faranak; Rajji, Tarek K; Barr, Mera S; Chen, Robert; Daskalakis, Zafiris J; Blumberger, Daniel M

    2016-09-01

    Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) enables noninvasive neurophysiological investigation of the human cortex. A TMS paradigm of short-latency afferent inhibition (SAI) is characterized by attenuation of the motor-evoked potential (MEP) and modulation of N100 of the TMS-evoked potential (TEP) when TMS is delivered to motor cortex (M1) following median nerve stimulation. SAI is a marker of cholinergic activity in the motor cortex; however, the SAI has not been tested from the prefrontal cortex. We aimed to explore the effect of SAI in dorsolateral prefrontal cortex (DLPFC). SAI was examined in 12 healthy subjects with median nerve stimulation and TMS delivered to M1 and DLPFC at interstimulus intervals (ISIs) relative to the individual N20 latency. SAI in M1 was tested at the optimal ISI of N20 + 2 ms. SAI in DLPFC was investigated at a range of ISI from N20 + 2 to N20 + 20 ms to explore its temporal profile. For SAI in M1, the attenuation of MEP amplitude was correlated with an increase of TEP N100 from the left central area. A similar spatiotemporal neural signature of SAI in DLPFC was observed with a marked increase of N100 amplitude. SAI in DLPFC was maximal at ISI N20 + 4 ms at the left frontal area. These findings establish the neural signature of SAI in DLPFC. Future studies could explore whether DLPFC-SAI is neurophysiological marker of cholinergic dysfunction in cognitive disorders. Copyright © 2016 the American Physiological Society.

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

    PubMed

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

    2005-01-01

    The aim of this study is to verify, after recovery, the presence of specific patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen patients with the diagnosis of TGA were submitted to a battery of neuropsyc